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Chapter 14 - Autoimmunity Against the Inhibitory Synapsis

from Section 3 - Specific Syndromes and Diseases

Published online by Cambridge University Press:  27 January 2022

Josep Dalmau  and
Francesc Graus
Josep Dalmau
Affiliation:
Universitat de Barcelona
Francesc Graus
Affiliation:
Universitat de Barcelona
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Summary

This chapter focuses on the syndromes that are associated with antibodies that target proteins of the inhibitory synapses. Two antibodies are directed against intracellular presynaptic proteins, including glutamic acid decarboxylase (GAD), a key enzyme in the synthesis of GABA, and amphiphysin, which is involved in the presynaptic reuptake of neurotransmitters. Both antibodies are associated with stiff-person syndrome (SPS), which results in rigidity in proximal muscles of legs, abdomen, and lower back, impaired gait, muscles spasms, exaggerated startle responses to acoustic or tactile stimuli, and anxiety and task-specific phobias. Three antibodies are directed against cell surface receptors, including GABAaR and GABAbR, and the glycine receptor (GlyR). Encephalitis with prominent seizures is the common presentation of patients with antibodies against GABAaR or GABAbR, whereas antibodies against GlyR associate with an SPS variant named progressive encephalomyelitis with rigidity and myoclonus (PERM). In addition, this chapter includes the antibodies against dipeptidyl-peptidase-like protein 6 (DPPX), an auxiliary subunit of the Kv4.2 potassium channels that is not restricted to inhibitory synapses, but patients with this disorder frequently show CNS hyperexcitability and sometimes clinical features similar to PERM.

Keywords

Stiff-person syndromeprogressive encephalomyelitis with rigidity and myoclonus (PERM)paraneoplastic neurological syndromesGAD antibodiesglycine receptor antibodiesamphiphysin antibodiesanti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis
Type
Chapter
Information
Autoimmune Encephalitis and Related Disorders of the Nervous System , pp. 391 - 410
Publisher: Cambridge University Press
Print publication year: 2022

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References

Dalmau, J, Geis, C, Graus, F. Autoantibodies to synaptic receptors and neuronal cell surface proteins in autoimmune diseases of the central nervous system. Physiol Rev 2017;97:839–887.Google Scholar
Pelkey, KA, Chittajallu, R, Craig, MT, et al. Hippocampal GABAergic inhibitory interneurons. Physiol Rev 2017;97:1619–1747.Google Scholar
Moore, LA, Trussell, LO. Corelease of inhibitory neurotransmitters in the mouse auditory midbrain. J Neurosci 2017;37:9453–9464.Google Scholar
Wojcik, SM, Katsurabayashi, S, Guillemin, I, et al. A shared vesicular carrier allows synaptic corelease of GABA and glycine. Neuron 2006;50:575–587.CrossRefGoogle ScholarPubMed
Hirose, S. Mutant GABA(A) receptor subunits in genetic (idiopathic) epilepsy. Progr Brain Res 2014;213:55–85.Google Scholar
Dreissen, YE, Tijssen, MA. The startle syndromes: physiology and treatment. Epilepsia 2012;53(Suppl 7):3–11.Google Scholar
Warich-Kirches, M, Von Bossanyi, P, Treuheit, T, et al. Stiff-man syndrome: possible autoimmune etiology targeted against GABA-ergic cells. Clin Neuropathol 1997;16:214–219.Google Scholar
De Felipe, J, Marco, P, Fairen, A, Jones, EG. Inhibitory synaptogenesis in mouse somatosensory cortex. Cereb Cortex 1997;7:619–634.Google Scholar
Betz, H, Langosch, D, Hoch, W, et al. Structure and expression of inhibitory glycine receptors. Adv Exp Med Biol 1991;287:421–429.Google Scholar
Jacob, TC, Moss, SJ, Jurd, R. GABA(A) receptor trafficking and its role in the dynamic modulation of neuronal inhibition. Nat Rev Neurosci 2008;9:331–343.CrossRefGoogle ScholarPubMed
