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Semin Neurol 2018; 38(03): 392-402
DOI: 10.1055/s-0038-1660819
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Diagnostic and Therapeutic Approach to Autoimmune Neurologic Disorders

A. Sebastian López-Chiriboga
1   Department of Neurology, Mayo Clinic, Rochester, Minnesota
,
Eoin P. Flanagan
1   Department of Neurology, Mayo Clinic, Rochester, Minnesota
› Author Affiliations
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Publication History

Publication Date:
16 July 2018 (online)

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Abstract

The field of autoimmune neurology is evolving rapidly. The discovery of autoantibodies that target neural antigens has expanded swiftly in the last decade. Recognition of the clinical syndromes associated with autoimmune neurologic disorders, and our understanding of the pathophysiology, has progressed significantly. Radiographic, electrophysiological, and laboratory testing (particularly neural autoantibody testing) are fundamental in the diagnosis of autoimmune neurological disorders and in the exclusion of mimics. Furthermore, investigations may serve as a baseline from which objective assessment of improvement or detection of relapse can be made. These disorders can be associated with underlying neoplasms, and screening for malignancy is an essential component of the investigations. Early diagnosis and prompt initiation of immunotherapy can improve neurologic function. The use of immunotherapy, however, can be associated with diverse side effects, and careful monitoring is crucial to prevent complications. Herein the authors address the diagnostic and treatment approach of autoimmune neurologic disorders, with particular focus on antibody-mediated neurologic autoimmunity.

Keywords

autoimmune encephalitis - immunotherapy - immunosuppressive medications - autoimmune neurology
 

