Advances in the Pathogenesis and Treatment of Patients with Stiff Person Syndrome

Overview

Journal Curr Neurol Neurosci Rep

Specialty Neurology

Date 2008 Mar 28

PMID 18367039

Citations 14

Authors

Marinos C Dalakas

Affiliations

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Abstract

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. The syndrome varies from mild to severe, but if untreated it can be progressive and disabling. SPS remains a largely underdiagnosed condition. Anti-glutamic acid decarboxylase (GAD) antibodies provide an excellent diagnostic marker, but their role in disease pathogenesis is uncertain. Research focused on identifying new autoantigens has provided evidence that gamma-aminobutyric acid (GABA)(A) receptor-associated protein (GABARAP), a 14-kD protein localized at the postsynaptic regions of GABAergic synapses, is a new antigenic target. In up to 65% of SPS patients, there are circulating anti-GABARAP antibodies that inhibit the GABA(A) receptor expression on GABAergic neurons. This review examines the diagnostic criteria for SPS, SPS variants, common errors in diagnosis, and a step-by-step therapeutic approach, including new advances in therapy.

Citing Articles

Emergent Anesthetic Management in a Patient Recently Diagnosed With Stiff Person Syndrome.

Pinto A, Dinis R, Godinho P, Carmona C Cureus. 2024; 16(10):e70899.

PMID: 39497870 PMC: 11534327. DOI: 10.7759/cureus.70899.

Prevalence, Clinical Profiles, and Prognosis of Stiff-Person Syndrome in a Japanese Nationwide Survey.

Matsui N, Tanaka K, Ishida M, Yamamoto Y, Matsubara Y, Saika R Neurol Neuroimmunol Neuroinflamm. 2023; 10(6).

PMID: 37739810 PMC: 10519438. DOI: 10.1212/NXI.0000000000200165.

A new perspective on the autophagic and non-autophagic functions of the GABARAP protein family: a potential therapeutic target for human diseases.

Chen J, Zhao H, Liu M, Chen L Mol Cell Biochem. 2023; 479(6):1415-1441.

PMID: 37440122 DOI: 10.1007/s11010-023-04800-5.

Stiff-person Syndrome and GAD Antibody-spectrum Disorders: GABAergic Neuronal Excitability, Immunopathogenesis and Update on Antibody Therapies.

Dalakas M Neurotherapeutics. 2022; 19(3):832-847.

PMID: 35084720 PMC: 9294130. DOI: 10.1007/s13311-022-01188-w.

GAD antibody-spectrum disorders: progress in clinical phenotypes, immunopathogenesis and therapeutic interventions.

Tsiortou P, Alexopoulos H, Dalakas M Ther Adv Neurol Disord. 2021; 14:17562864211003486.

PMID: 33854562 PMC: 8013924. DOI: 10.1177/17562864211003486.

References

Ameli R, Snow J, Rakocevic G, Dalakas M . A neuropsychological assessment of phobias in patients with stiff person syndrome. Neurology. 2005; 64(11):1961-3. DOI: 10.1212/01.WNL.0000163984.71993.FE. View

Barker R, Revesz T, Thom M, Marsden C, 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):633-40. PMC: 2170335. DOI: 10.1136/jnnp.65.5.633. View

Economides J, Horton J . Eye movement abnormalities in stiff person syndrome. Neurology. 2005; 65(9):1462-4. DOI: 10.1212/01.wnl.0000183068.42803.33. View

Levy L, Dalakas M, Floeter M . The stiff-person syndrome: an autoimmune disorder affecting neurotransmission of gamma-aminobutyric acid. Ann Intern Med. 1999; 131(7):522-30. DOI: 10.7326/0003-4819-131-7-199910050-00008. View

Whiteley A, Swash M, Urich H . Progressive encephalomyelitis with rigidity. Brain. 1976; 99(1):27-42. DOI: 10.1093/brain/99.1.27. View

Rakocevic G, Raju R, Semino-Mora C, Dalakas M . Stiff person syndrome with cerebellar disease and high-titer anti-GAD antibodies. Neurology. 2006; 67(6):1068-70. DOI: 10.1212/01.wnl.0000237558.83349.d0. View

Coyle J, Nikolov D . GABARAP: lessons for synaptogenesis. Neuroscientist. 2004; 9(3):205-16. DOI: 10.1177/1073858403009003013. View

Bouw J, Leendertse K, Tijssen M, Dzoljic M . Stiff person syndrome and anesthesia: case report. Anesth Analg. 2003; 97(2):486-487. DOI: 10.1213/01.ANE.0000072701.97699.79. View

Swen W, Jacobs J, Bussemaker F, de Waard J, Bijlsma J . Carpal tunnel sonography by the rheumatologist versus nerve conduction study by the neurologist. J Rheumatol. 2001; 28(1):62-9. View

10.

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(11):2146-8. DOI: 10.1212/01.wnl.0000145661.01675.a8. View

11.

Vulliemoz S, Vanini G, Truffert A, Chizzolini C, Seeck M . Epilepsy and cerebellar ataxia associated with anti-glutamic acid decarboxylase antibodies. J Neurol Neurosurg Psychiatry. 2007; 78(2):187-9. PMC: 2077657. DOI: 10.1136/jnnp.2006.089268. View

12.

Sharoqi I . Improvement of stiff-man syndrome with vigabatrin. Neurology. 1998; 50(3):833-4. DOI: 10.1212/wnl.50.3.833-a. View

13.

Dalakas M, Li M, Fujii M, Jacobowitz D . Stiff person syndrome: quantification, specificity, and intrathecal synthesis of GAD65 antibodies. Neurology. 2001; 57(5):780-4. DOI: 10.1212/wnl.57.5.780. View

14.

Ishida K, Mitoma H, Song S, Uchihara T, Inaba A, Eguchi S . Selective suppression of cerebellar GABAergic transmission by an autoantibody to glutamic acid decarboxylase. Ann Neurol. 1999; 46(2):263-7. View

15.

Raju R, Foote J, Banga J, Hall T, Padoa C, Dalakas M . Analysis of GAD65 autoantibodies in Stiff-Person syndrome patients. J Immunol. 2005; 175(11):7755-62. DOI: 10.4049/jimmunol.175.11.7755. View

16.

Dinkel K, Meinck H, Jury K, 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. DOI: 10.1002/ana.410440209. View

17.

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. 2002; 345(26):1870-6. DOI: 10.1056/NEJMoa01167. View

18.

Honnorat J, Saiz A, Giometto B, Vincent A, Brieva L, De Andres C . Cerebellar ataxia with anti-glutamic acid decarboxylase antibodies: study of 14 patients. Arch Neurol. 2001; 58(2):225-30. DOI: 10.1001/archneur.58.2.225. View

19.

Ellis T, Atkinson M . The clinical significance of an autoimmune response against glutamic acid decarboxylase. Nat Med. 1996; 2(2):148-53. DOI: 10.1038/nm0296-148. View

20.

Liguori R, Cordivari C, Lugaresi E, Montagna P . Botulinum toxin A improves muscle spasms and rigidity in stiff-person syndrome. Mov Disord. 1997; 12(6):1060-3. DOI: 10.1002/mds.870120636. View