Tamas, G, Lorincz, A, Simon, A, Szabadics, J. Identified sources and targets of slow inhibition in the neocortex. Science 2003;299:1902–1905.Google Scholar
Butler, MH, Hayashi, A, Ohkoshi, N, et al. Autoimmunity to gephyrin in stiff-man syndrome. Neuron 2000;26:307–312.Google Scholar
Kasaragod, VB, Schindelin, H. Structure–function relationships of glycine and GABAA receptors and their interplay with the scaffolding protein gephyrin. Front Molec Neurosci 2018;11:317.Google Scholar
Spatola, M, Petit-Pedrol, M, Simabukuro, MM, et al. Investigations in GABAA receptor antibody-associated encephalitis. Neurology 2017;88:1012–1020.Google Scholar
Bode, A, Lynch, JW. The impact of human hyperekplexia mutations on glycine receptor structure and function. Molec Brain 2014;7:2.Google Scholar
Schaefer, N, Roemer, V, Janzen, D, Villmann, C. Impaired glycine receptor trafficking in neurological diseases. Front Molec Neurosci 2018;11:291.Google Scholar
Macdonald, RL, Kang, JQ, Gallagher, MJ. Mutations in GABAA receptor subunits associated with genetic epilepsies. J Physiol 2010;588:1861–1869.Google Scholar
Pruss, H, Kirmse, K. Pathogenic role of autoantibodies against inhibitory synapses. Brain Res 2018;1701:146–152.CrossRefGoogle ScholarPubMed
Erlander, MG, Tobin, AJ. The structural and functional heterogeneity of glutamic acid decarboxylase: a review. Neurochem Research 1991;16:215–226.Google Scholar
Werner, C, Pauli, M, Doose, S, et al. Human autoantibodies to amphiphysin induce defective presynaptic vesicle dynamics and composition. Brain 2016;139:365–379.CrossRefGoogle ScholarPubMed
McKeon, A, Robinson, MT, McEvoy, KM, et al. Stiff-man syndrome and variants: clinical course, treatments, and outcomes. Arch Neurol 2012;69:230–238.Google Scholar
Hoftberger, R, Titulaer, MJ, Sabater, L, et al. Encephalitis and GABAB receptor antibodies: novel findings in a new case series of 20 patients. Neurology 2013;81:1500–1506.Google Scholar
Carvajal-Gonzalez, A, Leite, MI, Waters, P, et al. Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes. Brain 2014;137:2178–2192.CrossRefGoogle ScholarPubMed
Piepgras, J, Holtje, M, Michel, K, et al. Anti-DPPX encephalitis: pathogenic effects of antibodies on gut and brain neurons. Neurology 2015;85:890–897.CrossRefGoogle ScholarPubMed
Balint, B, Jarius, S, Nagel, S, et al. Progressive encephalomyelitis with rigidity and myoclonus: a new variant with DPPX antibodies. Neurology 2014;82:1521–1528.Google Scholar
Gresa-Arribas, N, Arino, H, Martinez-Hernandez, E, et al. Antibodies to inhibitory synaptic proteins in neurological syndromes associated with glutamic acid decarboxylase autoimmunity. PLoS One 2015;10:e0121364.Google Scholar
Ariño, H, Hoftberger, R, Gresa-Arribas, N, et al. Paraneoplastic neurological syndromes and glutamic acid decarboxylase antibodies. JAMA Neurol 2015;72:874–881.CrossRefGoogle ScholarPubMed
Pittock, SJ, Lucchinetti, CF, Parisi, JE, et al. Amphiphysin autoimmunity: paraneoplastic accompaniments. Ann Neurol 2005;58:96–107.Google Scholar
Moersch, F, Woltman, H. Progressive fluctuating muscular rigidity and spasm (‘stiffman syndrome’): report of a case and some observations in 13 other cases. Mayo Clin Proc 1956;31:421–427.Google Scholar
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;318:1012–1020.CrossRefGoogle Scholar
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;322:1555–1560.Google Scholar
Levy, LM, Dalakas, MC, Floeter, MK. The stiff-person syndrome: an autoimmune disorder affecting neurotransmission of gamma-aminobutyric acid. Ann Intern Med 1999;131:522–530.Google Scholar
Martinez-Hernandez, E, Arino, H, McKeon, A, et al. Clinical and immunological investigations in 121 patients with stiff-person spectrum disorder. JAMA Neurol 2016;73:714–720.CrossRefGoogle Scholar
