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Stiff-Man Syndrome: Pathogenetic, Nosological and Therapeutic Considerations

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Autoantibodies in Neurological Diseases

Part of the book series: Topics in Neuroscience ((TOPNEURO))

Abstract

The acronym SMS (Stiff-Man Syndrome) identifies a syndrome of slowly progressive stiffness involving skeletal muscles (mainly axial) with superimposed muscle spasms. It was first described by Moersch and Woltmann in 1956 [1]. A set of diagnostic criteria was proposed by Gordon et al. [2] and Lorish et al. [3]. Diagnostic criteria included: 1) a prodrome of stiffness and rigidity in axial muscles; 2) a slow progression of stiffness involving proximal limb muscles, making walking difficult; 3) a fixed deformity, usually lordosis, of the spine; 4) the presence of superimposed muscle spasms, often precipitated by external stimuli; 5) normal motor and sensory nerve findings; 6) normal mental status and 7) an EMG finding of continuous motor unit activity (CMUA) at rest, abolished by intravenous diazepam or reduced by orally administered diazepam. It has been recently debated whether SMS is a single disease entity. Thirty-eight reported SMS patients were rexamined [4]; only seven of them (18.4%) fulfilled the Lorish diagnostic criteria [3].

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References

  1. Moersch FP, Woltmann HW (1956) Progressive fluctuating muscular rigidity and spasm (stiff-man syndrome): report of a case and some observations in 13 other cases. Mayo Clin Proc 31:421–427

    CAS  Google Scholar 

  2. Gordon EE, Januszko DM, Kaufman L (1967) A critical survey of stiff-man syndrome. Am J Med 42:582–599

    Article  PubMed  CAS  Google Scholar 

  3. Lorish TR, Thorsteinsson G, Howard FM (1989) Stiff-man syndrome updated. Mayo Clin Proc 64: 629–636

    PubMed  CAS  Google Scholar 

  4. Piccolo G, Moglia A (1993) Stiff-man syndrome: one disease entity or more. In: Layzer RB, Sandrini G, Piccolo G, Martinelli M (eds) Motor Unit Hyperactivity States, Raven Press New York pp 23–30)

    Google Scholar 

  5. Brown P, Marsden CD (1999) The stiff man and stiff man plus syndrome. J Neurol 246:648–652

    Article  PubMed  CAS  Google Scholar 

  6. Howard FM Jr (1963) A new and effective drug in the treatment of stiff-man syndrome: preliminary report. Mayo Clin Proc 38:203–212

    Google Scholar 

  7. Cohen L (1966) Stiff-man syndrome: two patients treated with diazepam. JAMA 195:222–224

    Article  PubMed  CAS  Google Scholar 

  8. Westblom U (1977) Stiff-man syndrome and clonazepam. JAMA 237:1930

    Article  PubMed  CAS  Google Scholar 

  9. Spehlmann R, Norcross K, Rasmus SC, Schlageter NL (1981) Improvement of stiff-man syndrome with sodium valproate. Neurology 31:162–163

    Article  Google Scholar 

  10. Meinck H-M, Conrad B (1986) Neuropharmacological investigations in the stiff-man syndrome. J Neurol 233:340–347

    Article  PubMed  CAS  Google Scholar 

  11. Boiardi A, Crenna P, Bussone G et al (1980) Neurological and pharmacological evaluation of a case of stiff-man syndrome. J Neurol 223:127–33

    Article  PubMed  CAS  Google Scholar 

  12. Henningsen P, Clement U, Kuchenhoff J et al (1996) Psychological factors in the diagnosis and pathogenesis of stiff-man syndrome. Neurology 47:38–42

    Article  PubMed  CAS  Google Scholar 

  13. Black JL, Barth EM, Williams DE, Tinsley JA (1998) Stiff-man syndrome. Results of interviews and psychologic testing. Psychosomatics 39:38–44

