Summary
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.
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References
Asher R (1958) A woman with stiff-man syndrome. Br Med J I:265–266
Campbell AMG, Garland H (1956) Subacute myoclonic spinal neuronitis. J Neurol Neurosurg Psychiatry 19:268–274
Cohen L (1966) Stiff-man syndrome: two patients treated with diazepam. JAMA 195:222–224
Drake ME Jr (1983) Stiff-man syndrome and dementia. Am J Med 74:1085–1087
Finckle BS, McCloskey KL, Goodman LS (1979) Diazepam and drug-associated deaths: a survey in the United States and Canada. JAMA 242:429–434
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 32:488
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 310:1511–1513
Goetz CG, Klawans HL (1983) On the mechanism of sudden death in Moersch-Woltman syndrome. Neurology 33:930–932
Gordon EE, Januszko DM, Kaufman L (1967) A critical survey of stiff-man syndrome. Am J Med 42:582–599
Guilleminault J, Sigwald J, Castaigne E (1973) Sleep studies and therapeutic trial with L-dopa in a case of stiff-man syndrome. Eur Neurol 10:89–96
Howard FM Jr (1963) A new and effective drug in the treatment of stiff-man syndrome: preliminary report. Mayo Clin Proc 38:203–212
Howell DA, Lees AJ, Toghill PJ (1979) Spinal internuncial neurones in progressive encephalomyelitis with rigidity. J Neurol Neurosurg Psychiatry 42:773–785
Jay GW, Leestma JE (1981) Sudden death in epilepsy. Acta Neurol Scand 63 [Suppl 82]:1–66
Kasperek S, Zebrowski S (1971) Stiff-man syndrome and encephalomyelitis: report of a case. Arch Neurol 24:22–30
Laskey W, Polosa C (1988) Characteristics of the sympathetic pre-ganglionic neurons and its synaptic input. Proc Neurobiol 31:47–84
Lathers CM, Schraeder PL (1982) Autonomic dysfunction in epilepsy. Epilepsia 23:633–647
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) 128:3–21
Lorish TR, Thorsteinsson G, Howard FM Jr (1989) Stiff-man syndrome updated. Mayo Clin Proc 64:629–636
Maccario M, Blaugh JR, Mena H (1984) Sudden death in Moersch-Woltman syndrome. Neurology 34:407
Maida E, Reisner T, Summer K, Sandor-Eggerth H (1980) Stiff-man syndrome with abnormalities in CSF and computerized tomography findings. Arch Neurol 37:182–183
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 41:458–462
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) 138:502–505
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 31:421–427
Nakamura N, Fujiya S, Yahara O, Fujioka Y, Kawakami Y (1986) Stiff-man syndrome with spinal cord lesion. Clin Neuropathol 5:40–46
Norris JW (1983) Effects of cerebrovascular lesions on the heart. Neurol Clin 1:87–101
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 39:131–144
Piccolo G, Cosi V (1989) Stiff-man syndrome, dysimmune disorder, and cancer. Ann Neurol 26:105
Primhak RA, Spicer RD, Variend S (1986) Sudden death after minor abdominal trauma: an unusual presentation of pheochromocytoma. Br J Med 292:95–96
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 81:115–117
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-S25
Relkin R (1966) Death following withdrawal of diazepam. NY State J Med 66:1770–1772
Schmidt RT, Stahl SM, Spehlmann R (1975) A pharmacologic study of the stiff-man syndrome. Neurology 25:622–626
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 318:1012–1020
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)
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 322:1555–1560
Stuart FS, Henry M, Holley HL (1960) The stiff-man syndrome: report of a case. Arthritis Rheum 3:229–232
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 165–178
Trethowan WH, Allsop JL, Turner B (1960) The “stiff-man” syndrome: a report of two further cases. Arch Neurol 3:448–456
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) 24:839–847
Whiteley AM, Swash M, Urich H (1976) Progressive encephalomyelitis with rigidity. Brain 99:27–42
Williams AC, Nutt JG, Hare T (1988) Autoimmunity in stiffman syndrome. Lancet II:222
Yamada KA, McAllen RM, Loewy AD (1984) GABA antagonist applied to the ventral surface of the medulla oblongata blocking the baroreceptor reflex. Brain Res 297:175–180
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Mitsumoto, H., Schwartzman, M.J., Estes, M.L. et al. Sudden death and paroxysmal autonomic dysfunction in stiff-man syndrome. J Neurol 238, 91–96 (1991). https://doi.org/10.1007/BF00315688
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DOI: https://doi.org/10.1007/BF00315688