Saiz, A, Graus, F, Valldeoriola, F, Valls-Sole, J, Tolosa, E. Stiff-leg syndrome: a focal form of stiff-man syndrome. Ann Neurol 1998;43:400–403.CrossRefGoogle ScholarPubMed
Brown, P, Rothwell, JC, Marsden, CD. The stiff leg syndrome. J Neurol Neurosurg Psychiatry 1997;62:31–37.Google Scholar
Leigh, PN, Rothwell, JC, Traub, M, Marsden, CD. A patient with reflex myoclonus and muscle rigidity: ‘jerking stiff-man syndrome’. J Neurol Neurosurg Psychiatry 1980;43:1125–1131.Google Scholar
Meinck, HM, Thompson, PD. Stiff man syndrome and related conditions. Mov Disord 2002;17:853–866.CrossRefGoogle ScholarPubMed
Rakocevic, G, Alexopoulos, H, Dalakas, MC. Quantitative clinical and autoimmune assessments in stiff person syndrome: evidence for a progressive disorder. BMC Neurol 2019;19:1.Google Scholar
Henningsen, P, Meinck, HM. Specific phobia is a frequent non-motor feature in stiff man syndrome. J Neurol Neurosurg Psychiatry 2003;74:462–465.Google Scholar
Ameli, R, Snow, J, Rakocevic, G, Dalakas, MC. A neuropsychological assessment of phobias in patients with stiff person syndrome. Neurology 2005;64:1961–1963.Google Scholar
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;65:633–640.Google Scholar
Saiz, A, Blanco, Y, Sabater, L, et al. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain 2008;131:2553–2563.Google Scholar
Maddison, P, Mills, KR, Newsom-Davis, J. Clinical electrophysiological characterization of the acquired neuromyotonia phenotype of autoimmune peripheral nerve hyperexcitability. Muscle Nerve 2006;33:801–808.CrossRefGoogle ScholarPubMed
Mamoli, B, Heiss, WD, Maida, E, Podreka, I. Electrophysiological studies on the ‘stiff-man’ syndrome. J Neurol 1977;217:111–121.Google Scholar
Espay, AJ, Chen, R. Rigidity and spasms from autoimmune encephalomyelopathies: stiff-person syndrome. Muscle Nerve 2006;34:677–690.Google Scholar
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;51:85–93.Google Scholar
Meinck, HM, Kuster, S, Benecke, R, Conrad, B. The flexor reflex–influence of stimulus parameters on the reflex response. Electroencephalogr Clin Neurophysiol 1985;61:287–298.Google Scholar
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;47:280–287.Google Scholar
Sandbrink, F, Syed, NA, Fujii, MD, Dalakas, MC, Floeter, MK. Motor cortex excitability in stiff-person syndrome. Brain 2000;123:2231–2239.Google Scholar
Koerner, C, Wieland, B, Richter, W, Meinck, HM. Stiff-person syndromes: motor cortex hyperexcitability correlates with anti-GAD autoimmunity. Neurology 2004;62:1357–1362.Google Scholar
Dalakas, MC, Li, M, Fujii, M, Jacobowitz, DM. Stiff person syndrome: quantification, specificity, and intrathecal synthesis of GAD65 antibodies. Neurology 2001;57:780–784.Google Scholar
Ellis, TM, Atkinson, MA. The clinical significance of an autoimmune response against glutamic acid decarboxylase. Nat Med 1996;2:148–153.Google Scholar
Saiz, A, Arpa, J, Sagasta, A, et al. Autoantibodies to glutamic acid decarboxylase in three patients with cerebellar ataxia, late-onset insulin-dependent diabetes mellitus, and polyendocrine autoimmunity. Neurology 1997;49:1026–1030.Google Scholar
Meinck, HM, Faber, L, Morgenthaler, N, et al. Antibodies against glutamic acid decarboxylase: prevalence in neurological diseases. J Neurol Neurosurg Psychiatry 2001;71:100–103.Google Scholar
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 1 diabetes mellitus. Mayo Clin Proc 1998;73:1161–1166.CrossRefGoogle Scholar
Schmidli, RS, Colman, PG, Bonifacio, E. Disease sensitivity and specificity of 52 assays for glutamic acid decarboxylase antibodies: the Second International GADAB Workshop. Diabetes 1995;44:636–640.Google Scholar
Graus, F, Saiz, A, Dalmau, J. GAD antibodies in neurological disorders: insights and challenges. Nat Rev Neurol 2020;16:353–365.Google Scholar
McKeon, A, Martinez-Hernandez, E, Lancaster, E, et al. Glycine receptor autoimmune spectrum with stiff-man syndrome phenotype. JAMA Neurol 2013;70:44–50.CrossRefGoogle ScholarPubMed
