Background

Clinically, stiff person syndrome (SPS) is characterized by muscle rigidity that waxes and wanes with concurrent spasms.^{[1, 2]}Usually, it begins in the axial muscles and extends to the proximal limb muscles, but the severity of the limb muscle involvement may overwhelm the axial muscle involvement (stiff limb syndrome).^{[3, 4, 5, 6]}7 Some confusion has occurred as a result of cases that include other neurologic findings, such as encephalomyelitis, epilepsy, cerebral palsy, or cerebellar deficits, sometimes in addition to the classic clinical syndrome.^{[7, 8, 9, 10, 11, 12, 13]}

Stiff person syndrome is clinically classified into three main subtypes:

Classic stiff person syndrome (SPS):
- Characterized by progressive muscle stiffness and spasms, primarily affecting the axial muscles (trunk and proximal limbs).
- Symptoms worsen over time, leading to postural deformities such as hyperlordosis.
- Often associated with glutamic acid decarboxylase (GAD) antibodies.
Stiff limb syndrome (SLS):
- A variant that predominantly affects one or both limbs (typically the legs), leading to severe stiffness, spasms, and impaired mobility.
- Unlike classic SPS, the axial muscles are less involved.
- May later progress to involve additional muscle groups.
Progressive encephalomyelitis with rigidity and myoclonus (PERM):
- A severe and rapidly progressive form of SPS.^[14]
- Involves widespread muscle rigidity, myoclonus (sudden muscle jerks), brainstem dysfunction, and autonomic instability.

Duddy ME, Baker MR. Stiff person syndrome. Front Neurol Neurosci. 2009. 26:147-65. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Blum P, Jankovic J. Stiff-person syndrome: an autoimmune disease. Mov Disord. 1991. 6(1):12-20. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [Full Text].
Stayer C, Meinck HM. Stiff-man syndrome: an overview. Neurologia. 1998 Feb. 13(2):83-8. [QxMD MEDLINE Link].
Murinson BB. Stiff-person syndrome. Neurologist. 2004 May. 10(3):131-7. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Muranova A, Shanina E. Stiff Person Syndrome. 2025 Jan. [QxMD MEDLINE Link]. [Full Text].
Martinez-Hernandez E, Ariño 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 Jun 1. 73 (6):714-20. [QxMD MEDLINE Link].
Butler MH, Hayashi A, Ohkoshi N, et al. Autoimmunity to gephyrin in Stiff-Man syndrome. Neuron. 2000 May. 26(2):307-12. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Dalakas MC. Stiff person syndrome: advances in pathogenesis and therapeutic interventions. Curr Treat Options Neurol. 2009 Mar. 11(2):102-10. [QxMD MEDLINE Link].
Crane PD, Sillau S, Dreher R, Fix R, Winters P, Van Coevering R, et al. Population-Based Study of the Epidemiology of Stiff Person Syndrome in a Large Colorado-Based Health System. Neurology. 2024 Dec 24. 103 (12):e210078. [QxMD MEDLINE Link].
Hadavi S, Noyce AJ, Leslie RD, Giovannoni G. Stiff person syndrome. Pract Neurol. 2011 Oct. 11(5):272-82. [QxMD MEDLINE Link].
Ciccotto G, Blaya M, Kelley RE. Stiff person syndrome. Neurol Clin. 2013 Feb. 31(1):319-28. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [Full Text].
Newsome SD, Johnson T. Stiff person syndrome spectrum disorders; more than meets the eye. J Neuroimmunol. 2022 Aug 15. 369:577915. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Dalakas MC. Stiff-person syndrome and related disorders - diagnosis, mechanisms and therapies. Nat Rev Neurol. 2024 Oct. 20 (10):587-601. [QxMD MEDLINE Link].
Dalakas MC. Stiff Person Syndrome and GAD Antibody-Spectrum Disorders. Continuum (Minneap Minn). 2024 Aug 1. 30 (4):1110-1135. [QxMD MEDLINE Link].
Karlson EW, Sudarsky L, Ruderman E, Pierson S, Scott M, Helfgott SM. Treatment of stiff-man syndrome with intravenous immune globulin. Arthritis Rheum. 1994 Jun. 37 (6):915-8. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Pagano MB, Murinson BB, Tobian AA, King KE. Efficacy of therapeutic plasma exchange for treatment of stiff-person syndrome. Transfusion. 2014 Jul. 54 (7):1851-6. [QxMD MEDLINE Link].
Liguori R, Cordivari C, Lugaresi E, Montagna P. Botulinum toxin A improves muscle spasms and rigidity in stiff-person syndrome. Mov Disord. 1997 Nov. 12 (6):1060-3. [QxMD MEDLINE Link].

Media Gallery

of 0

#author-disclosures{display:block}#author-disclosures.modal-layer{position:relative}#author-disclosures .modal-content{max-height:none}#author-disclosures .close-modal{display:none}

Author

Nancy Theresa Rodgers-Neame, MD † Assistant Professor, Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine; Director, USF 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 Women's 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 in St Louis 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, CPE, MHCM, FAAPL Co-Founder and Former Chief Publishing Officer, eMedicine and eMedicine Health, Founding Editor-in-Chief, eMedicine Neurology; Founder and Former Chairman and CEO, Pearlsreview; Founder and CEO/CMO, PHLT Consultants; Former Chief Medical Officer, MeMD Inc

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

Disclosure: Nothing to disclose.

Additional Contributors

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

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

Disclosure: Nothing to disclose.

TOP PICKS FOR YOU

Stiff Person Syndrome

Background

References

Tables

Contributor Information and Disclosures

What would you like to print?