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Stiff-Person Syndrome: Autoimmunity and the Central Nervous System

Published online by Cambridge University Press:  07 November 2014

Beth Brianna Murinson  and
Angela Vincent
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Abstract

Stiff-person syndrome (SPS) is a rare disease of severe progressive muscle stiffness in the spine and lower extremities with superimposed muscle spasms triggered by external stimuli. Patients with SPS are often referred for psychiatric evaluation and the psychiatrist may be the first to diagnosis SPS. Psychosocial stressors often precede the first manifestations of the disease; depression, anxiety, and alcohol abuse are comorbid illnesses. The identification of an association with antibodies to glutamic acid decarboxylase (GAD) was invaluable for definitively establishing a pathological basis for the disease; antibodies to amphiphysin and gephyrin are also found in cases of SPS but at much lower frequencies. Whether the antibodies inhibit GAD activity in vivo, target GAD-expressing neurons for immune-mediated destruction, are part of a wider immune process, or are merely a marker for destruction of GAD-expressing neurons by an independent neurodegenerative process is not yet clear. Both electromyography and the detection of GAD antibodies are useful in establishing a diagnosis of SPS. Treatment of SPS includes the use of immunomodulating therapies (plasmapheresis and intravenous immunoglobulins) and symptomatic treatment with benzodiazepines and baclofen. The use of tricyclic antidepressants and rapid withdrawal from therapy should be avoided.

Type
Research Article
Information
CNS Spectrums , Volume 6 , Issue 5: Neuroimmunology , May 2001 , pp. 427 - 433
Copyright
Copyright © Cambridge University Press 2001