Brown, P, Marsden, CD. The stiff man and stiff man plus syndromes. J Neurol 1999;246:648–652.Google Scholar
Lorish, TR, Thorsteinsson, G, Howard, FM Jr. Stiff-man syndrome updated. Mayo Clin Proc 1989;64:629–636.Google Scholar
Wu, Y, Matsui, H, Tomizawa, K. Amphiphysin I and regulation of synaptic vesicle endocytosis. Acta medica Okayama 2009;63:305–323.Google Scholar
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;328:546–551.Google Scholar
De Camilli, P, Thomas, A, Cofiell, R, et al. The synaptic vesicle-associated protein amphiphysin is the 128-kD autoantigen of stiff-man syndrome with breast cancer. J Exp Med 1993;178:2219–2223.Google Scholar
Murinson, BB, Guarnaccia, JB. Stiff-person syndrome with amphiphysin antibodies: distinctive features of a rare disease. Neurology 2008;71:1955–1958.Google Scholar
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;66:214–217.Google Scholar
Nguyen-Huu, BK, Urban, PP, Schreckenberger, M, Dieterich, M, Werhahn, KJ. Antiamphiphysin-positive stiff-person syndrome associated with small cell lung cancer. Mov Disord 2006;21:1285–1287.Google Scholar
Dubey, D, Jitprapaikulsan, J, Bi, H, et al. Amphiphysin-IgG autoimmune neuropathy: a recognizable clinicopathologic syndrome. Neurology 2019;93:e1873–e1880.Google Scholar
Hagiwara, H, Enomoto-Nakatani, S, Sakai, K, et al. Stiff-person syndrome associated with invasive thymoma: a case report. J Neurol Sci 2001;193:59–62.CrossRefGoogle ScholarPubMed
Thomas, S, Critchley, P, Lawden, M, et al. Stiff person syndrome with eye movement abnormality, myasthenia gravis, and thymoma. J Neurol Neurosurg Psychiatry 2005;76:141–142.Google Scholar
Tanaka, H, Matsumura, A, Okumura, M, et al. Stiff man syndrome with thymoma. Ann Thorac Surg 2005;80:739–741.Google Scholar
Iwata, T, Inoue, K, Mizuguchi, S, et al. Thymectomy for paraneoplastic stiff-person syndrome associated with invasive thymoma. J Thorac Cardiovasc Surg 2006;132:196–197.Google Scholar
Kobayashi, R, Kaji, M, Horiuchi, S, et al. Recurrent thymoma with stiff-person syndrome and pure red blood cell aplasia. Ann Thorac Surg 2014;97:1802–1804.Google Scholar
Aghajanzadeh, M, Alavi, A, Aghajanzadeh, G, Massahania, S. Stiff man syndrome with invasive thymic carcinoma. Arch Iran Med 2013;16:195–196.Google Scholar
Agarwal, PA, Ichaporia, NR. Glutamic acid decarboxylase antibody-positive paraneoplastic stiff limb syndrome associated with carcinoma of the breast. Neurol India 2010;58:449–451.Google Scholar
Silverman, IE. Paraneoplastic stiff limb syndrome. J Neurol Neurosurg Psychiatry 1999;67:126–127.Google Scholar
Sinnreich, M, Assal, F, Hefft, S, et al. Anti-GAD antibodies and breast cancer in a patient with stiff-person syndrome: a puzzling association. Eur Neurol 2001;46:51–52.Google Scholar
Schiff, D, Dalmau, J, Myers, DJ. Anti-GAD antibody positive stiff-limb syndrome in multiple myeloma. J Neurooncol 2003;65:173–175.Google Scholar
McHugh, JC, Murray, B, Renganathan, R, Connolly, S, Lynch, T. GAD antibody positive paraneoplastic stiff person syndrome in a patient with renal cell carcinoma. Mov Disord 2007;22:1343–1346.Google Scholar
Ferrari, P, Federico, M, Grimaldi, LM, Silingardi, V. Stiff-man syndrome in a patient with Hodgkin’s disease: an unusual paraneoplastic syndrome. Haematologica 1990;75:570–572.Google Scholar
Rakocevic, G, Hussain, A. Stiff person syndrome improvement with chemotherapy in a patient with cutaneous T cell lymphoma. Muscle Nerve 2013;47:938–939.Google Scholar
Koca, I, Ucar, M, Kalender, ME, Alkan, S. The horses are the first thought but one must not forget the zebras even if they are rare: stiff person syndrome associated with malignant mesothelioma. BMJ Case Rep 2014;2014:bcr2013203455.CrossRefGoogle Scholar
