Stiff-Person Syndrome

  • Chafic KaramEmail author


Stiff person syndrome spectrum disorder (SPSSD) consists of a rare set of diseases characterized by severe muscle stiffness and rigidity with decline in function. Although poorly understood, an underlying autoimmune disorder interfering with the CNS inhibitory mechanism is likely the culprit. The spectrum ranges from a mild disease affecting focal muscles to a severe form that also includes the development of seizures and myoclonus.

 GAD-abs are frequently positive, especially in classic SPS. In SPS-plus/PERM, GlyR-abs are more commonly found. Patients with amphiphysin-ab should be screened for cancer. Treatment includes the GABA agonists, especially diazepam and baclofen. Patients with SPS-plus or refractory forms of the disease should be treated with immunomodulation, especially IVIG.


Stiff-person syndrome Stiff-person syndrome spectrum disorders (SPSSD) Autoimmune disease Muscle rigidity Classic SPS Stiff-limb syndrome SPS-plus Progressive encephalomyelitis with rigidity and myoclonus (PERM) Encephalomyelitis Seizures Myoclonus Diabetes mellitus Pernicious anemia Vitiligo Autoimmune thyroid disease DQB1∗0201 allele 


  1. 1.
    Pugliese A, Solimena M, Awdeh ZL, Alper CA, Bugawan T, Erlich HA, et al. Association of HLA-DQB1∗0201 with stiff-man syndrome. J Clin Endocrinol Metab. 1993;77(6):1550–3.PubMedGoogle Scholar
  2. 2.
    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. 1956;31(15):421–7.PubMedGoogle Scholar
  3. 3.
    Bowler D. The ‘stiff man syndrome’ in a boy. Arch Dis Child. 1960;35:289–92.CrossRefGoogle Scholar
  4. 4.
    Howard FM Jr. A new and effective drug in the treatment of the stiff-man syndrome: preliminary report. Proc Staff Meet Mayo Clin. 1963;38:203–12.PubMedGoogle Scholar
  5. 5.
    Lorish TR, Thorsteinsson G, Howard FM Jr. Stiff-man syndrome updated. Mayo Clin Proc. 1989;64(6):629–36.CrossRefGoogle Scholar
  6. 6.
    Blum P, Jankovic J. Stiff-person syndrome: an autoimmune disease. Mov Disord. 1991;6(1):12–20.CrossRefGoogle Scholar
  7. 7.
    Martinez-Hernandez E, Arino H, McKeon A, Iizuka T, Titulaer MJ, Simabukuro MM, et al. Clinical and immunologic investigations in patients with stiff-person spectrum disorder. JAMA Neurol. 2016;73(6):714–20.CrossRefGoogle Scholar
  8. 8.
    Solimena M, Folli F, Denis-Donini S, Comi GC, Pozza G, De Camilli P, 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.CrossRefGoogle Scholar
  9. 9.
    Solimena M, Folli F, Aparisi R, Pozza G, De Camilli P. Autoantibodies to GABA-ergic neurons and pancreatic beta cells in stiff-man syndrome. N Engl J Med. 1990;s322(22):1555–60.CrossRefGoogle Scholar
  10. 10.
    Dinkel K, Meinck HM, Jury KM, Karges W, Richter W. Inhibition of gamma-aminobutyric acid synthesis by glutamic acid decarboxylase autoantibodies in stiff-man syndrome. Ann Neurol. 1998;44(2):194–201.CrossRefGoogle Scholar
  11. 11.
    Turner MR, Irani SR, Leite MI, Nithi K, Vincent A, Ansorge O. Progressive encephalomyelitis with rigidity and myoclonus: glycine and NMDA receptor antibodies. Neurology. 2011;77(5):439–43.CrossRefGoogle Scholar
  12. 12.
    Butler MH, Hayashi A, Ohkoshi N, Villmann C, Becker CM, Feng G, et al. Autoimmunity to gephyrin in stiff-man syndrome. Neuron. 2000;26(2):307–12.CrossRefGoogle Scholar
  13. 13.
    Sommer C, Weishaupt A, Brinkhoff J, Biko L, Wessig C, Gold R, et al. Paraneoplastic stiff-person syndrome: passive transfer to rats by means of igg antibodies to amphiphysin. Lancet. 2005;365(9468):1406–11.CrossRefGoogle Scholar
