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. 1998 Nov;65(5):633–640. doi: 10.1136/jnnp.65.5.633

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

R Barker 1, T Revesz 1, M Thom 1, C Marsden 1, P Brown 1
PMCID: PMC2170335  PMID: 9810930

Abstract

OBJECTIVE—To investigate whether the stiff limb syndrome may be separated from the stiff man syndrome and progressive encephalomyelitis with rigidity on simple clinical grounds, and whether such a distinction has implications for aetiology, treatment, and prognosis.
METHODS— Twenty three patients referred over a 10 year period with rigidity and spasms in association with continuous motor unit activity, but without evidence of neuromyotonia, extrapyramidal or pyramidal dysfunction or focal lesions of the spinal cord were reviewed. The patients were divided into those with an acute or subacute illness, leading to death within 1 year, and those with a chronic course. The latter were divided into those in whom rigidity and spasms dominated in the axial muscles, or in one or more distal limbs, at the time of their first assessment.
RESULTS—This simple division identified three distinct groups of patients. (1) Progressive encephalomyelitis with rigidity: two patients had a rapidly progressive condition characterised by widespread rigidity which resulted in death within 6 and 16 weeks. One patient had negative anti-GAD and anti-neuronal antibodies, but had markedly abnormal CSF and widespread denervation. The principal pathological findings in this case were a subacute encephalomyelitis which primarily affected the grey matter. In the remaining patient anti-GAD antibodies were not tested, and postmortem was refused. (2) Stiff man syndrome: eight patients had rigidity and painful spasms of the lumbar paraspinal, abdominal, and occasionally proximal leg muscles associated with a lumbar hyperlordosis. There was no involvement of the upper limbs, distal lower limbs, sphincters or cranial nerves. Seven had anti-GAD antibodies and most had additional evidence of autoimmune disease. Neurophysiologically there was continuous motor unit activity with abnormal exteroceptive reflexes, but a normal interference pattern during spasms. The patients all responded to baclofen/diazepam and remained ambulant. (3) Stiff limb syndrome: thirteen patients had rigidity, painful spasm, and abnormal postures of the distal limb, usually the leg. About half went on to develop sphincter or brainstem involvement. Generalised myoclonic jerks were not a feature. Only two had truncal rigidity, and another two had anti-GAD antibodies. Most had no evidence of autoimmune disease. Neurophysiologically they had continuous motor unit activity in the affected limb, abnormal exteroceptive reflexes, and abnormally segmented EMG activity during spasms. The disease ran a protracted course, and most patients had only a partial response to baclofen or diazepam. About half became wheelchair bound.
CONCLUSIONS—The stiff limb syndrome seems distinct from the stiff man syndrome or progressive encephalomyelitis with rigidity, and is an important cause of rigidity and spasm in the setting of continuous motor unit activity.