Sarwari, N, Galili, Y, Perez, A, Avgeropoulos, N, Tseng, J. Unusual presentation of lung adenocarcinoma with paraneoplastic stiff person syndrome: role of EGFR tyrosine kinase inhibitors. J Thorac Oncol 2019;14:e179–e180.Google Scholar
Yong, SYS, Teo, JY, Yong, KP, Goh, BKP. Paraneoplastic stiff person syndrome secondary to pancreatic adenocarcinoma. J Gastrointest Surg 2018;22:172–174.Google Scholar
Levy, LM, Levy-Reis, I, Fujii, M, Dalakas, MC. Brain gamma-aminobutyric acid changes in stiff-person syndrome. Arch Neurol 2005;62:970–974.Google Scholar
Alexopoulos, H, Dalakas, MC. Immunology of stiff person syndrome and other GAD-associated neurological disorders. Exp Rev Clin Immunol 2013;9:1043–1053.Google Scholar
Bu, DF, Erlander, MG, Hitz, BC, et al. Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene. Proc Natl Acad Sci USA 1992;89:2115–2119.Google Scholar
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;44:194–201.Google Scholar
Chang, T, Alexopoulos, H, McMenamin, M, et al. Neuronal surface and glutamic acid decarboxylase autoantibodies in nonparaneoplastic stiff person syndrome. JAMA Neurol 2013;70:1140–1149.Google Scholar
Chang, T, Alexopoulos, H, Pettingill, P, et al. Immunization against GAD induces antibody binding to GAD-independent antigens and brainstem GABAergic neuronal loss. PLoS One 2013;8:e72921.Google Scholar
Nemni, R, Caniatti, LM, Gironi, M, Bazzigaluppi, E, De Grandis, D. Stiff person syndrome does not always occur with maternal passive transfer of GAD65 antibodies. Neurology 2004;62:2101–2102.Google Scholar
Bjork, E, Velloso, LA, Kampe, O, Karlsson, FA. GAD autoantibodies in IDDM, stiff-man syndrome, and autoimmune polyendocrine syndrome type I recognize different epitopes. Diabetes 1994;43:161–165.Google Scholar
Raju, R, Foote, J, Banga, JP, et al. Analysis of GAD65 autoantibodies in stiff-person syndrome patients. J Immunol 2005;175:7755–7762.Google Scholar
Fouka, P, Alexopoulos, H, Akrivou, S, et al. GAD65 epitope mapping and search for novel autoantibodies in GAD-associated neurological disorders. J Neuroimmunol 2015;281:73–77.Google Scholar
Manto, MU, Laute, MA, Aguera, M, et al. Effects of anti-glutamic acid decarboxylase antibodies associated with neurological diseases. Ann Neurol 2007;61:544–551.CrossRefGoogle ScholarPubMed
Geis, C, Weishaupt, A, Grunewald, B, et al. Human stiff-person syndrome IgG induces anxious behavior in rats. PLoS One 2011;6:e16775.Google Scholar
Hansen, N, Grunewald, B, Weishaupt, A, et al. Human stiff person syndrome IgG-containing high-titer anti-GAD65 autoantibodies induce motor dysfunction in rats. Exp Neurol 2013;239:202–209.Google Scholar
Manto, M, Honnorat, J, Hampe, CS, et al. Disease-specific monoclonal antibodies targeting glutamate decarboxylase impair GABAergic neurotransmission and affect motor learning and behavioral functions. Front Behav Neurosci 2015;9:78.Google Scholar
Sommer, C, Weishaupt, A, Brinkhoff, J, et al. Paraneoplastic stiff-person syndrome: passive transfer to rats by means of IgG antibodies to amphiphysin. Lancet 2005;365:1406–1411.Google Scholar
Geis, C, Weishaupt, A, Hallermann, S, et al. Stiff person syndrome-associated autoantibodies to amphiphysin mediate reduced GABAergic inhibition. Brain 2010;133:3166–3180.Google Scholar
Balint, B, Meinck, HM. Pragmatic treatment of stiff person spectrum disorders. Mov Disord Clin Pract 2018;5:394–401.Google Scholar
Miller, F, Korsvik, H. Baclofen in the treatment of stiff-man syndrome. Ann Neurol 1981;9:511–512.Google Scholar
Sechi, G, Barrocu, M, Piluzza, MG, et al. Levetiracetam in stiff-person syndrome. J Neurol 2008;255:1721–1725.Google Scholar
Squintani, G, Bovi, T, Ferigo, L, et al. Efficacy of pregabalin in a case of stiff-person syndrome: clinical and neurophysiological evidence. J Neurol Sci 2012;314:166–168.Google Scholar