  • References

  • 1 Pittock SJ, Palace J. Paraneoplastic and idiopathic autoimmune neurologic disorders: approach to diagnosis and treatment. Handb Clin Neurol 2016; 133: 165-183
    PubMedGoogle Scholar
  • 2 Dubey D, Pittock SJ, Kelly CR. , et al. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol 2018; 83 (01) 166-177
    CrossrefPubMedGoogle Scholar
  • 3 Yshii LM, Hohlfeld R, Liblau RS. Inflammatory CNS disease caused by immune checkpoint inhibitors: status and perspectives. Nat Rev Neurol 2017; 13 (12) 755-763
    CrossrefPubMedGoogle Scholar
  • 4 McKeon A. Autoimmune encephalopathies and dementias. Continuum (Minneap Minn) 2016; 22 (2 Dementia): 538-558
    PubMedGoogle Scholar
  • 5 Armangue T, Leypoldt F, Dalmau J. Autoimmune encephalitis as differential diagnosis of infectious encephalitis. Curr Opin Neurol 2014; 27 (03) 361-368
    CrossrefPubMedGoogle Scholar
  • 6 Dalmau J, Vincent A. Do we need to measure specific antibodies in patients with limbic encephalitis?. Neurology 2017; 88 (06) 508-509
    CrossrefPubMedGoogle Scholar
  • 7 Lancaster E. The diagnosis and treatment of autoimmune encephalitis. J Clin Neurol 2016; 12 (01) 1-13
    CrossrefPubMedGoogle Scholar
  • 8 Graus F, Delattre JY, Antoine JC. , et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 2004; 75 (08) 1135-1140
    CrossrefPubMedGoogle Scholar
  • 9 Feldt-Rasmussen U. Analytical and clinical performance goals for testing autoantibodies to thyroperoxidase, thyroglobulin, and thyrotropin receptor. Clin Chem 1996; 42 (01) 160-163
    PubMedGoogle Scholar
  • 10 Waters P, Pettingill P, Lang B. Detection methods for neural autoantibodies. Handb Clin Neurol 2016; 133: 147-163
    PubMedGoogle Scholar
  • 11 McKeon A, Pittock SJ, Lennon VA. CSF complements serum for evaluating paraneoplastic antibodies and NMO-IgG. Neurology 2011; 76 (12) 1108-1110
    CrossrefPubMedGoogle Scholar
  • 12 Majed M, Fryer JP, McKeon A, Lennon VA, Pittock SJ. Clinical utility of testing AQP4-IgG in CSF: guidance for physicians. Neurol Neuroimmunol Neuroinflamm 2016; 3 (03) e231
    CrossrefPubMedGoogle Scholar
  • 13 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 (02) 157-165
    CrossrefPubMedGoogle Scholar
  • 14 McKeon A. Immunotherapeutics for autoimmune encephalopathies and dementias. Curr Treat Options Neurol 2013; 15 (06) 723-737
    CrossrefPubMedGoogle Scholar
  • 15 Dubey D, Singh J, Britton JW. , et al. Predictive models in the diagnosis and treatment of autoimmune epilepsy. Epilepsia 2017; 58 (07) 1181-1189
    CrossrefPubMedGoogle Scholar
  • 16 Escudero D, Guasp M, Ariño H. , et al. Antibody-associated CNS syndromes without signs of inflammation in the elderly. Neurology 2017; 89 (14) 1471-1475
    CrossrefPubMedGoogle Scholar
  • 17 Heine J, Prüss H, Bartsch T, Ploner CJ, Paul F, Finke C. Imaging of autoimmune encephalitis--relevance for clinical practice and hippocampal function. Neuroscience 2015; 309: 68-83
    CrossrefPubMedGoogle Scholar
  • 18 Peer M, Prüss H, Ben-Dayan I, Paul F, Arzy S, Finke C. Functional connectivity of large-scale brain networks in patients with anti-NMDA receptor encephalitis: an observational study. Lancet Psychiatry 2017; 4 (10) 768-774
    PubMedGoogle Scholar
  • 19 Probasco JC, Solnes L, Nalluri A. , et al. Decreased occipital lobe metabolism by FDG-PET/CT: an anti-NMDA receptor encephalitis biomarker. Neurol Neuroimmunol Neuroinflamm 2017; 5 (01) e413
    PubMedGoogle Scholar
  • 20 Flanagan EP, Kotsenas AL, Britton JW. , et al. Basal ganglia T1 hyperintensity in LGI1-autoantibody faciobrachial dystonic seizures. Neurol Neuroimmunol Neuroinflamm 2015; 2 (06) e161
    CrossrefPubMedGoogle Scholar
  • 21 Finke C, Prüss H, Heine J. , et al. Evaluation of cognitive deficits and structural hippocampal damage in encephalitis with leucine-rich, glioma-inactivated 1 antibodies. JAMA Neurol 2017; 74 (01) 50-59
    CrossrefPubMedGoogle Scholar
  • 22 López Chiriboga AS, Siegel JL, Tatum WO, Shih JJ, Flanagan EP. Striking basal ganglia imaging abnormalities in LGI1 ab faciobrachial dystonic seizures. Neurol Neuroimmunol Neuroinflamm 2017; 4 (03) e336
    CrossrefPubMedGoogle Scholar
  • 23 Höftberger 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 (17) 1500-1506
    CrossrefPubMedGoogle Scholar
