stiff person syndrome

Summary

Summary: A condition characterized by persistent spasms (SPASM) involving multiple muscles, primarily in the lower limbs and trunk. The illness tends to occur in the fourth to sixth decade of life, presenting with intermittent spasms that become continuous. Minor sensory stimuli, such as noise and light touch, precipitate severe spasms. Spasms do not occur during sleep and only rarely involve cranial muscles. Respiration may become impaired in advanced cases. (Adams et al., Principles of Neurology, 6th ed, p1492; Neurology 1998 Jul;51(1):85-93)

Top Publications

  1. Dalakas M. Advances in the pathogenesis and treatment of patients with stiff person syndrome. Curr Neurol Neurosci Rep. 2008;8:48-55 pubmed
    Advances in the clinical diagnosis, prognosis, pathogenesis, and therapies for stiff person syndrome (SPS), based on observations in more than 50 consecutive patients, are presented...
  2. Murinson B, Butler M, Marfurt K, Gleason S, De Camilli P, Solimena M. Markedly elevated GAD antibodies in SPS: effects of age and illness duration. Neurology. 2004;63:2146-8 pubmed
    ..RIA did not correlate with age or illness duration. Marked elevations of RIA for GAD antibodies were characteristic of ICC-confirmed SPS, and modest elevations were not...
  3. Ameli R, Snow J, Rakocevic G, Dalakas M. A neuropsychological assessment of phobias in patients with stiff person syndrome. Neurology. 2005;64:1961-3 pubmed
    A neuropsychological assessment was performed in 10 patients with stiff person syndrome (SPS) to determine whether their anxiety and phobic symptoms precede stiffness and spasms or represent a reaction to disability...
  4. Baker M, Das M, Isaacs J, Fawcett P, Bates D. Treatment of stiff person syndrome with rituximab. J Neurol Neurosurg Psychiatry. 2005;76:999-1001 pubmed
    ..is about the novel use of the anti-CD20 antibody, rituximab, in the treatment of a 41 year old woman with stiff person syndrome. She was admitted to hospital as an emergency with prolonged and painful extensor spasms affecting the ..
  5. Raju R, Foote J, Banga J, Hall T, Padoa C, Dalakas M, et al. Analysis of GAD65 autoantibodies in Stiff-Person syndrome patients. J Immunol. 2005;175:7755-62 pubmed
    ..A mAb (N-GAD65 mAb) recognizing this N-terminal epitope was successfully humanized to enhance its potential therapeutic value by reducing its overall immunogenicity...
  6. Jarius S, Stich O, Speck J, Rasiah C, Wildemann B, Meinck H, et al. Qualitative and quantitative evidence of anti-glutamic acid decarboxylase-specific intrathecal antibody synthesis in patients with stiff person syndrome. J Neuroimmunol. 2010;229:219-24 pubmed publisher
    The stiff person syndrome (SPS) is a CNS disorder of putative autoimmune aetiology, which is clinically characterized by severe rigidity and spasms...
  7. Skorstad G, Hestvik A, Torjesen P, Alvik K, Vartdal F, Vandvik B, et al. GAD65 IgG autoantibodies in stiff person syndrome: clonality, avidity and persistence. Eur J Neurol. 2008;15:973-80 pubmed publisher
    Persistent intrathecal production of IgG autoantibodies against glutamic acid decarboxylase 65 (GAD65 IgG) and oligoclonal IgG of undetermined specificity has been reported in stiff person syndrome (SPS).
  8. Dalakas M, Li M, Fujii M, Jacobowitz D. Stiff person syndrome: quantification, specificity, and intrathecal synthesis of GAD65 antibodies. Neurology. 2001;57:780-4 pubmed
    To characterize the specificity of anti-GAD(65) antibodies in patients with stiff person syndrome (SPS), quantify antibody titers, and examine antibody production within the CNS.
  9. Levy L, Levy Reis I, Fujii M, Dalakas M. Brain gamma-aminobutyric acid changes in stiff-person syndrome. Arch Neurol. 2005;62:970-4 pubmed

More Information

Publications62

  1. Bouw J, Leendertse K, Tijssen M, Dzoljic M. Stiff person syndrome and anesthesia: case report. Anesth Analg. 2003;97:486-7, table of contents pubmed
    ..the successful perioperative management of a patient with a rare and disabling neurologic disorder, the stiff person syndrome. The patient had a delayed emergence despite apparent full reversal of neuromuscular blockade...