    Article  PubMed  CAS  Google Scholar 

  14. Tinsley JA, Barth EM, Black JL, Williams DE (1997) Psychiatric consuhations in stiffman syndrome. J Clin Psychiatry 58:444–449

    Article  PubMed  CAS  Google Scholar 

  15. Mitsumoto H, Schwartzman MJ, Estes ML et al (1991) Sudden death and paroxysmal autonomic dysfunction in stiff-man syndrome. J. Neurol 238:91–96

    Article  PubMed  CAS  Google Scholar 

  16. Floeter MK, Valls-Solè J, Toro C et al (1998) Physiologic studies of spinal inhibitory circuits in patients with stiff-person syndrome. Neurology 51:85–93

    Article  PubMed  CAS  Google Scholar 

  17. Levy LM, Dalakas MC, Floeter MK (1999) The stiff-person syndrome: an autoimmune disorder affecting neurotransmission of gamma-aminobutyric acid. Ann Intern Med 13:522–530

    Google Scholar 

  18. Solimena M, Folli F, Denis-Donini S et al (1988) Autoantibodies to glutamic acid decarboxilase in a patient with stiff-man syndrome, epilepsy, and type I diabetes mellitus. N Engl J Med 318:1012–1020

    Article  PubMed  CAS  Google Scholar 

  19. Oertel WH, Schmechel DE, Mugnaini E et al (1981) Immunocytochemical localization of glutamate decarboxylase in rat cerebellum with a new antiserum. Neuroscience 6:2715–2735

    Article  PubMed  CAS  Google Scholar 

  20. Mugnaini E, Oertel WH (1985) An atlas of the distribution of GABAergic neurons and terminals in the rat CNS as revealed by GAD immunohistochemistry. In: Björklund A, Hökfelt T (eds) Handbook of Chemical Neuroanatomy. Vol 4. GABA and neuropeptides in the CNS, Part I. Amsterdam, Elsevier Science Publishers, pp 436–608

    Google Scholar 

  21. Palay SL, Chan-Palay V (1974) Cerebellar cortex: cytology and organization. Springer-Verlag, New York

    Book  Google Scholar 

  22. Kaufman DL, McGinnis JF, Krieger NR, Tobin AJ (1986) Brain glutamate decarboxilase-cloned in labda yt-U: fusion protein produces gamma-aminobutyric acid. Science 232:1138–1140

    Article  PubMed  CAS  Google Scholar 

  23. Erlander MG, Tillakatne NJK, Feldblum S et al (1991) Two genes encode distinct glutamate decarboxilases. Neuron 7:91–100

    Article  PubMed  CAS  Google Scholar 

  24. Pugliese A, Gianani R, Eisenbarth GS et al (1994) Genetics of susceptibility and resistance to insulin-dependent diabetes in stiff-man syndrome. Lancet 344:1027–8

    Article  PubMed  CAS  Google Scholar 

  25. Williams AC, Nutt JG, Hare T (1988) Autoimmunity in stiff-man syndrome. Lancet 2:222

    Article  PubMed  CAS  Google Scholar 

  26. Reetz A, Solimena M, Matteoli M et al (1991) G ABA and pancreatic ß-cells: colocalization of glutamic acid decarboxilase (GAD) and G AB A with synaptic-like microvescicles suggests their role in GABA storage and secretion. EMBO J 10:1275–1284

    PubMed  CAS  Google Scholar 

  27. Vincent SR, Hokfelt T, Wu J-Y et al (1983) Immunohistochemical studies of the GABA system in the pancreas. Neuroendocrinology 36:197–204

    Article  PubMed  CAS  Google Scholar 

  28. Persson H, Pelto-Huikko M, Metsis M et al (1990) Expression of the neurotransmittersynthesizing enzyme glutamic acid decarboxilase in male germ cells. Mol Cell Biol 10:4701–4711

    PubMed  CAS  Google Scholar 

  29. Erdo SL, Joo F, Wolff JR (1989) Immunohistochemical localization of glutamate decarboxilase in the rat oviduct and ovary: further evidence for non-neural GABA systems. Cell Tissue Res 255:431–434