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References

REFERENCES

1.Tinsley, JA, Barth, EM, Black, JL, Williams, DE. Psychiatric consultations in stiff-man syndrome. J Clin Psychiatry. 1997;58(10):444–449.CrossRefGoogle ScholarPubMed
2.Black, JL, Barth, EM, Williams, DE, Tinsley, JA. Stiff-man syndrome. Results of interviews and psychological testing. Psychosomatics. 1998;39(1):38–44.CrossRefGoogle Scholar
3.Henningsen, P, Clement, U, Kuchenhoff, J, Simon, F, Meinck, HM. Psychological factors in the diagnosis and pathogenesis of stiff-man syndrome. Neurology. 1996;47(1):38–42.CrossRefGoogle ScholarPubMed
4.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;31:421–427.Google ScholarPubMed
5.Gordon, EE, Januszko, DM, Kaufman, L. A critical survey of stiff-man syndrome. Am J Med. 1967;42(4):582–599.CrossRefGoogle ScholarPubMed
6.Lorish, TR, Thorsteinsson, G, Howard, FM. Stiff-man syndrome updated. Mayo Clin Proc. 1989;64(6):629–636.CrossRefGoogle ScholarPubMed
7.Blum, P, Jankovic, J. Stiff-person syndrome: an autoimmune disease. Mov Disord. 1991;6(1):12–20.CrossRefGoogle ScholarPubMed
8.Dalakas, MC, Fujii, M, Li, M, McElroy, B. The clinical spectrum of anti-GAD antibody-positive patients with stiff-person syndrome. Neurology. 2000;55(10):1531–1535.CrossRefGoogle ScholarPubMed
9.Howard, FM Jr.A new and effective drug in the treatment of the stiff-man syndrome: preliminary report. Mayo Clin Proc. 1963;38:203–212.Google ScholarPubMed
10.Whelan, JL. Baclofen in treatment of the ‘stiff-man’ syndrome. Arch Neurol. 1980;37(9):600–601.CrossRefGoogle ScholarPubMed
11.Vicari, AM, Folli, F, Pozza, G, et al.Plasmapheresis in the treatment of stiff-man syndrome. N Engl J Med. 1989;320(22):1499.Google ScholarPubMed
12.Solimena, M, Folli, F, Denis-Donini, S, et al.Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy, and type I diabetes mellitus. N Engl J Med. 1988;318(16):1012–1020.CrossRefGoogle Scholar
13.Folli, F, Solimena, M, Cofiell, R, et al.Autoantibodies to a 128-kd synaptic protein in three women with the stiff-man syndrome and breast cancer. N Engl J Med. 1993;328(8):546–551.CrossRefGoogle ScholarPubMed
14.Butler, MH, Hayashi, A, Ohkoshi, N, et al.Autoimmunity to gephyrin in stiff-man syndrome. Neuron. 2000;26(2):307–312.CrossRefGoogle ScholarPubMed
15.Solimena, M, Folli, F, Aparisi, R, Pozza, G, De Camilli, P. Autoantibodies to GABA-ergic neurons and pancreatic beta cells in stiff-man syndrome. N Engl J Med. 1990;322(22):1555–1560.CrossRefGoogle ScholarPubMed
16.Garzo, C, Perez-Sotelo, M, Traba, A, Esteban, A, Grandas, F, Munoz-Blanco, JL. Stiff-man syndrome in a child. Mov Disord. 1998;13(2):365–368.CrossRefGoogle ScholarPubMed
17.Brown, P, Rothwell, JC, Marsden, CD. The stiff leg syndrome. J Neurol Neurosurg Psychiatry. 1997;62(1):31–37.CrossRefGoogle ScholarPubMed
18.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;65(5):633–640.CrossRefGoogle ScholarPubMed
19.Brown, P, Marsden, CD. The stiff-man and stiff-man-plus syndromes. J Neurol. 1999;246(8):648–652.CrossRefGoogle ScholarPubMed
20.Darnell, RB, Victor, J, Rubin, M, Clouston, P, Plum, F. A novel antineuronal antibody in stiff-man syndrome. Neurology. 1993;43(1):114–120.CrossRefGoogle ScholarPubMed
21.Rosin, L, DeCamilli, P, Butler, M, et al.Stiff-man syndrome in a woman with breast cancer: an uncommon central nervous system paraneoplastic syndrome. Neurology. 1998;50(1):94–98.CrossRefGoogle Scholar
22.Murinson, BB. Stiff-man syndrome: GABA, GAD, and mechanisms of disease. The Neuroscientist 2000;6(3):147–150.CrossRefGoogle Scholar