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Selected References

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  1. Armon C., Swanson J. W., McLean J. M., Westbrook P. R., Okazaki H., Kurtin P. J., Kalyan-Raman U. P., Rodriguez M. Subacute encephalomyelitis presenting as stiff-person syndrome: clinical, polygraphic, and pathologic correlations. Mov Disord. 1996 Nov;11(6):701–709. doi: 10.1002/mds.870110616. [DOI] [PubMed] [Google Scholar]
  2. Barker R. A., Marsden C. D. Successful treatment of stiff man syndrome with intravenous immunoglobulin. J Neurol Neurosurg Psychiatry. 1997 Apr;62(4):426–427. doi: 10.1136/jnnp.62.4.426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brown P., Rothwell J. C., Marsden C. D. The stiff leg syndrome. J Neurol Neurosurg Psychiatry. 1997 Jan;62(1):31–37. doi: 10.1136/jnnp.62.1.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burn D. J., Ball J., Lees A. J., Behan P. O., Morgan-Hughes J. A. A case of progressive encephalomyelitis with rigidity and positive antiglutamic acid decarboxylase antibodies [corrected]. J Neurol Neurosurg Psychiatry. 1991 May;54(5):449–451. doi: 10.1136/jnnp.54.5.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. CAMPBELL A. M., GARLAND H. Subacute myoclonic spinal neuronitis. J Neurol Neurosurg Psychiatry. 1956 Nov;19(4):268–274. doi: 10.1136/jnnp.19.4.268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dalmau J., Graus F., Rosenblum M. K., Posner J. B. Anti-Hu--associated paraneoplastic encephalomyelitis/sensory neuronopathy. A clinical study of 71 patients. Medicine (Baltimore) 1992 Mar;71(2):59–72. doi: 10.1097/00005792-199203000-00001. [DOI] [PubMed] [Google Scholar]
  7. Daw K., Ujihara N., Atkinson M., Powers A. C. Glutamic acid decarboxylase autoantibodies in stiff-man syndrome and insulin-dependent diabetes mellitus exhibit similarities and differences in epitope recognition. J Immunol. 1996 Jan 15;156(2):818–825. [PubMed] [Google Scholar]
  8. De Camilli P., Thomas A., Cofiell R., Folli F., Lichte B., Piccolo G., Meinck H. M., Austoni M., Fassetta G., Bottazzo G. The synaptic vesicle-associated protein amphiphysin is the 128-kD autoantigen of Stiff-Man syndrome with breast cancer. J Exp Med. 1993 Dec 1;178(6):2219–2223. doi: 10.1084/jem.178.6.2219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dropcho E. J. Antiamphiphysin antibodies with small-cell lung carcinoma and paraneoplastic encephalomyelitis. Ann Neurol. 1996 May;39(5):659–667. doi: 10.1002/ana.410390516. [DOI] [PubMed] [Google Scholar]
  10. Fenzi F., Bongiovanni G., Fincati E., Pampanin M., Tomelleri G., Rizzuto N. Anatomical and clinical study of a case of subacute encephalomyelitis with hyperekplexia syndrome. Ital J Neurol Sci. 1988 Oct;9(5):505–508. doi: 10.1007/BF02337170. [DOI] [PubMed] [Google Scholar]
  11. Folli F., Solimena M., Cofiell R., Austoni M., Tallini G., Fassetta G., Bates D., Cartlidge N., Bottazzo G. F., Piccolo G. Autoantibodies to a 128-kd synaptic protein in three women with the stiff-man syndrome and breast cancer. N Engl J Med. 1993 Feb 25;328(8):546–551. doi: 10.1056/NEJM199302253280805. [DOI] [PubMed] [Google Scholar]
  12. Gordon E. E., Januszko D. M., Kaufman L. A critical survey of stiff-man syndrome. Am J Med. 1967 Apr;42(4):582–599. doi: 10.1016/0002-9343(67)90057-5. [DOI] [PubMed] [Google Scholar]
  13. Grimaldi L. M., Martino G., Braghi S., Quattrini A., Furlan R., Bosi E., Comi G. Heterogeneity of autoantibodies in stiff-man syndrome. Ann Neurol. 1993 Jul;34(1):57–64. doi: 10.1002/ana.410340111. [DOI] [PubMed] [Google Scholar]
  14. Howell D. A., Lees A. J., Toghill P. J. Spinal internuncial neurones in progressive encephalomyelitis with rigidity. J Neurol Neurosurg Psychiatry. 1979 Sep;42(9):773–785. doi: 10.1136/jnnp.42.9.773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kasperek S., Zebrowski S. Stiff-man syndrome and encephalomyelitis. Report of a case. Arch Neurol. 1971 Jan;24(1):22–30. doi: 10.1001/archneur.1971.00480310050004. [DOI] [PubMed] [Google Scholar]
  16. Leigh P. N., Rothwell J. C., Traub M., Marsden C. D. A patient with reflex myoclonus and muscle rigidity: "jerking stiff-man syndrome". J Neurol Neurosurg Psychiatry. 1980 Dec;43(12):1125–1131. doi: 10.1136/jnnp.43.12.1125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lhermitte F., Chain F., Escourolle R., Chedru F., Guilleminault C., Francoual M. Un nouveau cas de contracture tétaniforme distinct "du stiff man syndrome". Etude pharmacologique et neuropathologique d'un cas d'encéphalomyélite à prédominance médullaire. Rev Neurol (Paris) 1973 Jan;128(1):3–21. [PubMed] [Google Scholar]
  18. Lorish T. R., Thorsteinsson G., Howard F. M., Jr Stiff-man syndrome updated. Mayo Clin Proc. 1989 Jun;64(6):629–636. doi: 10.1016/s0025-6196(12)65339-7. [DOI] [PubMed] [Google Scholar]
  19. MOERSCH F. P., WOLTMAN H. W. Progressive fluctuating muscular rigidity and spasm ("stiff-man" syndrome); report of a case and some observations in 13 other cases. Proc Staff Meet Mayo Clin. 1956 Jul 25;31(15):421–427. [PubMed] [Google Scholar]
  20. Prevett M. C., Brown P., Duncan J. S. Improvement of stiff-man syndrome with vigabatrin. Neurology. 1997 Apr;48(4):1133–1134. doi: 10.1212/wnl.48.4.1133-a. [DOI] [PubMed] [Google Scholar]
  21. RUSHWORTH G., LISHMAN W. A., HUGHES J. T., OPPENHEIMER D. R. Intense rigidity of the arms due to isolation of motoneurones by a spinal tumour. J Neurol Neurosurg Psychiatry. 1961 May;24:132–142. doi: 10.1136/jnnp.24.2.132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Roobol T. H., Kazzaz B. A., Vecht C. J. Segmental rigidity and spinal myoclonus as a paraneoplastic syndrome. J Neurol Neurosurg Psychiatry. 1987 May;50(5):628–631. doi: 10.1136/jnnp.50.5.628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Roobol T. H., Kazzaz B. A., Vecht C. J. Segmental rigidity and spinal myoclonus as a paraneoplastic syndrome. J Neurol Neurosurg Psychiatry. 1987 May;50(5):628–631. doi: 10.1136/jnnp.50.5.628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. SIKES Z. S. Stiff-man syndrome; analysis and case report with spinal cord autopsy. Dis Nerv Syst. 1959 Jun;20(6):254–258. [PubMed] [Google Scholar]
  25. 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 May 31;322(22):1555–1560. doi: 10.1056/NEJM199005313222202. [DOI] [PubMed] [Google Scholar]
  26. TRETHOWAN W. H., ALLSOP J. L., TURNER B. The "stiff-man" syndrome. A report of two further cases. Arch Neurol. 1960 Oct;3:448–456. doi: 10.1001/archneur.1960.00450040098012. [DOI] [PubMed] [Google Scholar]
  27. Tarlov I. M. Rigidity in man due to spinal interneuron loss. Arch Neurol. 1967 May;16(5):536–543. doi: 10.1001/archneur.1967.00470230088012. [DOI] [PubMed] [Google Scholar]
  28. Whiteley A. M., Swash M., Urich H. Progressive encephalomyelitis with rigidity. Brain. 1976 Mar;99(1):27–42. doi: 10.1093/brain/99.1.27. [DOI] [PubMed] [Google Scholar]

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