Meinck, HM, Conrad, B. Neuropharmacological investigations in the stiff-man syndrome. J Neurol 1986;233:340–347.Google Scholar
Murinson, BB, Rizzo, M. Improvement of stiff-person syndrome with tiagabine. Neurology 2001;57:366.Google Scholar
Spehlmann, R, Norcross, K, Rasmus, SC, Schlageter, NL. Improvement of stiff-man syndrome with sodium valproate. Neurology 1981;31:1162–1163.Google Scholar
Seitz, RJ, Blank, B, Kiwit, JC, Benecke, R. Stiff-person syndrome with anti-glutamic acid decarboxylase autoantibodies: complete remission of symptoms after intrathecal baclofen administration. J Neurol 1995;242:618–622.Google Scholar
Newton, JC, Harned, ME, Sloan, PA, Salles, SS. Trialing of intrathecal baclofen therapy for refractory stiff-person syndrome. Reg Anesth Pain Med 2013;38:248–250.Google Scholar
Maramattom, BV. Intrathecal baclofen pump implantation in a case of stiff person syndrome. Neurol India 2010;58:115–117.Google Scholar
Ho, BL, Shih, PY. Successful intrathecal baclofen therapy for seronegative stiff-person syndrome: a case report. Acta Neurologica Taiwanica 2008;17:172–176.Google Scholar
Silbert, PL, Matsumoto, JY, McManis, PG, et al. Intrathecal baclofen therapy in stiff-man syndrome: a double-blind, placebo-controlled trial. Neurology 1995;45:1893–1897.Google Scholar
Stayer, C, Tronnier, V, Dressnandt, J, et al. Intrathecal baclofen therapy for stiff-man syndrome and progressive encephalomyelopathy with rigidity and myoclonus. Neurology 1997;49:1591–1597.Google Scholar
Abbatemarco, JR, Willis, MA, Wilson, RG, et al. Case series: intrathecal baclofen therapy in stiff-person syndrome. Neuromodulation 2018;21:655–659.Google Scholar
Liguori, R, Cordivari, C, Lugaresi, E, Montagna, P. Botulinum toxin A improves muscle spasms and rigidity in stiff-person syndrome. Mov Disord 1997;12:1060–1063.Google Scholar
Davis, D, Jabbari, B. Significant improvement of stiff-person syndrome after paraspinal injection of botulinum toxin A. Mov Disord 1993;8:371–373.Google Scholar
Anagnostou, E, Zambelis, T. Botulinum toxin A in anti-GAD-positive stiff-limb syndrome. Muscle Nerve 2012;46:457–458.Google Scholar
Dalakas, MC, Fujii, M, Li, M, et al. High-dose intravenous immune globulin for stiff-person syndrome. N Engl J Med 2001;345:1870–1876.Google Scholar
Pagano, MB, Murinson, BB, Tobian, AA, King, KE. Efficacy of therapeutic plasma exchange for treatment of stiff-person syndrome. Transfusion 2014;54:1851–1856.Google Scholar
McKeon, A, Tracy, JA. GAD65 neurological autoimmunity. Muscle Nerve 2017;56:15–27.CrossRefGoogle ScholarPubMed
Baizabal-Carvallo, JF, Jankovic, J. Stiff-person syndrome: insights into a complex autoimmune disorder. J Neurol Neurosurg Psychiatry 2015;86:840–848.Google Scholar
Fekete, R, Jankovic, J. Childhood stiff-person syndrome improved with rituximab. Case Rep Neurol 2012;4:92–96.Google Scholar
Bacorro, EA, Tehrani, R. Stiff-person syndrome: persistent elevation of glutamic acid decarboxylase antibodies despite successful treatment with rituximab. J Clin Rheumatol 2010;16:237–239.Google Scholar
Qureshi, A, Hennessy, M. Stiff person syndrome (SPS) complicated by respiratory failure: successful treatment with rituximab. J Neurol 2012;259:180–181.Google Scholar
Lobo, ME, Araujo, ML, Tomaz, CA, Allam, N. Stiff-person syndrome treated with rituximab. BMJ Case Rep 2010;2010:bcr0520103021.Google Scholar
Baker, MR, Das, M, Isaacs, J, Fawcett, PR, Bates, D. Treatment of stiff person syndrome with rituximab. J Neurol Neurosurg Psychiatry 2005;76:999–1001.Google Scholar
Dalakas, MC, Rakocevic, G, Dambrosia, JM, Alexopoulos, H, McElroy, B. A double-blind, placebo-controlled study of rituximab in patients with stiff person syndrome. Ann Neurol 2017;82:271–277.Google Scholar
