Antikörper-Diagnostik bei Verdacht auf autoimmune Hirnentzündungen

Zusammenfassung

Der Nachweis spezifischer gegen Hirngewebe gerichteter Autoantikörper hat zu einer rasanten Weiterentwicklung in der Neurologie und Pädiatrie geführt. Mit ihrer Hilfe können heute bestimmte Symptome zweifelsfrei zugeordnet werden, diagnostische Pfade werden vereinfacht und immunmodulierende Therapien können gezielter eingesetzt werden. Die Krankheitsbilder reichen von Enzephalitiden und Epilepsien bis zu demyelinisierenden Erkrankungen, Psychosen und Demenzen. Angesichts der vielen neuen zugrundeliegenden Autoantikörper gegen Ionen -kanäle und Rezeptoren auf Nervenzellen (zum Beispiel NMDA-, AMPA- und GABA Rezeptoren, LGI1, DPPX) wächst die Schwierigkeit, den Überblick über das variable Erkrankungsspektrum zu behalten. Neben klinischer Untersuchung und MRT-Bild -gebung stehen die Lumbalpunktion und die Bestimmung der Antikörper mit zellbasierten Testverfahren im Vordergrund differenzial -dia gnostischer Entscheidungen und rascher Therapie. Der Nachweis immer neuer Antikörper wird sich in den kommenden Jahren fort-setzen und zu einem besseren Verständnis der Pathomechanismen auch einiger neurologischer Krankheiten führen, die bisher als unheilbar oder psychosomatisch galten.

Summary

Identification of specific auto-antibodies against brain tissue resulted in profound changes in clinical neurology and pediatrics. Antibody detection now allows definite conclusions about the underlying disease mechanisms, streamlines diagnostic pathways, and accelerates initiation of immunotherapy. The disease spectrum is variable and ranges from encephalitis and epilepsy to demyelinating disorders, psychosis, and dementia. Most antibodies target neuronal surface proteins, in particular ion channels and receptors, such as NMDA, AMPA, or GABA receptors, LGI1, and DPPX. Together with clinical examination and MR imaging, cerebrospinal fluid analysis and detection of neuronal surface antibodies in cell-based assays have become the diagnostic mainstay, guiding differential diagnoses and rapid therapy. Further pathogenic auto-antibodies will be detected in future years, thus helping to better understand disease mechanisms even in some of those neurological disorders that until now had to be considered incurable or psychosomatic.