  14. 14.
    McKeon A, Robinson MT, McEvoy KM, Matsumoto JY, Lennon VA, Ahlskog JE, et al. Stiff-man syndrome and variants: clinical course, treatments, and outcomes. Arch Neurol. 2012;69(2):230–8.CrossRefGoogle Scholar
  15. 15.
    Meinck HM, Thompson PD. Stiff man syndrome and related conditions. Mov Disord. 2002;17(5):853–66.CrossRefGoogle Scholar
  16. 16.
    Economides JR, Horton JC. Eye movement abnormalities in stiff person syndrome. Neurology. 2005;65(9):1462–4.CrossRefGoogle Scholar
  17. 17.
    Oskarsson B, Pelak V, Quan D, Hall D, Foster C, Galetta S. Stiff eyes in stiff-person syndrome. Neurology. 2008;71(5):378–80.CrossRefGoogle Scholar
  18. 18.
    Brown P, Rothwell JC, Marsden CD. The stiff leg syndrome. J Neurol Neurosurg Psychiatry. 1997;62(1):31–7.CrossRefGoogle Scholar
  19. 19.
    Barker RA, Revesz T, Thom M, Marsden CD, Brown P. Review of 23 patients affected by the stiff man syndrome: clinical subdivision into stiff trunk (man) syndrome, stiff limb syndrome, and progressive encephalomyelitis with rigidity. J Neurol Neurosurg Psychiatry. 1998;65(5):633–40.CrossRefGoogle Scholar
  20. 20.
    Rakocevic G, Raju R, Semino-Mora C, Dalakas MC. Stiff person syndrome with cerebellar disease and high-titer anti-GAD antibodies. Neurology. 2006;67(6):1068–70.CrossRefGoogle Scholar
  21. 21.
    Carvajal-Gonzalez A, Leite MI, Waters P, Woodhall M, Coutinho E, Balint B, et al. Glycine receptor antibodies in perm and related syndromes: characteristics, clinical features and outcomes. Brain. 2014;137(Pt 8):2178–92.CrossRefGoogle Scholar
  22. 22.
    Dayalu P, Teener JW. Stiff person syndrome and other anti-GAD-associated neurologic disorders. Semin Neurol. [Case Reports Review]. 2012;32(5):544–9.CrossRefGoogle Scholar
  23. 23.
    Saiz A, Blanco Y, Sabater L, Gonzalez F, Bataller L, Casamitjana R, et al. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain. 2008;131(Pt 10):2553–63.CrossRefGoogle Scholar
  24. 24.
    McKeon A, Martinez-Hernandez E, Lancaster E, Matsumoto JY, Harvey RJ, McEvoy KM, et al. Glycine receptor autoimmune spectrum with stiff-man syndrome phenotype. JAMA Neurol. 2013;70(1):44–50.CrossRefGoogle Scholar
  25. 25.
    Murinson BB, Guarnaccia JB. Stiff-person syndrome with amphiphysin antibodies: distinctive features of a rare disease. Neurology. 2008;71(24):1955–8.CrossRefGoogle Scholar
  26. 26.
    McKeon A, Pittock SJ, Lennon VA. Stiff-person syndrome with amphiphysin antibodies: distinctive features of a rare disease. Neurology. 2009;73(24):2132; author reply 2133.CrossRefGoogle Scholar
  27. 27.
    Floeter MK, Valls-Sole J, Toro C, Jacobowitz D, Hallett M. Physiologic studies of spinal inhibitory circuits in patients with stiff-person syndrome. Neurology. 1998;51(1):85–93.CrossRefGoogle Scholar
  28. 28.
    Matsumoto JY, Caviness JN, McEvoy KM. The acoustic startle reflex in stiff-man syndrome. Neurology. 1994;44(10):1952–5.CrossRefGoogle Scholar
  29. 29.
    Dalakas MC. Intravenous immunoglobulin in patients with anti-GAD antibody-associated neurological diseases and patients with inflammatory myopathies: effects on clinicopathological features and immunoregulatory genes. Clin Rev Allergy Immunol. 2005;29(3):255–69.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.ALS and Neuromuscular Disease Center, Department of NeurologyOregon Health & Science UniversityPortlandUSA

Personalised recommendations