    Article  PubMed  CAS  Google Scholar 

  30. Solimena M, Folli F, Aparisi R et al (1990) Autoantibodies to GABA-ergic neurons and pancreatic beta cells in stiff-man syndrome. N Engl I Med (1990) 322:1555–1560

    Article  CAS  Google Scholar 

  31. Grimaldi LME, Martino G, Braghi S et al (1993) Heterogeneity of autoantibodies in stiff-man syndrome. Ann Neurol 34:57–64

    Article  PubMed  CAS  Google Scholar 

  32. McEvoy KM (1991) Stiff-man syndrome. Seminars in Neurology 11:197–205

    Article  PubMed  CAS  Google Scholar 

  33. Toro C, Jacobowitz DM, Hallett M (1994) Stiff-man syndrome. Seminars in Neurology 14:154–158

    Article  PubMed  CAS  Google Scholar 

  34. Gorin F, Baldwin B, Tait R et al (1990) Stiff-man syndrome: a GABAergic autoimmune disorder with autoantigenic heterogeneity. Ann Neurol 28:71–74

    Article  Google Scholar 

  35. Harding AE, Thompson PD, Kocen RS et al (1989) Plasma exchange and immunosup-pression in the stiff man syndrome. Lancet 2:915

    Article  PubMed  CAS  Google Scholar 

  36. Baekkeskov S, Aanstoot H-J, Christgau S et al (1990) Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxilase. Nature 347:151–156

    Article  PubMed  CAS  Google Scholar 

  37. Lernmark A (1996) Glutamic acid decarboxylase-gene to antigen to disease. J Intern Med 240:259–277

    Article  PubMed  CAS  Google Scholar 

  38. Saiz A, Arpa J, Sagasta A et al (1997) Autoantibodies to glutamic acid decarboxilase in three patients with cerebellar ataxia, late-onset insulin dependent diabetes mellitus, and polyendocrine autoimmunity. Neurology 49:1026–1030

    Article  PubMed  CAS  Google Scholar 

  39. Nemni R, Braghi S, Natali-Sora MG et al (1994) Autoantibodies to glutamic acid decar-boxylase in palatal myoclonus and epilepsy. Ann Neurol 36:665–7

    Article  PubMed  CAS  Google Scholar 

  40. Folli F, Solimena M, Cofiell R et al (1993) Autoantibodies to a 128-kd protein in three women with the stiff-man syndrome and breast cancer. N Engl J Med 328:546–551

    Article  PubMed  CAS  Google Scholar 

  41. Masson C, Prier S, Benoit C et al (1987) Amnésie, syndrome de V homme raide: Manifestations révélatrices d’une encéphalomyélite paranéoplastique. Ann Med Interne 138:502–505

    CAS  Google Scholar 

  42. Piccolo G, Cosi V, Zandrini C, Moglia A (1988) Steroid-responsive and dependent stiffman syndrome: a clinical and electrophysiological study of two cases. Ital J Neurol Sei 9:559–566

    Article  CAS  Google Scholar 

  43. Piccolo G, Cosi V (1989) Stiff man syndrome, dysimmune disorder, and cancer. Ann Neurol 26:105

    Article  PubMed  CAS  Google Scholar 

  44. Bateman DE, Weller RO, Kennedy P (1990) Stiff man syndrome: a rare paraneoplastic disorder? J Neurol Neurosurg Psichiatry 53:695–696

    Article  CAS  Google Scholar 

  45. Silverman IE (1999) Paraneoplastic stiff limb syndrome. J Neurol Neurosurg Psychiatry 67:126–7

    Article  PubMed  CAS  Google Scholar 

  46. Valldeoriola F (1999) Movement disorders of autoimmune origin. J Neurol 246:423–431

    Article  PubMed  CAS  Google Scholar 

  47. De CamilH P, Cameron R, Greengard P (1983) Synapsin I (protein I), a nerve terminal-specific phosphoprotein. I. Its general distribution in synapses of the central and peripheral nervous system demonstrated by immunofluorescence in frozen and plastic sections, J Cell Biol 96:1337–1354