23.Armon, C, McEvoy, KM, Westmoreland, BF, McManis, PG. Clinical neurophysiologic studies in stiff-man syndrome: use of simultaneous video-electroencephalographic-surface electromyographic recording. Mayo Clin Proc. 1990;65(7):960–967.CrossRefGoogle ScholarPubMed
24.Meinck, HM, Ricker, K, Hulser, PJ, Solimena, M. Stiff-man syndrome: neurophysiological findings in eight patients. J Neurol. 1995;242(3):134–142.CrossRefGoogle ScholarPubMed
25.Floeter, MK, Valls-Sole, J, Toro, C, Jacobowitz, D, Hallett, M. Physiologic studies of spinal inhibitory circuits in patients with stiff-person syndrome. Neurology. 1998;51(1):85–93.CrossRefGoogle ScholarPubMed
26.Logullo, F, Di Bella, P, Provinciali, L. Motor evoked potentials in a case of stiff-man syndrome: a longitudinal study. Ital J Neurol Sci. 1999;20(2):133–138.CrossRefGoogle Scholar
27.Sandbrink, F, Syed, NA, Fujii, MD, Dalakas, MC, Floeter, MK. Motor cortex excitability in stiff-person syndrome. Brain. 2000;123 (Pt 11):2231–2239.CrossRefGoogle ScholarPubMed
28.Pugliese, A, Solimena, M, Awdeh, ZL, et al.Association of HLA-DQB1*0201 with stiff-man syndrome. J Clin Endocrinol Metab. 1993;77(6):1550–1553.Google ScholarPubMed
29.Saiz, A, Arpa, J, Sagasta, A, et al.Autoantibodies to glutamic decarboxylase in three patients with cerebellar ataxia, late-onset insulin-dependent diabetes mellitus, polyendocrine autoimmunity. Neurology. 1997;49(4):1026–1030.CrossRefGoogle ScholarPubMed
30.Nemni, R, Braghi, S, Natali-Sora, MG, et al.Autoantibodies to glutamic acid decarboxylase in palatal myoclonus and epilepsy. Ann Neurol. 1994;36(4):665–667.CrossRefGoogle ScholarPubMed
31.Peltola, J, Kulmala, P, Isojarvi, J, et al.Autoantibodies to glutamic acid decarboxylase in patients with therapy-resistant epilepsy. Neurology. 2000;55(1):46–50.CrossRefGoogle ScholarPubMed
32.Kim, J, Namchuk, M, Bugawan, T, et al.Higher autoantibody levels and recognition of a linear NH2-terminal epitope in the autoantigen GAD65, distinguishing stiff-man syndrome from insulin-dependent diabetes mellitus. J Exp Med. 1994;180(2):595–606.CrossRefGoogle ScholarPubMed
33.Walikonis, JE, Lennon, VA. Radioimmunoassay for glutamic acid decarboxylase (GAD65) autoantibodies as a diagnostic aid for stiff-man syndrome and a correlate of susceptibility to type I diabetes mellitus. Mayo Clin Proc. 1998;73(12):1161–1166.CrossRefGoogle Scholar
34.Ishizawa, K, Komori, T, Okayama, K, et al.Large motor neuron involvement in stiff-man syndrome: a qualitative and quantitative study. Acta Neuropathol (Berl). 1999;97(1):63–70.CrossRefGoogle ScholarPubMed
35.Saiz, A, Minguez, A, Graus, F, et al.Stiff-man syndrome with vacuolar degeneration of anterior horn motor neurons. J Neurol. 1999;246(9):858–860.CrossRefGoogle ScholarPubMed
36.Mitoma, H, Song, SY, Ishida, K, et al.Presynaptic impairment of cerebellar inhibitory synapses by an autoantibody to glutamate decarboxylase. J Neurol Sci. 2000;175(1):40–44.CrossRefGoogle ScholarPubMed
37.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;44(2):194–201.CrossRefGoogle ScholarPubMed
38.Floyd, S, Butler, MH, Cremona, O, et al.Expression of amphiphysin I, an autoantigen of paraneoplastic neurological syndromes, in breast cancer. Mol Med. 1998;4(1):29–39.CrossRefGoogle ScholarPubMed
39.Dropcho, EJ. Antiamphiphysin antibodies with small-cell lung carcinoma and paraneoplastic encephalomyelitis. Ann Neurol. 1996;39(5):659–667.CrossRefGoogle ScholarPubMed
40.Saiz, A, Dalmau, J, Butler, MH, et al.Anti-amphiphysin I antibodies in patients with paraneoplastic neurological disorders associated with small-cell lung carcinoma. J Neurol Neurosurg Psychiatry. 1999;66(2):214–217.CrossRefGoogle ScholarPubMed
41.Vincent, A, Grimaldi, LM, Martino, G, Davenport, C, Todd, I. Antibodies to 1251-glutamic acid decarboxylase in patients with stiff-man syndrome. J Neurol Neurosurg Psychiatry. 1997;62(4):395–397.CrossRefGoogle ScholarPubMed