  • 24 Höftberger R, van Sonderen A, Leypoldt F. , et al. Encephalitis and AMPA receptor antibodies: novel findings in a case series of 22 patients. Neurology 2015; 84 (24) 2403-2412
    CrossrefPubMedGoogle Scholar
  • 25 Spatola M, Petit-Pedrol M, Simabukuro MM. , et al. Investigations in GABAA receptor antibody-associated encephalitis. Neurology 2017; 88 (11) 1012-1020
    CrossrefPubMedGoogle Scholar
  • 26 Flanagan EP, Hinson SR, Lennon VA. , et al. Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: analysis of 102 patients. Ann Neurol 2017; 81 (02) 298-309
    CrossrefPubMedGoogle Scholar
  • 27 Honorat JA, McKeon A. Autoimmune movement disorders: a clinical and laboratory approach. Curr Neurol Neurosci Rep 2017; 17 (01) 4
    CrossrefPubMedGoogle Scholar
  • 28 Dalmau J, Graus F, Villarejo A. , et al. Clinical analysis of anti-Ma2-associated encephalitis. Brain 2004; 127 (Pt 8): 1831-1844
    CrossrefPubMedGoogle Scholar
  • 29 Pittock SJ, Weinshenker BG, Lucchinetti CF, Wingerchuk DM, Corboy JR, Lennon VA. Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression. Arch Neurol 2006; 63 (07) 964-968
    CrossrefPubMedGoogle Scholar
  • 30 Lopez-Chiriboga AS, Komorowski L, Kümpfel T. , et al. Metabotropic glutamate receptor type 1 autoimmunity: clinical features and treatment outcomes. Neurology 2016; 86 (11) 1009-1013
    CrossrefPubMedGoogle Scholar
  • 31 Tobin WO, Lennon VA, Komorowski L. , et al. DPPX potassium channel antibody: frequency, clinical accompaniments, and outcomes in 20 patients. Neurology 2014; 83 (20) 1797-1803
    CrossrefPubMedGoogle Scholar
  • 32 Carvajal-González A, Leite MI, Waters P. , et al. Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes. Brain 2014; 137 (Pt 8): 2178-2192
    CrossrefPubMedGoogle Scholar
  • 33 Juryńczyk M, Tackley G, Kong Y. , et al. Brain lesion distribution criteria distinguish MS from AQP4-antibody NMOSD and MOG-antibody disease. J Neurol Neurosurg Psychiatry 2017; 88 (02) 132-136
    CrossrefPubMedGoogle Scholar
  • 34 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
    PubMedGoogle Scholar
  • 35 Baumgartner A, Rauer S, Mader I, Meyer PT. Cerebral FDG-PET and MRI findings in autoimmune limbic encephalitis: correlation with autoantibody types. J Neurol 2013; 260 (11) 2744-2753
    CrossrefPubMedGoogle Scholar
  • 36 Probasco JC, Solnes L, Nalluri A. , et al. Abnormal brain metabolism on FDG-PET/CT is a common early finding in autoimmune encephalitis. Neurol Neuroimmunol Neuroinflamm 2017; 4 (04) e352
    CrossrefPubMedGoogle Scholar
  • 37 Ariño H, Armangué T, Petit-Pedrol M. , et al. Anti-LGI1-associated cognitive impairment: Presentation and long-term outcome. Neurology 2016; 87 (08) 759-765
    CrossrefPubMedGoogle Scholar
  • 38 Toledano M, Pittock SJ. Autoimmune epilepsy. Semin Neurol 2015; 35 (03) 245-258
    Article in Thieme ConnectPubMedGoogle Scholar
  • 39 Schmitt SE, Pargeon K, Frechette ES, Hirsch LJ, Dalmau J, Friedman D. Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology 2012; 79 (11) 1094-1100
    CrossrefPubMedGoogle Scholar
  • 40 Gadoth A, Pittock SJ, Dubey D. , et al. Expanded phenotypes and outcomes among 256 LGI1/CASPR2-IgG-positive patients. Ann Neurol 2017; 82 (01) 79-92
    CrossrefPubMedGoogle Scholar
  • 41 Mckeon A, Benarroch EE. Autoimmune autonomic disorders. Handb Clin Neurol 2016; 133: 405-416
    CrossrefPubMedGoogle Scholar
  • 42 Flanagan EP, Saito YA, Lennon VA. , et al. Immunotherapy trial as diagnostic test in evaluating patients with presumed autoimmune gastrointestinal dysmotility. Neurogastroenterol Motil 2014; 26 (09) 1285-1297
    CrossrefPubMedGoogle Scholar
  • 43 Manogaran P, Hanson JV, Olbert ED. , et al. Optical coherence tomography and magnetic resonance imaging in multiple sclerosis and neuromyelitis optica spectrum disorder. Int J Mol Sci 2016; 17 (11) 17
    CrossrefPubMedGoogle Scholar
  • 44 Adamus G. Autoantibody targets and their cancer relationship in the pathogenicity of paraneoplastic retinopathy. Autoimmun Rev 2009; 8 (05) 410-414
    CrossrefPubMedGoogle Scholar
  • 45 Matsumoto JY, Caviness JN, McEvoy KM. The acoustic startle reflex in stiff-man syndrome. Neurology 1994; 44 (10) 1952-1955
    CrossrefPubMedGoogle Scholar
