Medical Care

Initial medical treatment may involve either baclofen or a benzodiazepine.^[3]Although no studies have been performed, tizanidine (Zanaflex) may be a less sedating alternative. Other medications that have been tried include antiepileptic medications, dantrolene, and barbiturates, but no clinical trials have been performed.

Intrathecal baclofen therapy
- Some patients may be candidates for intrathecal baclofen therapy for long-term treatment. Because symptoms may be variable, an externally programmable pump may be the best option.
- Evaluation for intrathecal baclofen therapy by an experienced evaluator, the neurosurgeon involved, and the neurologist caring for the patient should coordinate the procedure so that the goals of therapy are clear. Deaths have been reported in stiff person syndrome from baclofen pump failure; share this fact with the team and the patient. Baclofen pump therapy should not be considered the sole therapy for the disease.
Plasmapheresis (plasma exchange)
- In some patients, plasmapheresis has been demonstrated to be of clinical utility in the treatment of stiff person syndrome.^[34]
- No real prescribed dosage exists for plasmapheresis. The time of plasmapheresis, amount of supplementary albumin, and other parameters are controlled on a patient-by-patient basis by the pathologist running the blood bank involved in the procedure. A 5-treatment series administered every other day is considered a standard regimen for autoimmune diseases, but longer and shorter regimens have been used.
- The efficacy is then evaluated and further treatment is decided on a patient-by-patient basis, usually as a collaborative effort with the insurance company physicians because it is such an expensive procedure.
- Possible adverse effects include hypotension, bleeding, arrhythmias, and infection.
Intravenous immunoglobulin
- Intravenous immunoglobulin (IVIG) has also been used in the inpatient setting for the treatment of stiff person syndrome. The usual dose is 2 g/kg, administered over 2-5 days.
- The length of the series is variable and dependent upon patient response. Treatment may extend past the inpatient period.^[26](Documentation of patient response is usually necessary for ongoing reimbursement by third party payers.)
- Remember that IVIG is contraindicated in patients with IgA deficiency because of increased anaphylaxis in these patients.
Physical therapy and occupational therapy
- Physical therapy and occupational therapy are critical to the recovery of the patient under treatment. Medical treatment may make the patient feel weak, a feeling that may respond well to therapy.
- The patient may also have a great deal of problems with voluntary movement and fine motor skills.

Consultations

Psychiatry may be consulted especially when symptoms of depression or anxiety are prominent. The psychiatrist should be made aware of the pathophysiology of stiff person syndrome and that the anxiety symptoms may be directly related to the presence of glutamic acid decarboxylase antibodies in the central nervous system. If possible, consult a psychiatrist that has shown interest in the disease.

Activity

Exercise or physical therapy may be helpful in preserving range of motion and in relieving symptoms related to prolonged muscle tension. In addition, muscular biofeedback may be helpful, although careful studies of physical therapy treatments have not been done. Keep in mind that activity or exercise may exacerbate spasms.

Medication

Hadavi S, Noyce AJ, Leslie RD, Giovannoni G. Stiff person syndrome. Pract Neurol. 2011 Oct. 11(5):272-82. [QxMD MEDLINE Link].
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.
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].
Jimenez Caballero PE. Stiff person syndrome: presentation of a case with repetitive complex discharges in electromiograms. Neurologist. 2009 Jul. 15(4):227-9. [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].
Ellis TM, Atkinson MA. The clinical significance of an autoimmune response against glutamic acid decarboxylase. Nat Med. 1996 Feb. 2(2):148-53. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [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].
Lernmark A. Glutamic acid decarboxylase--gene to antigen to disease. J Intern Med. 1996 Nov. 240(5):259-77. [QxMD MEDLINE Link].
Baizabal-Carvallo JF, Jankovic J. Autoimmune and paraneoplastic movement disorders: An update. J Neurol Sci. 2018 Feb 15. 385:175-184. [QxMD MEDLINE Link].
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. [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].
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].
Dalakas MC. Stiff person syndrome: advances in pathogenesis and therapeutic interventions. Curr Treat Options Neurol. 2009 Mar. 11(2):102-10. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [Full Text].
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. [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].
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].
Goldkamp J, Blaskiewicz R, Myles T. Stiff person syndrome and pregnancy. Obstet Gynecol. 2011 Aug. 118(2 Pt 2):454-7. [QxMD MEDLINE Link].
Brashear HR, Phillips LH 2nd. Autoantibodies to GABAergic neurons and response to plasmapheresis in stiff-man syndrome. Neurology. 1991 Oct. 41(10):1588-92. [QxMD MEDLINE Link].
Brown P, Rothwell JC, Marsden CD. The stiff leg syndrome. J Neurol Neurosurg Psychiatry. 1997 Jan. 62(1):31-7. [QxMD MEDLINE Link].
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.
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Fiol M, Cammarota A, Rivero A, Pardal A, Nogues M, Correale J. Focal stiff-person syndrome. Neurologia. 2001 Feb. 16(2):89-91. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Gerschlager W, Schrag A, Brown P. Quality of life in stiff-person syndrome. Mov Disord. 2002 Sep. 17(5):1064-7. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Saravanan PK, Paul J, Sayeed ZA. Stiff person syndrome and myasthenia gravis. Neurol India. 2002 Mar. 50(1):98-100. [QxMD MEDLINE Link].
Shariatmadar S, Noto TA. Plasma exchange in stiff-man syndrome. Ther Apher. 2001 Feb. 5(1):64-7. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].

Media Gallery

of 0

Author

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 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.

Sections Stiff Person Syndrome
Overview
Presentation
- History
- Physical
- Causes
- Show All
DDx
Workup
Treatment
Medication
Follow-up
Questions & Answers
References

Stiff Person Syndrome Treatment & Management

Medical Care

Consultations

Activity

References

Tables

Contributor Information and Disclosures

What would you like to print?