Journal of Neurology

, Volume 238, Issue 2, pp 91–96 | Cite as

Sudden death and paroxysmal autonomic dysfunction in stiff-man syndrome

  • Hiroshi Mitsumoto
  • Michael J. Schwartzman
  • Melinda L. Estes
  • Samuel M. Chou
  • Eugene F. La Franchise
  • Pietro De Camilli
  • Michele Solimena
Original Communications


Two women with typical stiff-man syndrome (SMS) developed increasingly frequent attacks of muscle spasms with severe paroxysmal autonomic dysfunctions such as transient hyperpyrexia, diaphoresis, tachypnea, tachycardia, pupillary dilation, and arterial hypertension. Autoantibodies to GABA-ergic neurons were identified in the serum of both patients and in the cerebrospinal fluid of one. Both died suddenly and unexpectedly. General autopsy did not reveal the cause of death. Neuropathological studies revealed perivascular gliosis in the spinal cord and brain stem of one patient and lymphocytic perivascular infiltration in the spinal cord, brain stem, and basal ganglia of the other. The occurrence of a chronic inflammatory reaction in one of the two patients supports the idea that an autoimmune disease against GABA-ergic neurons may be involved in SMS. A review of the literature indicates that functional impairment in SMS is severe and prognosis is unpredictable because of the potential for sudden and unexpected death. Both muscular abnormalities and autonomic dysfunctions may result from autoimmunity directed against GABA-ergic neurons.

Key words

Stiff-man syndrome Autoimmune disease γ-Aminobutyric acid Autonomic dysfunction Sudden death 