  2. Butler M, Hayashi A, Ohkoshi N, Villmann C, Becker C, Feng G, et al. Autoimmunity to gephyrin in Stiff-Man syndrome. Neuron. 2000;26:307-12 pubmed
    ..Our findings provide new evidence for a close link between autoimmunity directed against components of inhibitory synapses and neurological conditions characterized by chronic rigidity and spasms...
  3. Rizzi M, Knoth R, Hampe C, Lorenz P, Gougeon M, Lemercier B, et al. Long-lived plasma cells and memory B cells produce pathogenic anti-GAD65 autoantibodies in Stiff Person Syndrome. PLoS ONE. 2010;5:e10838 pubmed publisher
    b>Stiff person syndrome (SPS) is a rare, neurological disorder characterized by sudden cramps and spasms...
  4. Dalakas M. The role of IVIg in the treatment of patients with stiff person syndrome and other neurological diseases associated with anti-GAD antibodies. J Neurol. 2005;252 Suppl 1:I19-25 pubmed
    High-titre anti-GAD antibodies are characteristically seen in patients with stiff person syndrome (SPS)...
  5. Petzold G, Marcucci M, Butler M, van Landeghem F, Einhaupl K, Solimena M, et al. Rhabdomyolysis and paraneoplastic stiff-man syndrome with amphiphysin autoimmunity. Ann Neurol. 2004;55:286-90 pubmed
    ..Immunotherapy induced a remission of both rhabdomyolysis and SMS symptoms. Autoimmune rhabdomyolysis may represent a paraneoplastic complication of cancer patients with amphiphysin autoimmunity...
  6. Ledowski T, Russell P. Anaesthesia for stiff person syndrome: successful use of total intravenous anaesthesia. Anaesthesia. 2006;61:725 pubmed
  7. Geis C, Weishaupt A, Hallermann S, Grünewald B, Wessig C, Wultsch T, et al. Stiff person syndrome-associated autoantibodies to amphiphysin mediate reduced GABAergic inhibition. Brain. 2010;133:3166-80 pubmed publisher
    ..Symptoms consistent with reduced inhibition such as stiffness, spasms and anxiety occur in paraneoplastic stiff person syndrome with autoantibodies against the intracellular synaptic protein amphiphysin...
  8. Holmøy T, Skorstad G, Røste L, Scheie D, Alvik K. Stiff person syndrome associated with lower motor neuron disease and infiltration of cytotoxic T cells in the spinal cord. Clin Neurol Neurosurg. 2009;111:708-12 pubmed publisher
    ..To our knowledge, this is the first report of stiff person syndrome with lower motor signs restricted to a lower limb, and also the first attempt to characterize the ..
  9. Duddy M, Baker M. Stiff person syndrome. Front Neurol Neurosci. 2009;26:147-65 pubmed publisher
    b>Stiff person syndrome (SPS), stiff limb syndrome, jerking SPS and progressive encephalomyelitis with rigidity and myoclonus (PERM) are a family of rare, insidiously progressive diseases of the central nervous system...
  10. Elkassabany N, Tetzlaff J, Argalious M. Anesthetic management of a patient with stiff person syndrome. J Clin Anesth. 2006;18:218-20 pubmed
    ..The use of general anesthesia in patients with SPS carries the risk of postoperative hypotonia due to enhancement of gamma-aminobutyric acid action on synaptic transmission by drugs that have a gamma-aminobutyric acid agonistic action...
  11. Raju R, Hampe C. Immunobiology of stiff-person syndrome. Int Rev Immunol. 2008;27:79-92 pubmed publisher
    ..Clin. Neuropathol. 16: 214-219, 1997; Ishizawa et al., Acta Neuropathol.(Berl) 97: 63-70, 1999]. This review discusses the possible role of autoantibodies and autoreactive T cells specific to neuronal antigens in SPS pathogenesis...
  12. Rakocevic G, Raju R, Semino Mora C, Dalakas M. Stiff person syndrome with cerebellar disease and high-titer anti-GAD antibodies. Neurology. 2006;67:1068-70 pubmed
    We report five of 38 patients with stiff person syndrome (SPS), who also had cerebellar disease, gait ataxia, dysarthria, and oculomotor dysfunction (SPS-Cer). Cerebellar manifestations either preceded SPS or occurred concurrently...
  13. Dalakas M, Fujii M, Li M, Lutfi B, Kyhos J, McElroy B. High-dose intravenous immune globulin for stiff-person syndrome. N Engl J Med. 2001;345:1870-6 pubmed
    ..Because stiff-person syndrome is most likely immune-mediated, we evaluated the efficacy of intravenous immune globulin...