  • 46 Flanagan EP, McKeon A, Lennon VA. , et al. Autoimmune dementia: clinical course and predictors of immunotherapy response. Mayo Clin Proc 2010; 85 (10) 881-897
    CrossrefPubMedGoogle Scholar
  • 47 Högl B, Heidbreder A, Santamaria J, Graus F, Poewe W. IgLON5 autoimmunity and abnormal behaviours during sleep. Lancet 2015; 385 (9977): 1590
    CrossrefPubMedGoogle Scholar
  • 48 Pittock SJ, Parisi JE, McKeon A. , et al. Paraneoplastic jaw dystonia and laryngospasm with antineuronal nuclear autoantibody type 2 (anti-Ri). Arch Neurol 2010; 67 (09) 1109-1115
    PubMedGoogle Scholar
  • 49 Zekeridou A, Lennon VA. Aquaporin-4 autoimmunity. Neurol Neuroimmunol Neuroinflamm 2015; 2 (04) e110
    CrossrefPubMedGoogle Scholar
  • 50 Honorat JA, Komorowski L, Josephs KA. , et al. IgLON5 antibody: neurological accompaniments and outcomes in 20 patients. Neurol Neuroimmunol Neuroinflamm 2017; 4 (05) e385
    CrossrefPubMedGoogle Scholar
  • 51 Schubert RD, Wilson MR. A tale of two approaches: how metagenomics and proteomics are shaping the future of encephalitis diagnostics. Curr Opin Neurol 2015; 28 (03) 283-287
    CrossrefPubMedGoogle Scholar
  • 52 McKeon A, Apiwattanakul M, Lachance DH. , et al. Positron emission tomography-computed tomography in paraneoplastic neurologic disorders: systematic analysis and review. Arch Neurol 2010; 67 (03) 322-329
    CrossrefPubMedGoogle Scholar
  • 53 Titulaer MJ, Soffietti R, Dalmau J. , et al; European Federation of Neurological Societies. Screening for tumours in paraneoplastic syndromes: report of an EFNS task force. Eur J Neurol 2011; 18 (01) 19-e3
    CrossrefPubMedGoogle Scholar
  • 54 van Sonderen A, Roelen DL, Stoop JA. , et al. Anti-LGI1 encephalitis is strongly associated with HLA-DR7 and HLA-DRB4. Ann Neurol 2017; 81 (02) 193-198
    CrossrefPubMedGoogle Scholar
  • 55 Tobin WO, Pittock SJ. Autoimmune neurology of the central nervous system. Continuum (Minneap Minn) 2017; 23 (3, Neurology of Systemic Disease): 627-653
    PubMedGoogle Scholar
  • 56 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 (02) 167-177
    CrossrefPubMedGoogle Scholar
  • 57 Feyissa AM, López Chiriboga AS, Britton JW. Antiepileptic drug therapy in patients with autoimmune epilepsy. Neurol Neuroimmunol Neuroinflamm 2017; 4 (04) e353
    CrossrefPubMedGoogle Scholar
  • 58 Dubey D, Blackburn K, Greenberg B, Stuve O, Vernino S. Diagnostic and therapeutic strategies for management of autoimmune encephalopathies. Expert Rev Neurother 2016; 16 (08) 937-949
    CrossrefPubMedGoogle Scholar
  • 59 McKeon A, Pittock SJ. Paraneoplastic encephalomyelopathies: pathology and mechanisms. Acta Neuropathol 2011; 122 (04) 381-400
    CrossrefPubMedGoogle Scholar
  • 60 Kleiter I, Gahlen A, Borisow N. , et al; Neuromyelitis Optica Study Group. Neuromyelitis optica: Evaluation of 871 attacks and 1,153 treatment courses. Ann Neurol 2016; 79 (02) 206-216
    CrossrefPubMedGoogle Scholar
  • 61 Vodopivec I, Miloslavsky EM, Kotton CN, Cho TA. A neurologist's guide to safe use of immunomodulatory therapies. Semin Neurol 2014; 34 (04) 467-478
    Article in Thieme ConnectPubMedGoogle Scholar
  • 62 Mitchell K, Kaul M, Clowse ME. The management of rheumatic diseases in pregnancy. Scand J Rheumatol 2010; 39 (02) 99-108
    CrossrefPubMedGoogle Scholar
  • 63 Pittock SJ, Lennon VA, McKeon A. , et al. Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study. Lancet Neurol 2013; 12 (06) 554-562
    CrossrefPubMedGoogle Scholar
  • 64 Lee WJ, Lee ST, Moon J. , et al. Tocilizumab in autoimmune encephalitis refractory to rituximab: an institutional cohort study. Neurotherapeutics 2016; 13 (04) 824-832
    CrossrefPubMedGoogle Scholar
  • 65 Zhang C, Tian DC, Yang CS. , et al. Safety and efficacy of bortezomib in patients with highly relapsing neuromyelitis optica spectrum disorder. JAMA Neurol 2017; 74 (08) 1010-1012
    CrossrefPubMedGoogle Scholar
  • 66 Scheibe F, Prüss H, Mengel AM. , et al. Bortezomib for treatment of therapy-refractory anti-NMDA receptor encephalitis. Neurology 2017; 88 (04) 366-370
    CrossrefPubMedGoogle Scholar
  • 67 Dogan Onugoren M, Golombeck KS, Bien C. , et al. Immunoadsorption therapy in autoimmune encephalitides. Neurol Neuroimmunol Neuroinflamm 2016; 3 (02) e207
    CrossrefPubMedGoogle Scholar