Medscape is available in 5 Language Editions – Choose your Edition here.


Stiff Person Syndrome Differential Diagnoses

  • Author: Nancy Theresa Rodgers-Neame, MD; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
Updated: May 05, 2016

Diagnostic Considerations

Painful tonic spasms of multiple sclerosis

Hereditary hyperekplexia

Idiopathic hyperekplexia

Cocaine-addicted infant

Startle syndrome

Hereditary startle disease

Stiff encephalomyelitis

Paraneoplastic hypertonic syndrome


Somatoform disorder

Myoclonic seizures

Axial torsion dystonia

Neuromyotonia (Isaac syndrome)

Schwartz-Jampel syndrome

Differential Diagnoses

Contributor Information and Disclosures

Nancy Theresa Rodgers-Neame, MD Assistant Professor, Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine; Director, Florida Comprehensive Epilepsy and Seizure Disorders Program

Nancy Theresa Rodgers-Neame, MD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Womens Association, Society for Neuroscience, Southern Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Glenn Lopate, MD Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Consulting Staff, Department of Neurology, Barnes-Jewish Hospital

Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, Phi Beta Kappa

Disclosure: Nothing to disclose.

Chief Editor

Nicholas Lorenzo, MD, MHA, CPE Founding Editor-in-Chief, eMedicine Neurology; Founder and CEO/CMO, PHLT Consultants; Chief Medical Officer, MeMD Inc

Nicholas Lorenzo, MD, MHA, CPE is a member of the following medical societies: Alpha Omega Alpha, American Association for Physician Leadership, American Academy of Neurology

Disclosure: Nothing to disclose.

Additional Contributors

Paul E Barkhaus, MD Professor of Neurology and Physical Medicine and Rehabilitation, Department of Neurology, Medical College of Wisconsin; Section Chief, Neuromuscular and Autonomic Disorders, Department of Neurology, Director, ALS Program, Medical College of Wisconsin

Paul E Barkhaus, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

  1. Hadavi S, Noyce AJ, Leslie RD, Giovannoni G. Stiff person syndrome. Pract Neurol. 2011 Oct. 11(5):272-82. [Medline].

  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. Mayo Clin Proc. 1956. 31:421-7.

  3. Duddy ME, Baker MR. Stiff person syndrome. Front Neurol Neurosci. 2009. 26:147-65. [Medline].

  4. Misra UK, Maurya PK, Kalita J, Gupta RK. Stiff limb syndrome: end of spectrum or a separate entity?. Pain Med. 2009 Apr. 10(3):594-7. [Medline].

  5. Blum P, Jankovic J. Stiff-person syndrome: an autoimmune disease. Mov Disord. 1991. 6(1):12-20. [Medline].

  6. Dalakas MC, Fujii M, Li M, McElroy B. The clinical spectrum of anti-GAD antibody-positive patients with stiff-person syndrome. Neurology. 2000 Nov 28. 55(10):1531-5. [Medline]. [Full Text].

  7. Stayer C, Meinck HM. Stiff-man syndrome: an overview. Neurologia. 1998 Feb. 13(2):83-8. [Medline].

  8. Murinson BB. Stiff-person syndrome. Neurologist. 2004 May. 10(3):131-7. [Medline].

  9. Jimenez Caballero PE. Stiff person syndrome: presentation of a case with repetitive complex discharges in electromiograms. Neurologist. 2009 Jul. 15(4):227-9. [Medline].

  10. 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 Nov. 65(5):633-40. [Medline].

  11. Ishida K, Mitoma H, Song SY, et al. Selective suppression of cerebellar GABAergic transmission by an autoantibody to glutamic acid decarboxylase. Ann Neurol. 1999 Aug. 46(2):263-7. [Medline].

  12. Lenti C, Bognetti E, Bonfanti R, Bonifacio E, Meschi F. Myoclonic encephalopathy and diabetes mellitus in a boy. Dev Med Child Neurol. 1999 Jul. 41(7):489-90. [Medline].

  13. Mitoma H, Song SY, Ishida K, Yamakuni T, Kobayashi T, Mizusawa H. Presynaptic impairment of cerebellar inhibitory synapses by an autoantibody to glutamate decarboxylase. J Neurol Sci. 2000 Apr 1. 175(1):40-4. [Medline].

  14. Lynex CN, Carr IM, Leek JP, et al. Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders. BMC Neurol. 2004 Nov 30. 4(1):20. [Medline].

  15. Peltola J, Kulmala P, Isojarvi J, et al. Autoantibodies to glutamic acid decarboxylase in patients with therapy-resistant epilepsy. Neurology. 2000 Jul 12. 55(1):46-50. [Medline].

  16. Aso Y, Sato A, Narimatsu M, et al. Stiff-man syndrome associated with antecedent myasthenia gravis and organ-specific autoimmunopathy. Intern Med. 1997 Apr. 36(4):308-11. [Medline].