  14. Levy L, Dalakas M, Floeter M. The stiff-person syndrome: an autoimmune disorder affecting neurotransmission of gamma-aminobutyric acid. Ann Intern Med. 1999;131:522-30 pubmed
    ..Results of an ongoing controlled trial will elucidate the role of these agents in the treatment of the disease...
  15. Thomas S, Critchley P, Lawden M, Farooq S, Thomas A, Proudlock F, et al. Stiff person syndrome with eye movement abnormality, myasthenia gravis, and thymoma. J Neurol Neurosurg Psychiatry. 2005;76:141-2 pubmed
  16. Lim M, Beake J, Bible E, Curran T, Ramirez Montealegre D, Pearce D, et al. Distinct patterns of serum immunoreactivity as evidence for multiple brain-directed autoantibodies in juvenile neuronal ceroid lipofuscinosis. Neuropathol Appl Neurobiol. 2006;32:469-82 pubmed
    ..Moreover, sera from Stiff Person Syndrome and Type I Diabetes, disorders in which GAD65 autoantibodies are present, stained with profiles that were ..
  17. Chia S, Chua R, Lo Y, Wong M, Chan L, Tan E. Acute ataxia, Graves' disease, and stiff person syndrome. Mov Disord. 2007;22:1969-71 pubmed
    b>Stiff person syndrome (SPS) has been associated with autoimmune diseases, such as Type 1 diabetes mellitus and autoimmune thyroid disease (Hashimoto's thyroiditis), among others...
  18. Ohara K, Osawa M, Takeuchi M, Suzuki M, Uchiyama S, Iwata M. [Stiff-person syndrome with elevated anti-Epstein-Barr virus antibody]. Rinsho Shinkeigaku. 2007;47:434-6 pubmed
    ..However, a few cases of this syndrome associated with viral infection were recently reported and viral gene mimicity with GAD has been postulated. Viral infection might be considered as a probable cause of this syndrome...
  19. Ozer S, Ozcan H, Dinç G, Ertugrul A, Rezaki M, Ulusahin A. [Two stiff person cases misdiagnosed as conversion disorder]. Turk Psikiyatri Derg. 2009;20:392-7 pubmed
  20. Westerlund A, Ankelo M, Ilonen J, Knip M, Simell O, Hinkkanen A. Absence of avidity maturation of autoantibodies to the protein tyrosine phosphatase-like IA-2 molecule and glutamic acid decarboxylase (GAD65) during progression to type 1 diabetes. J Autoimmun. 2005;24:153-67 pubmed
    ..Our results indicate that the analysis of the avidity index levels of IA-2A and GADA does not improve the accuracy of the prediction of type 1 diabetes based on autoantibody detection...
  21. Ryan S, Dixon M, Nigro M, Kelts K, Markand O, Terry J, et al. Genetic and radiation hybrid mapping of the hyperekplexia region on chromosome 5q. Am J Hum Genet. 1992;51:1334-43 pubmed
    ..RH mapping eliminated the candidate genes GABRA1 and GABRG2, which encode GABA-A receptor components, by showing that they are telomeric to the target region...
  22. Zivotofsky A, Siman Tov T, Gadoth N, Gordon C. A rare saccade velocity profile in Stiff-Person Syndrome with cerebellar degeneration. Brain Res. 2006;1093:135-40 pubmed
    ..In addition, this unusual saccadic velocity profile may have important implications for modeling the saccadic system and furthering a complete understanding of saccade generation...
  23. Pittock S, Lucchinetti C, Parisi J, Benarroch E, Mokri B, Stephan C, et al. Amphiphysin autoimmunity: paraneoplastic accompaniments. Ann Neurol. 2005;58:96-107 pubmed
    ..01). Overall, a minority of women (39%) and men (12%) had stiff-man phenomena. Only 10% of women (some with lung carcinoma) and 4% of men fulfilled diagnostic criteria for stiff-man syndrome...
  24. Matsumoto S, Kusuhara T, Nakajima M, Ouma S, Takahashi M, Yamada T. Acute attacks and brain stem signs in a patient with glutamic acid decarboxylase autoantibodies. J Neurol Neurosurg Psychiatry. 2002;73:345-6 pubmed
  25. Ramirez Montealegre D, Chattopadhyay S, Curran T, Wasserfall C, Pritchard L, Schatz D, et al. Autoimmunity to glutamic acid decarboxylase in the neurodegenerative disorder Batten disease. Neurology. 2005;64:743-5 pubmed
    ..Batten patients did not possess autoantibodies against other type 1 diabetes-associated autoantigens and human leukocyte antigen genotypes revealed no specific associations with this disease...