Sharrack, B, Saccardi, R, Alexander, T, et al. Autologous haematopoietic stem cell transplantation and other cellular therapy in multiple sclerosis and immune-mediated neurological diseases: updated guidelines and recommendations from the EBMT Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE). Bone Marrow Transplant 2020;55:283–306.Google Scholar
Sanders, S, Bredeson, C, Pringle, CE, et al. Autologous stem cell transplantation for stiff person syndrome: two cases from the Ottawa blood and marrow transplant program. JAMA Neurol 2014;71:1296–1299.Google Scholar
Kass-Iliyya, L, Snowden, JA, Thorpe, A, et al. Autologous haematopoietic stem cell transplantation for refractory stiff-person syndrome: the UK experience. J Neurol 2021;268:265–275.Google Scholar
Burt, RK, Balabanov, R, Han, X, et al. Autologous hematopoietic stem cell transplantation for Stiff Person Spectrum Disorder: a clinical trial. Neurology 2020;96:e817–e830.Google Scholar
Whiteley, AM, Swash, M, Urich, H. Progressive encephalomyelitis with rigidity. Brain 1976;99:27–42.Google Scholar
Campbell, AM, Garland, H. Subacute myoclonic spinal neuronitis. J Neurol Neurosurg Psychiatry 1956;19:268–274.Google Scholar
Kasperek, S, Zebrowski, S. Stiff-man syndrome and encephalomyelitis: report of a case. Arch Neurol 1971;24:22–30.Google Scholar
Lhermitte, F, Chain, F, Escourolle, R, et al. [A further case of tetanus-like contracture distinct from the stiff man syndrome. Pharmacological and neuropathological study of a case of predominantly spinal encephalomyelitis]. Revue neurologique 1973;128:3–21.Google Scholar
Howell, DA, Lees, AJ, Toghill, PJ. Spinal internuncial neurones in progressive encephalomyelitis with rigidity. J Neurol Neurosurg Psychiatry 1979;42:773–785.Google Scholar
Hutchinson, M, Waters, P, McHugh, J, et al. Progressive encephalomyelitis, rigidity, and myoclonus: a novel glycine receptor antibody. Neurology 2008;71:1291–1292.Google Scholar
Shugaiv, E, Leite, MI, Sehitoglu, E, et al. Progressive encephalomyelitis with rigidity and myoclonus: a syndrome with diverse clinical features and antibody responses. Eur Neurol 2013;69:257–262.Google Scholar
Kyskan, R, Chapman, K, Mattman, A, Sin, D. Antiglycine receptor antibody and encephalomyelitis with rigidity and myoclonus (PERM) related to small cell lung cancer. BMJ Case Rep 2013;2013:bcr2013010027.Google Scholar
Spitz, M, Ferraz, HB, Barsottini, OG, Gabbai, AA. Progressive encephalomyelitis with rigidity: a paraneoplastic presentation of oat cell carcinoma of the lung: case report. Arq Neuropsiquiatr 2004;62:547–549.Google Scholar
Mas, N, Saiz, A, Leite, MI, et al. Antiglycine-receptor encephalomyelitis with rigidity. J Neurol Neurosurg Psychiatry 2011;82:1399–1401.Google Scholar
Peeters, E, Vanacker, P, Woodhall, M, et al. Supranuclear gaze palsy in glycine receptor antibody-positive progressive encephalomyelitis with rigidity and myoclonus. Mov Disord 2012;27:1830–1832.Google Scholar
Bourke, D, Roxburgh, R, Vincent, A, et al. Hypoventilation in glycine-receptor antibody related progressive encephalomyelitis, rigidity and myoclonus. J Clin Neurosci 2014;21:876–878.Google Scholar
Stern, WM, Howard, R, Chalmers, RM, et al. Glycine receptor antibody mediated Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM): a rare but treatable neurological syndrome. Pract Neurol 2014;14:123–127.Google Scholar
Piotrowicz, A, Thumen, A, Leite, MI, Vincent, A, Moser, A. A case of glycine-receptor antibody-associated encephalomyelitis with rigidity and myoclonus (PERM): clinical course, treatment and CSF findings. J Neurol 2011;258:2268–2270.CrossRefGoogle ScholarPubMed
Jungehulsing, GJ, Behse, F, Grosse, P. Can progressive encephalomyelitis with rigidity mimic motor neuron disease? Case report and review of the literature. J Neurol 2005;252:863–865.Google Scholar
Kenda, J, Svigelj, V, Rodi, Z, et al. Glycine receptor antibodies and progressive encephalomyelitis with rigidity and myoclonus with predominant motor neuron degeneration: expanding the clinical spectrum. J Neurol Sci 2015;353:177–178.Google Scholar