  17. Ellis TM, Atkinson MA. The clinical significance of an autoimmune response against glutamic acid decarboxylase. Nat Med. 1996 Feb. 2(2):148-53. [Medline].

  18. 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 Aug. 44(2):194-201. [Medline].

  19. Butler MH, Solimena M, Dirkx R Jr, Hayday A, De Camilli P. Identification of a dominant epitope of glutamic acid decarboxylase (GAD-65) recognized by autoantibodies in stiff-man syndrome. J Exp Med. 1993 Dec 1. 178(6):2097-106. [Medline].

  20. Dalakas MC, Li M, Fujii M, Jacobowitz DM. Stiff person syndrome: quantification, specificity, and intrathecal synthesis of GAD65 antibodies. Neurology. 2001 Sep 11. 57(5):780-4. [Medline].

  21. Lernmark A. Glutamic acid decarboxylase--gene to antigen to disease. J Intern Med. 1996 Nov. 240(5):259-77. [Medline].

  22. O'Sullivan EP, Behan LA, King TF, Hardiman O, Smith D. A case of stiff-person syndrome, type 1 diabetes, celiac disease and dermatitis herpetiformis. Clin Neurol Neurosurg. 2009 May. 111(4):384-6. [Medline].

  23. Geis C, Beck M, Jablonka S, et al. Stiff person syndrome associated anti-amphiphysin antibodies reduce GABA associated [Ca(2+)](i) rise in embryonic motoneurons. Neurobiol Dis. 2009 Jul 23. [Medline].

  24. Butler MH, Hayashi A, Ohkoshi N, et al. Autoimmunity to gephyrin in Stiff-Man syndrome. Neuron. 2000 May. 26(2):307-12. [Medline].

  25. Dalakas MC. Stiff person syndrome: advances in pathogenesis and therapeutic interventions. Curr Treat Options Neurol. 2009 Mar. 11(2):102-10. [Medline].

  26. Levy LM, Dalakas MC, Floeter MK. The stiff-person syndrome: an autoimmune disorder affecting neurotransmission of gamma-aminobutyric acid. Ann Intern Med. 1999 Oct 5. 131(7):522-30. [Medline]. [Full Text].

  27. Ziegler B, Strebelow M, Rjasanowski I, Schlosser M, Ziegler M. A monoclonal antibody-based characterization of autoantibodies against glutamic acid decarboxylase in adults with latent autoimmune diabetes. Autoimmunity. 1998. 28(2):61-8. [Medline].

  28. Hadavi S, Noyce AJ, Leslie RD, Giovannoni G. Stiff person syndrome. Pract Neurol. 2011 Oct. 11(5):272-82. [Medline].

  29. Ciccoto G, Blaya M, Kelley RE. Stiff person syndrome. Neurol Clin. 2013 Feb. 31(1):319-28. [Medline].

  30. Sarva H, Deik A, Ullah A, Severt WL. Clinical Spectrum of Stiff Person Syndrome: A Review of Recent Reports. Tremor Other Hyperkinet Mov (N Y). 2016. 6:340. [Medline].

  31. Bhatti AB, Gazali ZA. Recent Advances and Review on Treatment of Stiff Person Syndrome in Adults and Pediatric Patients. Cureus. 2015 Dec 22. 7 (12):e427. [Medline].

  32. Rakocevic G, Floeter MK. Autoimmune stiff person syndrome and related myelopathies: understanding of electrophysiological and immunological processes. Muscle Nerve. 2012 May. 45(5):623-34. [Medline]. [Full Text].

  33. Hayashi A, Nakamagoe K, Ohkoshi N, Hoshino S, Shoji S. Double filtration plasma exchange and immunoadsorption therapy in a case of stiff-man syndrome with negative anti-GAD antibody. J Med. 1999. 30(5-6):321-7. [Medline].

  34. Goldkamp J, Blaskiewicz R, Myles T. Stiff person syndrome and pregnancy. Obstet Gynecol. 2011 Aug. 118(2 Pt 2):454-7. [Medline].

  35. Brashear HR, Phillips LH 2nd. Autoantibodies to GABAergic neurons and response to plasmapheresis in stiff-man syndrome. Neurology. 1991 Oct. 41(10):1588-92. [Medline].

  36. Brown P, Rothwell JC, Marsden CD. The stiff leg syndrome. J Neurol Neurosurg Psychiatry. 1997 Jan. 62(1):31-7. [Medline].

  37. Culav- Sumic J, Bosnjak I, Pastar Z, Jukic V. Anxious depression and the stiff-person plus syndrome. Cogn Behav Neurol. 2008 Dec. 21(4):242-5.

  38. 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 Dec. 29(3):255-69. [Medline].

