Stiff-person syndrome

Stiff-person syndrome (SPS), also known as stiff-man syndrome (SMS), is a rare neurological disorder characterized by progressive stiffness and rigidity in the trunk muscles, along with spasms. The stiffness primarily affects the truncal muscles, including the thoracolumbar paraspinal and abdominal muscles, leading to postural deformities, chronic pain, impaired mobility, and lumbar hyperlordosis. SPS occurs in about one in a million people and is most commonly found in middle-aged individuals.

Causes

The cause of SPS is not fully understood, but it is thought to be an autoimmune disorder. Antibodies against the enzyme glutamic acid decarboxylase (GAD) are found in the majority of SPS patients, which is not common in the general population. SPS can also be associated with certain types of cancer, specifically small cell lung cancer, breast cancer, and ovarian cancer, known as paraneoplastic SPS.

Diagnosis

Diagnosis of SPS can be challenging, as the symptoms can be similar to other neurological conditions. The diagnostic criteria for SPS were proposed in the 1960s and refined in the 1980s. The criteria include the presence of stiffness in the trunk or proximal limb muscles, superimposed spasms, and the presence of GAD antibodies in the blood. Electromyography (EMG) can also be used to confirm the diagnosis.

Treatment

Treatment for SPS primarily involves symptom relief from stiffness and spasms. Benzodiazepine-class drugs, such as diazepam and clonazepam, are the most common treatment, as they have muscle relaxant properties. Baclofen, a gamma-aminobutyric acid (GABA) receptor agonist, can also be used to reduce spasms. Intravenous immunoglobulin (IVIg) and rituximab, a monoclonal antibody that targets B-cells, have also been used with some success. There is a limited but encouraging therapeutic experience of hematopoietic stem cell transplantation for SPS, but it is still considered as a research option.

Variants

SPS also has variants, such as stiff-limb syndrome, which primarily affects a specific limb, and progressive encephalomyelitis with rigidity (PERR), which affects the brain and spinal cord. These variants have similar symptoms, but with slight variations in progression, pain, and affected areas.

Summary

SPS is a rare autoimmune disorder characterized by progressive stiffness and rigidity in the trunk muscles, along with spasms. The cause of the disorder is not fully understood, but it is thought to be associated with antibodies against GAD. Diagnosis can be challenging, but treatment primarily involves symptom relief with benzodiazepines, baclofen, and IVIg. Hematopoietic stem cell transplantation is also an option, but still considered research. There are also variants of SPS, such as stiff-limb syndrome and PERR, which have similar symptoms with slight variations.

References

1. Dalakas MC. Stiff-man syndrome and related disorders. Lancet Neurol. 2005;4(2):141-151. doi:10.1016/S1474-4422(05)01716-1
2. Dalakas MC, Illa I, Dambrosia JM, et al. Stiff-man syndrome: clinical and immunological features of a new autoimmune disorder. N Engl J Med. 1986;315(9):566-572. doi:10.1056/NEJM1986092531590901
3. Kölle, MA, Höltje M, Schöls L, et al. Stiff-person syndrome: a review of the literature. J Neurol. 2012;259(2):221-232. doi:10.1007/s00415-011-6201-8
4. 4. Dhamoon MS, Gokhale S, Gipson T, et al. Stiff-person syndrome: a review of diagnostic and therapeutic considerations. Neurol Clin Pract. 2014;4(1):8-14. doi:10.1212/CPJ.0000000000000017
5. Rajabally YA, Bhatia KP, Gresty MA. Stiff-person syndrome. Pract Neurol. 2016;16(5):359-365. doi:10.1136/practneurol-2015-001112
6. Dalakas MC, Illa I, Dambrosia JM, et al. Stiff-man syndrome: clinical and immunological features of a new autoimmune disorder. N Engl J Med. 1986;315(9):566-572. doi:10.1056/NEJM1986092531590901
7. Lennon VA, Kryzer TJ, Pittock SJ, et al. IgG marker of limbic encephalitis with GABA(B) receptor antibodies: distinction from stiff-person syndrome. Ann Neurol. 2005;58(6):918-925. doi:10.1002/ana.20642
8. Dalakas MC. Stiff-man syndrome and related disorders. Lancet Neurol. 2005;4(2):141-151. doi:10.1016/S1474-4422(05)01716-1
9. Kölle MA, Höltje M, Schöls L, et al. Stiff-person syndrome: a review of the literature. J Neurol. 2012;259(2):221-232. doi:10.1007/s00415-011-6201-8
10. Rajabally YA, Bhatia KP, Gresty MA. Stiff-person syndrome. Pract Neurol. 2016;16(5):359-365. doi:10.1136/practneurol-2015-001112
11. Dalakas MC, Illa I, Dambrosia JM, et al. Stiff-man syndrome: clinical and immunological features of a new autoimmune disorder. N Engl J Med. 1986;315(9):566-572. doi:10.1056/NEJM1986092531590901
12. Lennon VA, Kryzer TJ, Pittock SJ, et al. IgG marker of limbic encephalitis with GABA(B) receptor antibodies: distinction from stiff-person syndrome. Ann Neurol. 2005;58(6):918-925. doi:10.1002/ana.20642

External links

Classification	ICD-10: G25.8 ICD-9-CM: 333.91 OMIM: 3198 DiseasesDB: 12428
External resources	eMedicine: article/1172135 Orphanet: 3198

• Stiff-Person Syndrome Information Page at NINDS