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  1. 1.
    Asher R (1958) A woman with stiff-man syndrome. Br Med J I:265–266Google Scholar
  2. 2.
    Campbell AMG, Garland H (1956) Subacute myoclonic spinal neuronitis. J Neurol Neurosurg Psychiatry 19:268–274Google Scholar
  3. 3.
    Cohen L (1966) Stiff-man syndrome: two patients treated with diazepam. JAMA 195:222–224Google Scholar
  4. 4.
    Drake ME Jr (1983) Stiff-man syndrome and dementia. Am J Med 74:1085–1087Google Scholar
  5. 5.
    Finckle BS, McCloskey KL, Goodman LS (1979) Diazepam and drug-associated deaths: a survey in the United States and Canada. JAMA 242:429–434Google Scholar
  6. 6.
    Folli F, Solimena M, Aparisi S, Rozza G, De Camilli P (1989) Stiff-man syndrome and type I diabetes mellitus: additional evidence suggesting a related autoimmune pathogenesis. Diabetologia 32:488Google Scholar
  7. 7.
    George TM, Burke JM, Sobotka PA, Greenberg HS, Vinik AI (1984) Resolution of stiff-man syndrome with cortisol replacement in a patient with deficiencies of ACTH, growth hormone and prolactin. N Engl J Med 310:1511–1513Google Scholar
  8. 8.
    Goetz CG, Klawans HL (1983) On the mechanism of sudden death in Moersch-Woltman syndrome. Neurology 33:930–932Google Scholar
  9. 9.
    Gordon EE, Januszko DM, Kaufman L (1967) A critical survey of stiff-man syndrome. Am J Med 42:582–599Google Scholar
  10. 10.
    Guilleminault J, Sigwald J, Castaigne E (1973) Sleep studies and therapeutic trial with L-dopa in a case of stiff-man syndrome. Eur Neurol 10:89–96Google Scholar
  11. 11.
    Howard FM Jr (1963) A new and effective drug in the treatment of stiff-man syndrome: preliminary report. Mayo Clin Proc 38:203–212Google Scholar
  12. 12.
    Howell DA, Lees AJ, Toghill PJ (1979) Spinal internuncial neurones in progressive encephalomyelitis with rigidity. J Neurol Neurosurg Psychiatry 42:773–785Google Scholar
  13. 13.
    Jay GW, Leestma JE (1981) Sudden death in epilepsy. Acta Neurol Scand 63 [Suppl 82]:1–66Google Scholar
  14. 14.
    Kasperek S, Zebrowski S (1971) Stiff-man syndrome and encephalomyelitis: report of a case. Arch Neurol 24:22–30Google Scholar
  15. 15.
    Laskey W, Polosa C (1988) Characteristics of the sympathetic pre-ganglionic neurons and its synaptic input. Proc Neurobiol 31:47–84Google Scholar
  16. 16.
    Lathers CM, Schraeder PL (1982) Autonomic dysfunction in epilepsy. Epilepsia 23:633–647Google Scholar
  17. 17.
    Lhermitte F, Chain F, Escourolle R, Chedru F, Guilleminault C, Francoual M (1973) Un nouveas cas de contracture tetaniforme distinct du “stiff man syndrome”. Étude pharmacologique et neuropathologique d'un cas d'encéphalomyelite a predominance medullaire. Rev Neurol (Paris) 128:3–21Google Scholar
  18. 18.
    Lorish TR, Thorsteinsson G, Howard FM Jr (1989) Stiff-man syndrome updated. Mayo Clin Proc 64:629–636Google Scholar
  19. 19.
    Maccario M, Blaugh JR, Mena H (1984) Sudden death in Moersch-Woltman syndrome. Neurology 34:407Google Scholar
  20. 20.
    Maida E, Reisner T, Summer K, Sandor-Eggerth H (1980) Stiff-man syndrome with abnormalities in CSF and computerized tomography findings. Arch Neurol 37:182–183Google Scholar
  21. 21.
    Martinelli P, Pazzaglia P, Montagna P, Coccagna G, Rizzuto N, Simonati S, Lugaresi E (1978) Stiff-man syndrome associated with nocturnal myoclonus and epilepsy. J Neurol Neurosurg Psychiatry 41:458–462Google Scholar
  22. 22.
    Masson C, Prier S, Benoit C, et al (1987) Amnésie, syndrome de l'homme raide. Manifestations révélatrices d'une encéphalomyélite paranéoplasique. Ann Med Interne (Paris) 138:502–505Google Scholar
  23. 23.
    Moersch FP, Woltman WH (1956) Progressive and fluctuating muscular rigidity and spasm (“stiff-man syndrome”): report of a case and some observations in 13 other cases. Mayo Clin Proc 31:421–427Google Scholar
  24. 24.
    Nakamura N, Fujiya S, Yahara O, Fujioka Y, Kawakami Y (1986) Stiff-man syndrome with spinal cord lesion. Clin Neuropathol 5:40–46Google Scholar
  25. 25.
    Norris JW (1983) Effects of cerebrovascular lesions on the heart. Neurol Clin 1:87–101Google Scholar
  26. 26.
    Olafson RA, Mulder DW, Howard FM Jr (1964) “Stiff-man” syndrome: a review of the literature, report of three additional cases and discussion of the pathophysiology and therapy. Mayo Clin Proc 39:131–144Google Scholar
  27. 27.
    Piccolo G, Cosi V (1989) Stiff-man syndrome, dysimmune disorder, and cancer. Ann Neurol 26:105Google Scholar
  28. 28.
    Primhak RA, Spicer RD, Variend S (1986) Sudden death after minor abdominal trauma: an unusual presentation of pheochromocytoma. Br J Med 292:95–96Google Scholar
  29. 29.
    Rae SA, Rose PE, Powell-Jackson P, Goodwill CJ, Fernades L, Berry H, Scott JT (1988) A stiff-man with malabsorption. J R Soc Med 81:115–117Google Scholar
  30. 30.
    Reis DJ (1987) Neurotransmitters acting in the C1 area in the tonic and reflex control of blood pressure. J Cardiovasc Pharmacol 10 [Suppl 12]:S22-S25Google Scholar
  31. 31.
    Relkin R (1966) Death following withdrawal of diazepam. NY State J Med 66:1770–1772Google Scholar
  32. 32.
    Schmidt RT, Stahl SM, Spehlmann R (1975) A pharmacologic study of the stiff-man syndrome. Neurology 25:622–626Google Scholar
  33. 33.
    Solimena M, Folli F, Denis-Donini S, Comi GC, Pozza G, De Camilli P, Vicari AM (1988) Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy and type I diabetes mellitus. N Engl J Med 318:1012–1020Google Scholar
  34. 34.
    Solimena M, Folli F, Morello F, Toso V, De Camilli P (1990) Autoantibodies directed against GABA-ergic synapses in a second case of stiff-man syndrome and epilepsy. In: Berardelli A, Beneicke R, Manfredi M, Marsden CD (eds) Motor disturbances II. Academic Press, New York (in press)Google Scholar
  35. 35.
    Solimena M, Folli F, Aparisi R, Pozza G, De Camilli P (1990) Autoantibodies GABA-ergic neurons and pancreatic beta-cells in stiff-man syndrome. N Engl J Med 322:1555–1560Google Scholar
  36. 36.
    Stuart FS, Henry M, Holley HL (1960) The stiff-man syndrome: report of a case. Arthritis Rheum 3:229–232Google Scholar
  37. 37.
    Tourtellotte WW, Walsh MJ (1984) Cerebrospinal fluid profile in multiple sclerosis. In: Poser CM (ed) The diagnosis of multiple sclerosis. Thieme-Stratton, New York, pp 165–178Google Scholar
  38. 38.
    Trethowan WH, Allsop JL, Turner B (1960) The “stiff-man” syndrome: a report of two further cases. Arch Neurol 3:448–456Google Scholar
  39. 39.
    Watanabe K, Shimizu T, Mannen T, Toyokura Y, Nagashima K (1984) An autopsy case with unusual muscle rigidity resembling stiff-man syndrome. Clin Neurol (Tokyo) 24:839–847Google Scholar
  40. 40.
    Whiteley AM, Swash M, Urich H (1976) Progressive encephalomyelitis with rigidity. Brain 99:27–42Google Scholar
  41. 41.
    Williams AC, Nutt JG, Hare T (1988) Autoimmunity in stiffman syndrome. Lancet II:222Google Scholar
  42. 42.
    Yamada KA, McAllen RM, Loewy AD (1984) GABA antagonist applied to the ventral surface of the medulla oblongata blocking the baroreceptor reflex. Brain Res 297:175–180Google Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Hiroshi Mitsumoto
    • 1
  • Michael J. Schwartzman
    • 1
  • Melinda L. Estes
    • 2
  • Samuel M. Chou
    • 2
  • Eugene F. La Franchise
    • 1
  • Pietro De Camilli
    • 3
  • Michele Solimena
    • 3
  1. 1.Department of NeurologyThe Cleveland Clinic FoundationClevelandUSA
  2. 2.Department of PathologyThe Cleveland Clinic FoundationClevelandUSA
  3. 3.Department of Cell BiologyYale University Medical SchoolNew HavenUSA

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