Schlüsselwörter

Enzephalitis - NMDA-Rezeptor - Autoantikörper

Keywords

Encephalitis - NMDA receptor - auto-antibodies

• Literatur

• 1 Adang LA, Lynch DR, Panzer JA. Pediatric anti-NMDA receptor encephalitis is seasonal. Ann Clin Transl Neurol 2014; 1: 921-925.
• 2 Armangue T, Leypoldt F, Malaga I. et al. Herpes Simplex Virus Encephalitis is a Trigger of Brain Autoimmunity. Ann Neurol 2013 Dec 8
• 3 Armangue T, Titulaer MJ, Malaga I. et al Pediatric Anti-N-methyl-D-Aspartate Receptor Encephalitis-Clinical Analysis and Novel Findings in a Series of 20 Patients. J Pediatr 2013; 162: 850-856.
• 4 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.
• 5 Bataller L, Galiano R, Garcia-Escrig M. et al Reversible paraneoplastic limbic encephalitis associated with antibodies to the AMPA receptor. Neurology 2010; 74: 265-267.
• 6 Borisow N, Pruss H, Paul F. [Therapeutic options for autoimmune encephalomyelitis]. Nervenarzt 2013; 84: 461-465.
• 7 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.
• 8 Dale R, Irani SR, Brilot F. N-Methyl-D-Aspartate Receptor Antibodies in Pediatric Dyskinetic Encephalitis Lethargica. Ann Neurol 2009; 66: 704-709.
• 9 Dalmau J, Gleichman AJ, Hughes EG. et al Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008; 7: 1091-1098.
• 10 Doss S, Wandinger KP, Hyman BT. et al High prevalence of NMDA receptor IgA/IgM antibodies in different dementia types. Ann Clin Transl Neurol 2014; 1: 822-832.
• 11 Finke C, Kopp UA, Scheel M. et al Functional and structural brain changes in anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol 2013; 74 (02) 284-296.
• 12 Florance NR, Davis RL, Lam C. et al Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 2009; 66: 11-18.
• 13 Gabilondo I, Saiz A, Galan L. et al Analysis of relapses in anti-NMDAR encephalitis. Neurology 2011; 77: 996-999.
• 14 Grau-Rivera O, Sanchez-Valle R, Saiz A. et al Determination of neuronal antibodies in suspected and definite creutzfeldt-jakob disease. JAMA Neurol 2014; 71: 74-78.
• 15 Graus F, Delattre JY, Antoine JC. et al Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 2004; 75: 1135-1140.
• 16 Graus F, Keime-Guibert F, Rene R. et al Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain 2001; 124: 1138-1148.
• 17 Gresa-Arribas N, Titulaer MJ, Torrents A. et al Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol 2014; 13: 167-177.
• 18 Hutchinson M, Waters P, McHugh J. et al Progressive encephalomyelitis, rigidity, and myoclonus: a novel glycine receptor antibody. Neurology 2008; 71: 1291-1292.
• 19 Irani SR, Alexander S, Waters P. et al Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan’s syndrome and acquired neuromyotonia. Brain 2010; 133: 2734-2748.
• 20 Irani SR, Michell AW, Lang B. et al Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 2011; 69: 892-900.
• 21 Irani SR, Pettingill P, Kleopa KA. et al Morvan syndrome: clinical and serological observations in 29 cases. Ann Neurol 2012; 72: 241-255.
• 22 Irani SR, Stagg CJ, Schott JM. et al Faciobrachial dystonic seizures: the influence of immunotherapy on seizure control and prevention of cognitive impairment in a broadening phenotype. Brain 2013; 136: 3151-3162.
• 23 Kruer MC, Hoeftberger R, Lim KY. et al Aggressive course in encephalitis with opsoclonus, ataxia, chorea, and seizures: the first pediatric case of gamma-aminobutyric acid type B receptor autoimmunity. JAMA Neurol 2014; 71: 620-623.
• 24 Lai M, Huijbers MG, Lancaster E. et al Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol 2010; 9: 776-785.
• 25 Lancaster E, Lai M, Peng X. et al Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen. Lancet Neurology 2010; 9: 67-76.
• 26 Lancaster E, Martinez-Hernandez E, Titulaer MJ. Antibodies to metabotropic glutamate receptor 5 in the Ophelia syndrome. Neurology 2011; 77: 1698-1701.
• 27 Leypoldt F, Buchert R, Kleiter I. et al Fluorodeoxyglucose positron emission tomography in anti-N-methyl-D-aspartate receptor encephalitis: distinct pattern of disease. J Neurol Neurosurg Psychiatry 2012; 83: 681-686.
• 28 McKeon A, Martinez-Hernandez E, Lancaster E. et al Glycine Receptor Autoimmune Spectrum With Stiff-Man Syndrome Phenotype. Arch Neurol 2012; 1-9.
• 29 Moscato EH, Peng X, Jain A. et al Acute mechanisms underlying antibody effects in anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol 2014; 76: 108-119.
• 30 Petit-Pedrol M, Armangue T, Peng X. et al Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodies. Lancet Neurol 2014; 13: 276-286.
• 31 Prüss H, Dalmau J, Arolt V, Wandinger KP. [Anti-NMDA-receptor encephalitis. An interdisciplinary clinical picture]. Nervenarzt 2010; 81: 396-406.
• 32 Prüss H, Dalmau J, Harms L. et al Retrospective analysis of NMDA receptor antibodies in encephalitis of unknown origin. Neurology 2010; 75: 1735-1739.
• 33 Prüss H, Finke C, Höltje M. et al N-methyl-D-aspartate receptor antibodies in herpes simplex encephalitis. Annals of Neurology 2012; 72: 902-911.
• 34 Prüss H, Hoffmann C, Stenzel W. et al A case of inflammatory peripheral nerve destruction antedating anti-NMDA receptor encephalitis. Neurol Neuroimmunol Neuroinflamm 2014; 1: e14.
• 35 Prüss H, Rothkirch M, Kopp U. et al Limbic encephalitis with mGluR5 antibodies and immunotherapy-responsive prosopagnosia. Neurology 2014; 83: 1384-1386.
• 36 Sabater L, Gaig C, Gelpi E. et al A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON 5: a case series, characterisation of the antigen, and post-mortem study. The Lancet Neurology 2014; 13: 575-586.
• 37 Schäbitz WR, Rogalewski A, Hagemeister C, Bien CG. VZV brainstem encephalitis triggers NMDA receptor immunoreaction. Neurology 2014; 83: 2309-2311.
• 38 Schmitt SE, Pargeon K, Frechette ES. et al Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology 2012; 79: 1094-1100.
• 39 Stöcker W, Saschenbrecker S, Rentzsch K. et al [Autoantibody diagnostics in neurology using native and recombinant antigenic substrates]. Nervenarzt 2013; 84: 471-476.
• 40 Titulaer MJ, McCracken L, Gabilondo I. et al Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 2013; 12: 157-165.
• 41 Titulaer MJ, Soffietti R, Dalmau J. et al Screening for tumours in paraneoplastic syndromes: report of an EFNS task force. Eur J Neurol 2011; 18: e19-e13.
• 42 Vincent A, Buckley C, Schott JM. et al Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain 2004; 127: 701-712.