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Treatment of Stiff-Person Spectrum Disorders

  • Pichet Termsarasab
  • Thananan Thammongkolchai
  • Bashar Katirji
Chapter
  • 111 Downloads

Abstract

Treatment of stiff-person spectrum disorders is usually divided into symptomatic and specific therapies. Symptomatic therapies include benzodiazepines, baclofen, tizanidine, and, less commonly, antiepileptic medications. The most commonly used medication for symptomatic treatment is diazepam. Given autoimmunity as a main pathophysiological basis, specific immunotherapies therapies include corticosteroids, corticosteroid-sparing agents, intravenous immunoglobulin, plasma exchange, and rituximab. Data from clinical trials to suggest treatment selection in clinical practice remain lacking, given the rarity of SPSD. Multiple different approaches are based on clinical experience. The targeted approach with stratification of patients by severity and clinical phenotypes is recommended. In patients with severe symptoms or aggressive phenotypes such as progressive encephalomyelitis with rigidity and myoclonus, immunotherapies should be considered early.

Keywords

Stiff-person syndrome Treatment Benzodiazepines Baclofen Tizanidine Immunotherapies Intravenous immunoglobulin Plasma exchange Corticosteroids Rituximab 

References

  1. 1.
    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
  2. 2.
    Siegel GJ, Agranoff BW. Basic neurochemistry: molecular, cellular, and medical aspects. 6th ed ed. Philadelphia: Lippincott-Raven Publishers; 1999.Google Scholar
  3. 3.
    Greenblatt DJ, Shader RI, Divoll M, Harmatz JS. Benzodiazepines: a summary of pharmacokinetic properties. Br J Clin Pharmacol. 1981;11(Suppl 1):11S–6S.  https://doi.org/10.1111/j.1365-2125.1981.tb01833.x.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Griffin CE 3rd, Kaye AM, Bueno FR, Kaye AD. Benzodiazepine pharmacology and central nervous system-mediated effects. Ochsner J. 2013;13(2):214–23.PubMedPubMedCentralGoogle Scholar
  5. 5.
    McIntosh B, Clark M, Spry C. Benzodiazepines in older adults: a review of clinical effectiveness, cost-effectiveness, and guidelines. CADTH Rapid Response Reports. Ottawa; 2011.Google Scholar
  6. 6.
    Westblom U. Stiff-man syndrome and clonazepam. JAMA. 1977;237(18):1930.CrossRefGoogle Scholar
  7. 7.
    Vasconcelos OM, Dalakas MC. Stiff-person Syndrome. Curr Treat Options Neurol. 2003;5(1):79–90.  https://doi.org/10.1007/s11940-003-0024-x.CrossRefPubMedGoogle Scholar
  8. 8.
    Gordon EE, Januszko DM, Kaufman L. A critical survey of stiff-man syndrome. Am J Med. 1967;42(4):582–99.  https://doi.org/10.1016/0002-9343(67)90057-5.CrossRefPubMedGoogle Scholar
  9. 9.
    Lorish TR, Thorsteinsson G, Howard FM Jr. Stiff-man syndrome updated. Mayo Clin Proc. 1989;64(6):629–36.  https://doi.org/10.1016/s0025-6196(12)65339-7.CrossRefPubMedGoogle Scholar
  10. 10.
    Folli F, Prioletta A, Quattrini A, Galardi G. Stiff-man syndrome. In: Katirji B, Kaminski HJ, Ruff RL, editors. Neuromuscular disorders in clinical practice. Second ed. New York: Sprinker; 2014. p. 1465–77.CrossRefGoogle Scholar
  11. 11.
    Whelan JL. Baclofen in treatment of the ‘stiff-man’ syndrome. Arch Neurol. 1980;37(9):600–1.  https://doi.org/10.1001/archneur.1980.00500580096024.CrossRefPubMedGoogle Scholar
  12. 12.
    Miller F, Korsvik H. Baclofen in the treatment of stiff-man syndrome. Ann Neurol. 1981;9(5):511–2.  https://doi.org/10.1002/ana.410090516.CrossRefPubMedGoogle Scholar
  13. 13.