  26. Cerimagic D, Bilic E. [Stiff person syndrome (Moersch-Woltman)]. Lijec Vjesn. 2010;132:110-4 pubmed
    ..scientific points in epidemiology, genetics, pathogenesis, clinical course and therapeutic strategies in stiff person syndrome (SPS). This syndrome is characterized by progressive muscle rigidity and painful muscle spasms...
  27. Ughratdar I, Sivakumar G, Basu S. Spinal cord stimulation to abort painful spasms of atypical stiff limb syndrome. Stereotact Funct Neurosurg. 2010;88:183-6 pubmed publisher
    ..We provide a brief overview of SLS and propose an underlying mechanism for the observed phenomenon...
  28. Brindle N. Premenstrual syndrome: a plea for greater understanding. J Fam Plann Reprod Health Care. 2006;32:256 pubmed
  29. Andreadou E, Kattoulas E, Sfagos C, Vassilopoulos D. Stiff person syndrome: avoiding misdiagnosis. Neurol Sci. 2007;28:35-7 pubmed
    b>Stiff person syndrome (SPS) is a rare neurological disorder characterised by muscular rigidity and superimposed spasms of the trunk and limbs that may be precipitated by voluntary movements and unexpected tactile, auditory or emotional ..
  30. Guardado Santervas P, Arjona Padillo A, Serrano Castro P, Olivares Romero J, Rubi Callejon J, Alonso Verdegay G, et al. Stiff person syndrome (SPS), a basal ganglia disease? Striatal MRI lesions in a patient with SPS. J Neurol Neurosurg Psychiatry. 2007;78:657-9 pubmed
  31. Thompson P. The stiff-man syndrome and related disorders. Parkinsonism Relat Disord. 2001;8:147-53 pubmed
    ..Fasciculations, myokymia, myotonia and complex repetitive discharges are characteristic of these peripheral neuromuscular disorders...
  32. Hayashi A, Nakamagoe K, Ohkoshi N, Hoshino S, Shoji S. Double filtration plasma exchange and immunoadsorption therapy in a case of stiff-man syndrome with negative anti-GAD antibody. J Med. 1999;30:321-7 pubmed
    ..The patient's improvement continued, but his condition declined again about ten months after plasma exchange. Immunoadsorption therapy was then performed, and this treatment was also effective...
  33. Bastin A, Gurmin V, Mediwake R, Gibbs J, Beynon H. Stiff man syndrome presenting with low back pain. Ann Rheum Dis. 2002;61:939-40 pubmed
  34. Hokari S, Koya T, Shimaoka Y, Nakayama H, Terada M, Suzuki E. [Interstitial pneumonia associated with stiff-person syndrome]. Nihon Kokyuki Gakkai Zasshi. 2010;48:162-5 pubmed
    ..He has needed continuous rehabilitation due to the progression of neurological symptoms despite the partial efficacy of anti-epilepsy agents. We report a case of interstitial pneumonia with stiff-person syndrome...
  35. Madaschi S, Rossini A, Formenti I, Lampasona V, Marzoli S, Cammarata G, et al. Treatment of thyroid-associated orbitopathy with rituximab--a novel therapy for an old disease: case report and literature review. Endocr Pract. 2010;16:677-85 pubmed publisher
    To report the use of rituximab to treat thyroid-associated orbitopathy (TAO) in a patient with a concomitant B-cell organ-specific autoimmune disorder-the stiff person syndrome (SPS).
  36. Shariatmadar S, Noto T. Plasma exchange in stiff-man syndrome. Ther Apher. 2001;5:64-7 pubmed
    ..Based on the results of PE in our patients, it seems that those who are autoantibody negative are less likely to respond. Whether a more aggressive approach to PE will be beneficial remains speculative...
  37. Pul R, Stangel M. Using immunoglobulins in muscular disease treatment. Expert Opin Biol Ther. 2008;8:1143-50 pubmed
    ..This led to the licensing and recommendation of IVIg as first-line treatment for Kawasaki disease, idiopathic thrombocytopenic purpura and Guillain-Barré syndrome...
  38. Saravanan P, Paul J, Sayeed Z. Stiff person syndrome and myasthenia gravis. Neurol India. 2002;50:98-100 pubmed
    Association of stiff person syndrome, an immune related disorder of anterior horn cells and myasthenia gravis an endplate disorder with similar pathogenesis, is rare...