  39. Daw K, Ujihara N, Atkinson M, Powers AC. Glutamic acid decarboxylase autoantibodies in stiff-man syndrome and insulin-dependent diabetes mellitus exhibit similarities and differences in epitope recognition. J Immunol. 1996 Jan 15. 156(2):818-25. [Medline].

  40. De Camilli P, Thomas A, Cofiell R, et al. The synaptic vesicle-associated protein amphiphysin is the 128-kD autoantigen of Stiff-Man syndrome with breast cancer. J Exp Med. 1993 Dec 1. 178(6):2219-23. [Medline].

  41. Fiol M, Cammarota A, Rivero A, Pardal A, Nogues M, Correale J. Focal stiff-person syndrome. Neurologia. 2001 Feb. 16(2):89-91. [Medline].

  42. Floyd S, Butler MH, Cremona O, et al. Expression of amphiphysin I, an autoantigen of paraneoplastic neurological syndromes, in breast cancer. Mol Med. 1998 Jan. 4(1):29-39. [Medline].

  43. Gerschlager W, Schrag A, Brown P. Quality of life in stiff-person syndrome. Mov Disord. 2002 Sep. 17(5):1064-7. [Medline].

  44. Goppert D, Gardill K, Beischer W, Wietholter H. [The stiff-man syndrome with diabetes mellitus type 1 and autoimmune thyroiditis]. Dtsch Med Wochenschr. 2000 Jul 7. 125(27):826-9. [Medline].

  45. Johnstone AP, Nussey SS. Direct evidence for limited clonality of antibodies to glutamic acid decarboxylase (GAD) in stiff man syndrome using baculovirus expressed GAD. J Neurol Neurosurg Psychiatry. 1994 May. 57(5):659. [Medline].

  46. Lohmann T, Hawa M, Leslie RD, Lane R, Picard J, Londei M. Immune reactivity to glutamic acid decarboxylase 65 in stiffman syndrome and type 1 diabetes mellitus. Lancet. 2000 Jul 1. 356(9223):31-5. [Medline].

  47. Martino G, Grimaldi LM, Bazzigaluppi E, Passini N, Sinigaglia F, Rogge L. The insulin-dependent diabetes mellitus-associated ICA 105 autoantigen in stiff-man syndrome patients. J Neuroimmunol. 1996 Sep. 69(1-2):129-34. [Medline].

  48. Meinck HM, Ricker K, Hulser PJ, Schmid E, Peiffer J, Solimena M. Stiff man syndrome: clinical and laboratory findings in eight patients. J Neurol. 1994 Jan. 241(3):157-66. [Medline].

  49. Nicholas AP, Chatterjee A, Arnold MM, Claussen GC, Zorn GL Jr, Oh SJ. Stiff-persons' syndrome associated with thymoma and subsequent myasthenia gravis. Muscle Nerve. 1997 Apr. 20(4):493-8. [Medline].

  50. Raju R, Foote J, Banga JP, et al. Analysis of GAD65 autoantibodies in Stiff-Person syndrome patients. J Immunol. 2005 Dec 1. 175(11):7755-62. [Medline].

  51. Saravanan PK, Paul J, Sayeed ZA. Stiff person syndrome and myasthenia gravis. Neurol India. 2002 Mar. 50(1):98-100. [Medline].

  52. Shariatmadar S, Noto TA. Plasma exchange in stiff-man syndrome. Ther Apher. 2001 Feb. 5(1):64-7. [Medline].

  53. Solimena M, Butler MH, De Camilli P. GAD, diabetes, and Stiff-Man syndrome: some progress and more questions. J Endocrinol Invest. 1994 Jul-Aug. 17(7):509-20. [Medline].

  54. Solimena M, De Camilli P. Autoimmunity to glutamic acid decarboxylase (GAD) in Stiff-Man syndrome and insulin-dependent diabetes mellitus. Trends Neurosci. 1991 Oct. 14(10):452-7. [Medline].

  55. 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 Apr 16-22. 365(9468):1406-11. [Medline].

  56. Takenoshita H, Shizuka-Ikeda M, Mitoma H, et al. Presynaptic inhibition of cerebellar GABAergic transmission by glutamate decarboxylase autoantibodies in progressive cerebellar ataxia. J Neurol Neurosurg Psychiatry. 2001 Mar. 70(3):386-9. [Medline]. [Full Text].

  57. Vincent A, Grimaldi LM, Martino G, Davenport C, Todd I. Antibodies to 125I-glutamic acid decarboxylase in patients with stiff man syndrome. J Neurol Neurosurg Psychiatry. 1997 Apr. 62(4):395-7. [Medline].

  58. Warich-Kirches M, Von Bossanyi P, Treuheit T, et al. Stiff-man syndrome: possible autoimmune etiology targeted against GABA-ergic cells. Clin Neuropathol. 1997 Jul-Aug. 16(4):214-9. [Medline].

All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.