    Penn RD, Mangieri EA. Stiff-man syndrome treated with intrathecal baclofen. Neurology. 1993;43(11):2412.  https://doi.org/10.1212/wnl.43.11.2412.CrossRefPubMedGoogle Scholar
  14. 14.
    Seitz RJ, Blank B, Kiwit JC, Benecke R. Stiff-person syndrome with anti-glutamic acid decarboxylase autoantibodies: complete remission of symptoms after intrathecal baclofen administration. J Neurol. 1995;242(10):618–22.  https://doi.org/10.1007/bf00866910.CrossRefPubMedGoogle Scholar
  15. 15.
    Silbert PL, Matsumoto JY, McManis PG, Stolp-Smith KA, Elliott BA, McEvoy KM. Intrathecal baclofen therapy in stiff-man syndrome: a double-blind, placebo-controlled trial. Neurology. 1995;45(10):1893–7.  https://doi.org/10.1212/wnl.45.10.1893.CrossRefPubMedGoogle Scholar
  16. 16.
    Stayer C, Tronnier V, Dressnandt J, Mauch E, Marquardt G, Rieke K, et al. Intrathecal baclofen therapy for stiff-man syndrome and progressive encephalomyelopathy with rigidity and myoclonus. Neurology. 1997;49(6):1591–7.  https://doi.org/10.1212/wnl.49.6.1591.CrossRefPubMedGoogle Scholar
  17. 17.
    Meinck HM, Tronnier V, Rieke K, Wirtz CR, Flugel D, Schwab S. Intrathecal baclofen treatment for stiff-man syndrome: pump failure may be fatal. Neurology. 1994;44(11):2209–10.  https://doi.org/10.1212/wnl.44.11.2209.CrossRefPubMedGoogle Scholar
  18. 18.
    Bardutzky J, Tronnier V, Schwab S, Meinck HM. Intrathecal baclofen for stiff-person syndrome: life-threatening intermittent catheter leakage. Neurology. 2003;60(12):1976–8.  https://doi.org/10.1212/wnl.60.12.1976.CrossRefPubMedGoogle Scholar
  19. 19.
    Ghanavatian S, Derian A. Tizanidine. Treasure Island: StatPearls; 2019.Google Scholar
  20. 20.
    Milanov I, Georgiev D. Mechanisms of tizanidine action on spasticity. Acta Neurol Scand. 1994;89(4):274–9.  https://doi.org/10.1111/j.1600-0404.1994.tb01680.x.CrossRefPubMedGoogle Scholar
  21. 21.
    Meinck HM, Ricker K, Conrad B. The stiff-man syndrome: new pathophysiological aspects from abnormal exteroceptive reflexes and the response to clomipramine, clonidine, and tizanidine. J Neurol Neurosurg Psychiatry. 1984;47(3):280–7.  https://doi.org/10.1136/jnnp.47.3.280.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Zdziarski P. A case of stiff person syndrome: immunomodulatory effect of benzodiazepines: successful rituximab and tizanidine therapy. Medicine (Baltimore). 2015;94(23):e954.  https://doi.org/10.1097/MD.0000000000000954.CrossRefGoogle Scholar
  23. 23.
    Spehlmann R, Norcross K, Rasmus SC, Schlageter NL. Improvement of stiff-man syndrome with sodium valproate. Neurology. 1981;31(9):1162–3.  https://doi.org/10.1212/wnl.31.9.1162.CrossRefPubMedGoogle Scholar
  24. 24.
    Vermeij FH, van Doorn PA, Busch HF. Improvement of stiff-man syndrome with vigabatrin. Lancet. 1996;348(9027):612.  https://doi.org/10.1016/S0140-6736(05)64825-8.CrossRefPubMedGoogle Scholar
  25. 25.
    Prevett MC, Brown P, Duncan JS. Improvement of stiff-man syndrome with vigabatrin. Neurology. 1997;48(4):1133–4.  https://doi.org/10.1212/wnl.48.4.1133-a.CrossRefPubMedGoogle Scholar
  26. 26.