  39. Vokatch N, Carota A, Annoni J, Aybek S. [Low back pain, muscle stiffness]. Rev Med Suisse. 2007;3:1191-2, 1194-5 pubmed
  40. Dubow J, Zadikoff C. Isolated navicular fracture presenting as stiff limb syndrome: a case report. Mov Disord. 2007;22:2136-7 pubmed
  41. Piovano C, Piattelli M, Spina T, Iervese G, Bosco G. The stiff-person syndrome. Case report. Minerva Anestesiol. 2002;68:861-5 pubmed
    ..Immunomodulatory agents such as steroids, plasmapheresis and intravenous immunoglobulin, seem to offer substantial improvement...
  42. O Sullivan E, Behan L, King T, Hardiman O, Smith D. A case of stiff-person syndrome, type 1 diabetes, celiac disease and dermatitis herpetiformis. Clin Neurol Neurosurg. 2009;111:384-6 pubmed publisher
    ..We discuss why SPS and type 1 diabetes co-exist in only a minority of cases and speculate on the underlying mechanism of the association with CD and dermatitis herpetiformis in our patient...
  43. Brune W, Weber R, Saul B, von Knebel Doeberitz M, Grond Ginsbach C, Kellerman K, et al. A GLRA1 null mutation in recessive hyperekplexia challenges the functional role of glycine receptors. Am J Hum Genet. 1996;58:989-97 pubmed
    ..This case demonstrates that, in contrast to the lethal effect of a null allele in the recessive mouse mutant oscillator (Glra1 spd-ot), the loss of the GlyR alpha 1 subunit is effectively compensated in man...
  44. Ergun I, Akbostanci M, Canbakan B, Koçer B, Ensari A, Nergizoglu G, et al. Minimal change nephrotic syndrome with stiff-person syndrome: is there a link?. Am J Kidney Dis. 2005;46:e11-4 pubmed
    ..To our knowledge, this is the first case of stiff-person syndrome in association with MCNS in the literature...
  45. Cantiniaux S, Azulay J, Boucraut J, Pouget J, Attarian S. [Stiff man syndrome: clinical forms, treatment and clinical course]. Rev Neurol (Paris). 2006;162:832-9 pubmed
    ..Stiff-Man syndrome (SMS) is a rare neurological disease first described fifty years ago. There are several clinical forms, which are frequently misdiagnosed. The aim of this study is to review three of the main clinical forms...
  46. Toothaker T, Rubin M. Paraneoplastic neurological syndromes: a review. Neurologist. 2009;15:21-33 pubmed publisher
    ..PNS are believed to result from an autoimmune attack of normal neuronal tissue, spurred by similar neuronal antigens ectopically expressed by tumor cells...
  47. Ho B, Shih P. Successful intrathecal baclofen therapy for seronegative stiff-person syndrome: a case report. Acta Neurol Taiwan. 2008;17:172-6 pubmed
    ..From our experience, we propose that intrathecal baclofen could be a considerable alternative treatment for patients with refractory stiff-person syndrome...
  48. Espay A, Chen R. Rigidity and spasms from autoimmune encephalomyelopathies: stiff-person syndrome. Muscle Nerve. 2006;34:677-90 pubmed
  49. Mares Segura R. [Spinal cord paraneoplastic syndromes]. Rev Neurol. 2000;31:1219-23 pubmed
    ..We reviewed the bibliography of various paraneoplastic syndromes which may show spinal involvement...
  50. Kiriakos C, Franco K. Stiff-man syndrome: a case report and review of the literature. Psychosomatics. 2002;43:243-4 pubmed
  51. Scavone G, Zaccardi F, Manto A, Caputo S, Pitocco D, Ghirlanda G. A case of chronic hepatitis C developing insulin-dependent diabetes, thyroid autoimmunity and stiff-person syndrome as complications of interferon therapy. Diabetes Res Clin Pract. 2010;89:e36-8 pubmed publisher
    ..This is the first reported case in which SPS has appeared as complication of IFNalpha therapy...
  52. Teggi R, Piccioni L, Martino G, Bellini C, Bussi M. Stiff-person syndrome with acute recurrent peripheral vertigo: possible evidence of gamma aminobutyric acid as a neurotransmitter in the vestibular periphery. J Laryngol Otol. 2008;122:636-8 pubmed
    ..We report a case of a 58-year-old man suffering from stiff-person syndrome and recurrent peripheral vertigo...
  53. Meinck H. Stiff man syndrome. CNS Drugs. 2001;15:515-26 pubmed
    ..For symptomatic treatment, the benzodiazepines are drugs of first choice. An alternative of last resort is baclofen administered intrathecally via an implanted pump device...