42.Amato, AA, Cornman, EW, Kissel, JT. Treatment of stiff-man syndrome with intravenous immunoglobulin. Neurology. 1994;44(9):1652–1654.CrossRefGoogle ScholarPubMed
43.Barker, RA, Marsden, CD. Successful treatment of stiff-man syndrome with intravenous immunoglobulin. J Neurol Neurosurg Psychiatry. 1997;62(4):426–427.CrossRefGoogle ScholarPubMed
44.Brashear, HR, Phillips, LH. Autoantibodies to GABAergic neurons and response to plasmapheresis in stiff-man syndrome. Neurology. 1991;41(10):1588–1592.CrossRefGoogle ScholarPubMed
45.Hao, W, Davis, C, Hirsch, IB, et al.Plasmapheresis and immunosuppression in stiff-man syndrome with type I diabetes: a 2-year study. J Neurol. 1999;246(8):731–735.CrossRefGoogle Scholar
46.Harding, AE, Thompson, PD, Kocen, RS, Batchelor, JR, Davey, N, Marsden, CD. Plasma exchange and immunosuppression in the stiffman syndrome. Lancet. 1989;2(8668):915.CrossRefGoogle Scholar
47.Karlson, EW, Sudarsky, L, Ruderman, E, Pierson, S, Scott, M, Helfgott, SM. Treatment of stiff-man syndrome with intravenous immune globulin. Arthritis Rheum. 1994;37(6):915–918.CrossRefGoogle ScholarPubMed
48.Khanlou, H, Eiger, G. Long-term remission of refractory stiff-man syndrome after treatment with intravenous immunoglobulin. Mayo Clin Proc. 1999;74(12):1231–1232.CrossRefGoogle ScholarPubMed
49.Nakamagoe, K, Ohkoshi, N, Hayashi, A, Hisahara, S, Shoji, S. Marked clinical improvement by plasmapheresis in a patient with stiff-man syndrome: a case with a negative anti-GAD antibody. Rinsho Shinkeigaku. 1995;35(8):897–900.Google Scholar
50.Sevrin, C, Moulin, T, Tatu, L, et al.“Stiff-man” syndrome treated with intravenous immunoglobulins. Rev Neurol (Paris). 1998;154(5):431.Google ScholarPubMed
51.Souza-Lima, CF, Ferraz, HB, Braz, CA, Araujo, AM, Manzano, GM. Marked improvement in a stiff-limb patient treated with intravenous immunoglobulin. Mov Disord. 2000;15(2):358–359.3.0.CO;2-L>CrossRefGoogle Scholar
52.Vieregge, P, Branczyk, B, Barnett, W, Stocker, W, Soyka, D, Kompf, D. Stiff-man syndrome. Report of 4 cases. Nervenarzt. 1994;65(10):712–717.Google ScholarPubMed
53.Westblom, U. Stiff-man syndrome and clonazepam. JAMA. 1977;237(18):1930.CrossRefGoogle ScholarPubMed
54.Miller, F, Korsvik, H. Baclofen in the treatment of stiff-man syndrome. Ann Neurol. 1981;9(5):511–512.CrossRefGoogle ScholarPubMed
55.Silbert, PL, Matsumoto, JY, McManis, PG, et al.Intrathecal baclofen therapy in stiff-man syndrome: a double-blind, placebo-controlled trial. Neurology. 1995;45(10):1893–1897.CrossRefGoogle ScholarPubMed
56.Meinck, HM, Tronnier, V, Rieke, K, et al.Intrathecal baclofen treatment for stiff-man syndrome: pump failure may be fatal. Neurology. 1994;44(11):2209–2210.CrossRefGoogle ScholarPubMed
57.Prevett, MC, Brown, P, Duncan, JS. Improvement of stiff-man syndrome with vigabatrin. Neurology. 1997;48(4):1133–1134.CrossRefGoogle ScholarPubMed
58.Vermeij, FH, van Doom, PA, Busch, HF. Improvement of stiff-man syndrome with vigabatrin. Lancet. 1996;348(9027):612.CrossRefGoogle ScholarPubMed
59.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):280–287.CrossRefGoogle ScholarPubMed
60.Goetz, CG, Klawans, HL. On the mechanism of sudden death in Moersch-Woltman syndrome. Neurology. 1983;33(7):930–932.CrossRefGoogle ScholarPubMed
61.Maccario, M, Baugh, JR, Mena, H. Sudden death in Moersch-Woltman. Neurology. 1984;34(3):407.CrossRefGoogle ScholarPubMed
62.Mitsumoto, H, Schwartzman, MJ, Estes, ML, et al.Sudden death and paroxysmal autonomic dysfunction in stiff-man syndrome. J Neural. 1991;238(2):91–96.CrossRefGoogle ScholarPubMed