Hinson, SR, Lopez-Chiriboga, AS, Bower, JH, et al. Glycine receptor modulating antibody predicting treatable stiff-person spectrum disorders. Neurol Neuroimmunol Neuroinflamm 2018;5:e438.Google Scholar
Crisp, SJ, Balint, B, Vincent, A. Redefining progressive encephalomyelitis with rigidity and myoclonus after the discovery of antibodies to glycine receptors. Curr Opin Neurol 2017;30:310–316.Google Scholar
Piquet, AL, Khan, M, Warner, JEA, et al. Novel clinical features of glycine receptor antibody syndrome: a series of 17 cases. Neurol Neuroimmunol Neuroinflamm 2019;6:e592.Google Scholar
Casado, JL, Gil-Peralta, A, Graus, F, et al. Anti-Ri antibodies associated with opsoclonus and progressive encephalomyelitis with rigidity. Neurology 1994;44:1521–1522.Google Scholar
Ishii, A, Hayashi, A, Ohkoshi, N, Matsuno, S, Shoji, S. Progressive encephalomyelitis with rigidity associated with anti-amphiphysin antibodies. J Neurol Neurosurg Psychiatry 2004;75:661–662.Google Scholar
Hara, M, Ariño, H, Petit-Pedrol, M, et al. DPPX-antibody associated encephalitis: main syndrome and antibody effects. Neurology 2017;88:1340–1348.Google Scholar
Rauschenberger, V, von Wardenburg, N, Schaefer, N, et al. Glycine receptor autoantibodies impair receptor function and induce motor dysfunction. Ann Neurol 2020;88:544–561.Google Scholar
Crisp, SJ, Dixon, CL, Jacobson, L, et al. Glycine receptor autoantibodies disrupt inhibitory neurotransmission. Brain 2019;142:3398–3410.Google Scholar
Ozaki, K, Ohkubo, T, Yamada, T, et al. Progressive encephalomyelitis with rigidity and myoclonus resolving after thymectomy with subsequent anasarca: an autopsy case. Intern Med (Tokyo, Japan) 2018;57:3451–3458.Google Scholar
Turner, MR, Irani, SR, Leite, MI, et al. Progressive encephalomyelitis with rigidity and myoclonus: glycine and NMDA receptor antibodies. Neurology 2011;77:439–443.Google Scholar
Swayne, A, Tjoa, L, Broadley, S, et al. Antiglycine receptor antibody related disease: a case series and literature review. Eur J Neurol 2018;25:1290–1298.Google Scholar
Boronat, A, Gelfand, JM, Gresa-Arribas, N, et al. Encephalitis and antibodies to dipeptidyl-peptidase-like protein-6, a subunit of Kv4.2 potassium channels. Ann Neurol 2013;73:120–128.Google Scholar
Hara, M, Arino, H, Petit-Pedrol, M, et al. DPPX antibody-associated encephalitis: main syndrome and antibody effects. Neurology 2017;88:1340–1348.Google Scholar
Tobin, WO, Lennon, VA, Komorowski, L, et al. DPPX potassium channel antibody: frequency, clinical accompaniments, and outcomes in 20 patients. Neurology 2014;83:1797–1803.Google Scholar
Doherty, L, Gold, D, Solnes, L, Probasco, J, Venkatesan, A. Anti-DPPX encephalitis: prominent nystagmus reflected by extraocular muscle FDG-PET avidity. Neurol Neuroimmunol Neuroinflamm 2017;4:e361.Google Scholar
Stokin, GB, Popovic, M, Gelpi, E, et al. Neuropathologic features of anti-dipeptidyl-peptidase-like protein-6 antibody encephalitis. Neurology 2015;84:430–432.Google Scholar
Dougherty, K, Covarrubias, M. A dipeptidyl aminopeptidase-like protein remodels gating charge dynamics in Kv4.2 channels. J Gen Physiol 2006;128:745–753.Google Scholar
Ohkawa, T, Fukata, Y, Yamasaki, M, et al. Autoantibodies to epilepsy-related LGI1 in limbic encephalitis neutralize LGI1-ADAM22 interaction and reduce synaptic AMPA receptors. J Neurosci 2013;33:18161–18174.Google Scholar
Petit-Pedrol, M, Sell, J, Planaguma, J, et al. LGI1 antibodies alter Kv1.1 and AMPA receptors changing synaptic excitability, plasticity and memory. Brain 2018;141:3144–3159.Google Scholar
Huijbers, MG, Querol, LA, Niks, EH, et al. The expanding field of IgG4-mediated neurological autoimmune disorders. Eur J Neurol 2015;22:1151–1161.Google Scholar

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