Stiffness-person syndrome (SPS), also known by the name of Moersch-Woltman syndrome, is a rare central nervous system disease characterized by inflexibility and oscillating painful muscle contractions.They are known to be triggered by external stimuli (tactile stimulus, stress, loud noise). The primary group of muscles involved in this condition are the axial and proximal limb muscles. Stiffness can be attributed to the co-activation of the agonist and antagonist muscles. Progressive stiffness results in difficulty walking, severe impairment and significant co-morbidities.
SPS has an autoimmune etiology. The classical variant is associated with anti-glutamic acid decarboxylase antibodies (anti-GAD). This high levels of anti-GAD antibody titres causes impaired inhibitory GABAergic neurotransmission. This leads to an incomplete relaxation of the axial and proximal muscle groups due to over-excitability of the motor cortex in the brain. SPS can be associated with other autoimmune conditions such as Type 1 Diabetes mellitus, vitiligo and celiac disease.
SPS can be classified into three variants: the classical, the partial and progressive encephalomyelitis with rigidity and myoclonus (PERM). Persistent muscle stiffness of the abdominal muscles can lead to difficulty in maintaining posture and axial movement. A patient may also experience recurrent falls and lumbar hyperlordoises. Chronic muscle pain is also a common manifestation. Proximal limb muscle rigidity can lead to extreme hindrance to walking, ultimately leading to complete its cessation. Associated conditions include neuropsychiatric illnesses, such as anxiety and depression. Rare complications include hyperreflexia, nystagmus, vertical gaze palsy, and dystonia.
The accepted criteria for the clinical diagnoses of SPS is the Dalakas criteria, which includes:
Stiffness of the limb and axial muscles, especially in the abdominal and thoraco-lumbar region, leading to hyperloirdosis, difficulty bending and gait abnormalities.
Presence of painful muscle spasms triggered by an external stimulus (tactile or auditory)
EMG finding of continuous motor unit activity in agonist and antagonist muscles despite relaxation efforts
Absence of other neurological manifestations that point out alternative diagnoses
High serum anti-GAD antibody titre levels (more than 10,000 IU/mL)
Clinical response to benzodiazepenes
Electro-diagnostic studies are done to rule out other nerve and muscle pathologies. Needle electromyography shows involuntary motor unit activity even at rest, despite measures to induce relaxation. MRI of brain and spine are also done to rule out other cranial pathologies.
To confirm a paraneoplastic variant, antibody levels of anti-amphiphysin and anti-gephryin is done. Tests to identify the presence of a co-existing autoimmune condition or malignancy is also carried out to confirm the underlying cause.
Management of SPS is divided into two broad domains: symptomatic and pharmacological. Muscle stiffness, rigidity, spasms are managed with medications such as diazepam, botulinum toxin, benzodiazepenes, baclofen (anti-spasmodic), and gabapentin (anti-convulsant) [8]. These drugs promote the activity of GABA. Muscle relaxants such as dantrolene and tizanidine are also used. Antidepressants and anti-anxiety medications are prescribed to manage the co-existing psychiatric illnesses.
Disease specific treatment includes immunotherapy, that aims at reducing the high circulating antibody levels in the patient’s serum. Intravenous immunoglobulin (IVIG), is the current most effective option for SPS, proving significant improvement after five doses.
Ongoing research on the effectiveness of plasma exchange therapy, corticosteroids, rituximab (monoclonal antibody against CD-20 antigen on B-cells), azathioprine, cyclophosphamide, tacrolimus, mycophenolate mofetil is being conducted.
Physical therapy and home exercise regimens play a vital role in managing Stiff Person Syndrome (SPS) by promoting flexibility and mobility. Tailored exercises targeting affected muscle groups can help alleviate stiffness and improve functional ability.
Stiff-person syndrome is a rare disorder which consists of an autoimmune component as a part of its underlying pathogenesis. Like every other autoimmune disorder, the symptoms can be alleviated through supportive management that significantly improves the quality of life of a patient. However, definitive management can not only provide comfort, but also exhibit long term benefits in its successful complete cessation of symptoms.
References:
1. Muranova, A., & Shanina, E. (2023, July 10). Stiff Person Syndrome. In StatPearls. Treasure Island, FL: StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK573078
2. Buechner, S., Florio, I., & Capone, L. (2015). Stiff Person Syndrome: A Rare Neurological Disorder, Heterogeneous in Clinical Presentation and Not Easy to Treat. Case Rep Neurol Med, 2015, 278065. https://doi.org/10.1155/2015/278065
3. Dalakas, M. C. (2023). Therapies in Stiff-Person Syndrome: Advances and Future Prospects Based on Disease Pathophysiology. Neurol Neuroimmunol Neuroinflamm, 10(3), e200109. https://doi.org/10.1212/NXI.0000000000200109
4. Trujillo, F. G., Cortes, K. P., Arrazole, G. B., et al. (2020). Stiff person syndrome, clinical case presentation and treatment update. Revista Colombiana de Reumatología, 27(2), 130-134. https://doi.org/10.1016/j.rcreue.2019.02.005
5. Ortiz, J. F., Ghani, M. R., Morillo Cox, Á., Tambo, W., Bashir, F., Wirth, M., & Moya, G. (2020, December 9). Stiff-Person Syndrome: A Treatment Update and New Directions. Cureus, 12(12), e11995. https://doi.org/10.7759/cureus.11995
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