    Murinson BB, Rizzo M. Improvement of stiff-person syndrome with tiagabine. Neurology. 2001;57(2):366.  https://doi.org/10.1212/wnl.57.2.366.CrossRefPubMedGoogle Scholar
  27. 27.
    Ruegg SJ, Steck AJ, Fuhr P. Levetiracetam improves paroxysmal symptoms in a patient with stiff-person syndrome. Neurology. 2004;62(2):338.  https://doi.org/10.1212/01.wnl.0000103442.27580.5b.CrossRefPubMedGoogle Scholar
  28. 28.
    Sechi G, Barrocu M, Piluzza MG, Cocco GA, Deiana GA, Sau GF. Levetiracetam in stiff-person syndrome. J Neurol. 2008;255(11):1721–5.  https://doi.org/10.1007/s00415-008-0007-7.CrossRefPubMedGoogle Scholar
  29. 29.
    Voci JM, al-Hakim M, Dokko Y, Katirji MB. Intravenous methocarbamol in the treatment of stiff-man syndrome. Muscle Nerve. 1993;16(4):434–5.PubMedGoogle Scholar
  30. 30.
    Davis D, Jabbari B. Significant improvement of stiff-person syndrome after paraspinal injection of botulinum toxin A. Mov Disord. 1993;8(3):371–3.  https://doi.org/10.1002/mds.870080323.CrossRefPubMedGoogle Scholar
  31. 31.
    Liguori R, Cordivari C, Lugaresi E, Montagna P. Botulinum toxin A improves muscle spasms and rigidity in stiff-person syndrome. Mov Disord. 1997;12(6):1060–3.  https://doi.org/10.1002/mds.870120636.CrossRefPubMedGoogle Scholar
  32. 32.
    Conners LM, Betcher A, Shahinian A, Janda P. Utility of botulinum injections in stiff-person syndrome. Case Rep Neurol Med. 2019;2019:9317916.  https://doi.org/10.1155/2019/9317916.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Barnes PJ. How corticosteroids control inflammation: quintiles prize lecture 2005. Br J Pharmacol. 2006;148(3):245–54.  https://doi.org/10.1038/sj.bjp.0706736.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Ramamoorthy S, Cidlowski JA. Corticosteroids: mechanisms of action in health and disease. Rheum Dis Clin N Am. 2016;42(1):15–31., vii.  https://doi.org/10.1016/j.rdc.2015.08.002.CrossRefGoogle Scholar
  35. 35.
    Piccolo G, Cosi V, Zandrini C, Moglia A. Steroid-responsive and dependent stiff-man syndrome: a clinical and electrophysiological study of two cases. Ital J Neurol Sci. 1988;9(6):559–66.  https://doi.org/10.1007/bf02337009.CrossRefPubMedGoogle Scholar
  36. 36.
    Daif A, Lukas RV, Issa NP, Javed A, VanHaerents S, Reder AT, et al. Antiglutamic acid decarboxylase 65 (GAD65) antibody-associated epilepsy. Epilepsy Behav. 2018;80:331–6.  https://doi.org/10.1016/j.yebeh.2018.01.021.CrossRefPubMedGoogle Scholar
  37. 37.
    Hartung HP. Advances in the understanding of the mechanism of action of IVIG. J Neurol. 2008;255(Suppl 3):3–6.  https://doi.org/10.1007/s00415-008-3002-0.CrossRefPubMedGoogle Scholar
  38. 38.
    Ahmed AR, Kaveri S. Reversing autoimmunity combination of rituximab and intravenous immunoglobulin. Front Immunol. 2018;9:1189.  https://doi.org/10.3389/fimmu.2018.01189.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Galeotti C, Kaveri SV, Bayry J. IVIG-mediated effector functions in autoimmune and inflammatory diseases. Int Immunol. 2017;29(11):491–8.  https://doi.org/10.1093/intimm/dxx039.CrossRefPubMedGoogle Scholar
  40. 40.
    Amato AA, Cornman EW, Kissel JT. Treatment of stiff-man syndrome with intravenous immunoglobulin. Neurology. 1994;44(9):1652–4.  https://doi.org/10.1212/wnl.44.9.1652.CrossRefPubMedGoogle Scholar
  41. 41.