    Article  Google Scholar 

  48. Navone F, Jahn R, Di Gioia G et al (1986) Protein p38: an integral membrane protein specific for small vescicles of neurons and neuroendocrine cells. J Cell Biol 103:2511–2527

    Article  PubMed  CAS  Google Scholar 

  49. De CamilH P, Thomas A, Cofiell R et al (1993) The synaptic vesicle-associated protein amphiphysin is the 128-kD autoantigen of Stiff-Man Syndrome with breast cancer. J Exp Med 178:2219–2223

    Article  Google Scholar 

  50. Dropcho EJ (1996) Antiamphiphysin antibodies with small-cell lung carcinoma and paraneoplastic encephalomyelitis. Ann Neurol 43:659–667

    Article  Google Scholar 

  51. Saiz A, Dalmau J, Butler MH et al (1999) Anti-amphiphysin I antibodies in patients with paraneoplastic neurological disorders associated with small cell lung carcinoma. J Neurol Neurosurg Psychiatry 66:214–7

    Article  PubMed  CAS  Google Scholar 

  52. Antoine JC, Absi L, Honnorat J et al (1999) Antiamphiphysin antibodies are associated with various paraneoplastic neurological syndromes and tumors. Arch Neurol 56:172–7

    Article  PubMed  CAS  Google Scholar 

  53. Martino G, Grimaldi LM, Bazzigaluppi E et al (1996) The insuHn-dependent diabetes mellitus-associated ICA 105 autoantigen in stiff-man syndrome patients. J Neuro-immunol 69:129–134

    CAS  Google Scholar 

  54. Morgenthaler NG, Geissler J, Achenbach P et al (1997) Antibodies to the tyrosine phosphatase-like protein IA-2 are highly associated with IDDM, but not with autoimmune endocrine diseases or stiff man syndrome. Autoimmunity 25:203–211

    Article  PubMed  CAS  Google Scholar 

  55. Warich-Kirches M, Von Bossanyi P, Treuheit T et al (1997) Stiff-man syndrome: possible autoimmune etiology targeted against GABA-ergic cells. Clinical Neuropathology 16:214–219

    PubMed  CAS  Google Scholar 

  56. Whiteley AM, Swash M, Urich H (1976) Progressive encephalomyelitis with rigidity. Its relation to “subacute myoclonic spinal neuronitis” and to the “stiff-man syndrome.” Brain 99:27–42

    Article  PubMed  CAS  Google Scholar 

  57. Leigh PN, Rothwell JC, Traub M, Marsden CD (1980) A patient with reflex myoclonus and muscle rigidity: jerking stiff-man syndrome. J. Neurol Neurosurg Psichiatry 43:1125–1131

    Article  CAS  Google Scholar 

  58. Barker RA, Revesz T, Thom M et al (1998) Review of 23 patients affected by stiff-man syndrome: clinical subdivision into stiff trunk (man) syndrome, stiff-limb syndrome, and progressive encephalomyelitis with rigidity. J Neurol Neurosurg Psychiatry 65:633–640

    Article  PubMed  CAS  Google Scholar 

  59. Folli F (1998) Stiff man syndrome, 40 years later. J Neurol Neurosurg Psychiatry 65:618

    Article  PubMed  CAS  Google Scholar 

  60. Saiz A, Graus F, Valldeoriola F et al (1998) Stiff-leg syndrome: a focal form of stiff-man syndrome. Ann Neurol 43:400–401

    Article  PubMed  CAS  Google Scholar 

  61. Shaw PJ (1999) Stiff-man syndrome and its variants. Lancet 353:86–87

    CAS  Google Scholar 

  62. Liguori R, Medori R, Marcello L et al (1993) Vigabatrin improves rigidity in stiff-person syndrome (SPS). Neurology 43:311

