Stiff person syndrome, previously known as stiff man syndrome, is a very rare neuromuscular disease.
Onset is usually between 30 and 50 years of age. An association with autoimmune disease and various malignancies is described and these are thought to play a role in the pathophysiology.
Clinical presentation is characterized by:
- progressive muscle stiffness predominately affecting the axial muscles (especially the abdominal and thoracolumbar paraspinal musculature) and lower limbs
- muscle spasms triggered by external stimuli or emotional stress
- symptoms typically relieved by benzodiazepines
The diagnosis is usually confirmed with EMG and serology (anti-GAD and anti-amphiphysin antibodies). These are specific, however, they are only present in 60% of cases.
Stiff person syndrome is part of the spectrum of autoimmune encephalitides 4. Anti-GAD antibodies may bind to and lead to the progressive destruction of GABAergic neurons involved in motor pathways 2-4.
Additionally, a paraneoplastic syndrome causing anti-amphiphysin antibodies is described (the most common malignancies being breast followed by thymic, colorectal and lung tumors) 4.
Imaging is usually unremarkable 4. T2 hyperintensities of the brain and spinal cord on MRI have been described in a minority of case reports 4,5.
Treatment and prognosis
In addition to benzodiazepines, baclofen has been used for treatment. More recently, intravenous immunoglobulins (IVIG) have been used in combination with other drugs 3,4.
History and etymology
Stiff person syndrome was first described in 1956 by Moersch and Woltman of the Mayo Clinic 1.
- 1. Moersch FP, Woltman HW. 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. 2003;31 (15): 421-7. Pubmed citation
- 2. Solimena M, Folli F, Denis-Donini S et-al. Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy, and type I diabetes mellitus. N. Engl. J. Med. 1988;318 (16): 1012-20. doi:10.1056/NEJM198804213181602 - Pubmed citation
- 3. Karlson EW, Sudarsky L, Ruderman E et-al. Treatment of stiff-man syndrome with intravenous immune globulin. Arthritis Rheum. 1994;37 (6): 915-8. Pubmed citation
- 4. Sarva H, Deik A, Ullah A, Severt WL. Clinical Spectrum of Stiff Person Syndrome: A Review of Recent Reports. (2016) Tremor and other hyperkinetic movements (New York, N.Y.). 6: 340. doi:10.7916/D85M65GD - Pubmed
- 5. Byrne, Thomas N., Isakoff, Steven Jay, Rincon, Sandra P., Gudewicz, Thomas M.. Case 27-2012. (2012) The New England journal of medicine. 367 (9): 851-61. doi:10.1056/NEJMcpc1114036 - Pubmed