    Dalakas MC, Fujii M, Li M, Lutfi B, Kyhos J, McElroy B. High-dose intravenous immune globulin for stiff-person syndrome. N Engl J Med. 2001;345(26):1870–6.  https://doi.org/10.1056/NEJMoa01167.CrossRefPubMedGoogle Scholar
  42. 42.
    Stern WM, Howard R, Chalmers RM, Woodhall MR, Waters P, Vincent A, et al. Glycine receptor antibody mediated Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM): a rare but treatable neurological syndrome. Pract Neurol. 2014;14(2):123–7.  https://doi.org/10.1136/practneurol-2013-000511.CrossRefPubMedGoogle Scholar
  43. 43.
    Molina JA, Porta J, Garcia-Morales I, Bermejo PF, Jimenez-Jimenez FJ. Treatment with intravenous prednisone and immunoglobin in a case of progressive encephalomyelitis with rigidity. J Neurol Neurosurg Psychiatry. 2000;68(3):395–6.  https://doi.org/10.1136/jnnp.68.3.395a.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Uehara T, Murai H, Yamasaki R, Kikuchi H, Shigeto H, Ohyagi Y, et al. Thymoma-associated progressive encephalomyelitis with rigidity and myoclonus successfully treated with thymectomy and intravenous immunoglobulin. Eur Neurol. 2011;66(6):328–30.  https://doi.org/10.1159/000332033.CrossRefPubMedGoogle Scholar
  45. 45.
    Dalmau J, Geis C, Graus F. Autoantibodies to synaptic receptors and neuronal cell surface proteins in autoimmune diseases of the central nervous system. Physiol Rev. 2017;97(2):839–87.  https://doi.org/10.1152/physrev.00010.2016.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Quek AM, Britton JW, McKeon A, So E, Lennon VA, Shin C, et al. Autoimmune epilepsy: clinical characteristics and response to immunotherapy. Arch Neurol. 2012;69(5):582–93.  https://doi.org/10.1001/archneurol.2011.2985.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Lauria G, Pareyson D, Pitzolu MG, Bazzigaluppi E. Excellent response to steroid treatment in anti-GAD cerebellar ataxia. Lancet Neurol. 2003;2(10):634–5.  https://doi.org/10.1016/s1474-4422(03)00534-9.CrossRefPubMedGoogle Scholar
  48. 48.
    Bonnan M, Cabre P, Olindo S, Signate A, Saint-Vil M, Smadja D. Steroid treatment in four cases of anti-GAD cerebellar ataxia. Rev Neurol (Paris). 2008;164(5):427–33.  https://doi.org/10.1016/j.neurol.2008.02.032.CrossRefGoogle Scholar
  49. 49.
    Vicari AM, Folli F, Pozza G, Comi GC, Comola M, Canal N, et al. Plasmapheresis in the treatment of stiff-man syndrome. N Engl J Med. 1989;320(22):1499.PubMedGoogle Scholar
  50. 50.
    Brashear HR, Phillips LH 2nd. Autoantibodies to GABAergic neurons and response to plasmapheresis in stiff-man syndrome. Neurology. 1991;41(10):1588–92.  https://doi.org/10.1212/wnl.41.10.1588.CrossRefPubMedGoogle Scholar
  51. 51.
    Fogan L. Progressive encephalomyelitis with rigidity responsive to plasmapheresis and immunosuppression. Ann Neurol. 1996;40(3):451–3.  https://doi.org/10.1002/ana.410400315.CrossRefPubMedGoogle Scholar
  52. 52.
    Lehmann HC, Hartung HP, Hetzel GR, Stuve O, Kieseier BC. Plasma exchange in neuroimmunological disorders: Part 1: rationale and treatment of inflammatory central nervous system disorders. Arch Neurol. 2006;63(7):930–5.  https://doi.org/10.1001/archneur.63.7.930.CrossRefPubMedGoogle Scholar
  53. 53.
    Cerny T, Borisch B, Introna M, Johnson P, Rose AL. Mechanism of action of rituximab. Anti-Cancer Drugs. 2002;13(Suppl 2):S3–10.  https://doi.org/10.1097/00001813-200211002-00002.CrossRefPubMedGoogle Scholar
  54. 54.