    Google Scholar 

  63. IA Sharoqi (1998) Improvement of stiff-man syndrome with vigabatrin. Neurology 50:833–834

    Article  PubMed  CAS  Google Scholar 

  64. Stayer C, Tronnier V, Dressnandt J et al (1997) Intrathecal baclofen therapy for stiffman syndrome and progressive encephalomyelopathy with rigidity and myoclonus. Neurology 49:1591–1597

    Article  PubMed  CAS  Google Scholar 

  65. Liguori L, Cordivari C, Lugaresi E, Montagna P (1997) Botulinum Toxin A improves muscle spasms and rigidity in Stiff-person syndrome. Movement Disorders 12:1060–1063

    Article  PubMed  CAS  Google Scholar 

  66. Shmierer K, Valduzca IM, Bender A et al (1998) Atypical stiff-person syndrome with spinal MRI findings, amphiphysin autoantibodies, and immunosuppression. Neurology 51:250–252

    Article  Google Scholar 

  67. McCombe PA, Chalk JB, Searle IW et al (1989) Progressive encephalomyelitis with rigidity: a case report with magnetic resonance imaging findings. I Neurol Neurosurg Psychiatry 52:1429–1431

    Article  CAS  Google Scholar 

  68. Barker RA, Marsden CD (1997) Successful treatment of stiff-man syndrome with intravenous immunoglobulin. J Neurol Neurosurg Psychiatry 62:426–7

    Article  PubMed  CAS  Google Scholar 

  69. Amato AA, Cornman EW, Kissel JT (1994) Treatment of stiff-man syndrome with intravenous immunoglobulin. Neurology 44:1652–1660

    Article  PubMed  CAS  Google Scholar 

  70. Vicari AM, Folli F, Pozza G et al (1989) Plasmapheresis in the treatment of Stiff-Man Syndrome. N Engl] Med 320:1499

    CAS  Google Scholar 

  71. Hummel M, Durinovic-Bello I, Bonifacio E et al (1998) Humoral and cellular immune parameters before and after immunosuppressive therapy of a patient with stiff-man syndrome and insulin dependent diabetes mellitus. I Neurol Neurosurgery and Psychiatry 65:204–208

    Article  CAS  Google Scholar 

  72. Hao W, Davis C, Hirsch IB et al (1999) Plasmapheresis and immunosuppression in stiff-man syndrome with type 1 diabetes: a 2-year study. J Neurol 246:731–735

    Article  PubMed  CAS  Google Scholar 

  73. Brashear HR, Phillips LH (1991) Autoantibodies to GABAergic neurons and response to plasmapheresis in stiff-man syndrome. Neurology 41:1588–1592

    Article  PubMed  CAS  Google Scholar 

  74. Anonimous (1996) Assessment of plasmapheresis. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 47:840–843

    Article  Google Scholar 

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Authors and Affiliations

  1. Unit for Metabolic Diseases and Department of Medicine, San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy

    F. Folli

  2. Department of Neurology, Fondazione Mondino, University of Pavia, Italy

    G. Piccolo

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  1. F. Folli
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  2. G. Piccolo
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Editors and Affiliations

  1. Neurosciences Group, Department of Clinical Neurology, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK

    Angela Vincent

  2. Neuroimmunology Unit, Department of Neuroscience, San Raffaele Scientific Institute, Milan, Italy

    Gianvito Martino

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Folli, F., Piccolo, G. (2002). Stiff-Man Syndrome: Pathogenetic, Nosological and Therapeutic Considerations. In: Vincent, A., Martino, G. (eds) Autoantibodies in Neurological Diseases. Topics in Neuroscience. Springer, Milano. https://doi.org/10.1007/978-88-470-2097-9_10

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  • DOI: https://doi.org/10.1007/978-88-470-2097-9_10

  • Publisher Name: Springer, Milano

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