    Randall KL. Rituximab in autoimmune diseases. Aust Prescr. 2016;39(4):131–4.  https://doi.org/10.18773/austprescr.2016.053.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Lobo ME, Araujo ML, Tomaz CA, Allam N. Stiff-person syndrome treated with rituximab. BMJ Case Rep. 2010;2010  https://doi.org/10.1136/bcr.05.2010.3021.Google Scholar
  56. 56.
    Dupond JL, Essalmi L, Gil H, Meaux-Ruault N, Hafsaoui C. Rituximab treatment of stiff-person syndrome in a patient with thymoma, diabetes mellitus and autoimmune thyroiditis. J Clin Neurosci. 2010;17(3):389–91.  https://doi.org/10.1016/j.jocn.2009.06.015.CrossRefPubMedGoogle Scholar
  57. 57.
    Katoh N, Matsuda M, Ishii W, Morita H, Ikeda S. Successful treatment with rituximab in a patient with stiff-person syndrome complicated by dysthyroid ophthalmopathy. Intern Med. 2010;49(3):237–41.  https://doi.org/10.2169/internalmedicine.49.2821.CrossRefPubMedGoogle Scholar
  58. 58.
    Kashif M, Qureshi A, Adil SN, Khurshid M. Successful use of rituximab in Evans syndrome and refractory immune thrombocytopenic purpura. J Pak Med Assoc. 2010;60(1):64–5.PubMedGoogle Scholar
  59. 59.
    Dalakas MC, Rakocevic G, Dambrosia JM, Alexopoulos H, McElroy B. A double-blind, placebo-controlled study of rituximab in patients with stiff person syndrome. Ann Neurol. 2017;82(2):271–7.  https://doi.org/10.1002/ana.25002.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Sengupta S, Tarsy D, Joyce R, Jeyapalan S. Novel use of dual immunomodulation for treating stiff-person syndrome, cerebellar variant. Mov Disord. 2013;28(13):1905–6.  https://doi.org/10.1002/mds.25574.CrossRefPubMedGoogle Scholar
  61. 61.
    Triplett J, Vijayan S, MacDonald A, Lawn N, McLean-Tooke A, Bynevelt M, et al. Fulminant anti-GAD antibody encephalitis presenting with status epilepticus requiring aggressive immunosuppression. J Neuroimmunol. 2018;323:119–24.  https://doi.org/10.1016/j.jneuroim.2018.06.013.CrossRefPubMedGoogle Scholar
  62. 62.
    Termsarasab P, Katirji B. Opportunistic infections in myasthenia gravis treated with mycophenolate mofetil. J Neuroimmunol. 2012;249(1–2):83–5.  https://doi.org/10.1016/j.jneuroim.2012.04.016.CrossRefPubMedGoogle Scholar
  63. 63.
    Termsarasab P, Katirji B. Brainstem lymphoma in a myasthenia gravis patient on azathioprine. J Clin Neurosci. 2015;22(2):415–8.  https://doi.org/10.1016/j.jocn.2014.06.104.CrossRefPubMedGoogle Scholar
  64. 64.
    Maltzman JS, Koretzky GA. Azathioprine: old drug, new actions. J Clin Invest. 2003;111(8):1122–4.  https://doi.org/10.1172/JCI18384.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology. 2000;47(2–3):85–118.  https://doi.org/10.1016/s0162-3109(00)00188-0.CrossRefPubMedGoogle Scholar
  66. 66.
    Sevy A, Franques J, Chiche L, Pouget J, Attarian S. Successful treatment with rituximab in a refractory stiff-person syndrome. Rev Neurol (Paris). 2012;168(4):375–8.  https://doi.org/10.1016/j.neurol.2011.09.008.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Pichet Termsarasab
    • 1
  • Thananan Thammongkolchai
    • 1
  • Bashar Katirji
    • 2
  1. 1.Division of NeurologyFaculty of Medicine Ramathibodi Hospital, Mahidol UniversityBangkokThailand
  2. 2.Department of NeurologyUniversity Hospitals Cleveland Medical Center, Case Western Reserve UniversityClevelandUSA

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