Updates in the Diagnosis and Treatment of Paraneoplastic Neurologic Syndromes
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The disorders of the central nervous system associated with cancer by remote immune-mediated mechanisms are a heterogeneous group. These disorders encompass the classic paraneoplastic disorders and the recently recognized autoimmune encephalitis associated with antibodies against neuronal cell surface or synaptic proteins that occur with or without cancer association. In the last decade, the new surge of interest in neuronal diseases associated with anti-neuronal antibodies led to the rapid discovery of new forms of disease that have different manifestations and were not previously suspected to be immune mediated. The recognition of these syndromes is important because it may lead to early detection of an underlying malignancy and prompt initiation of treatment, improving chances for a better outcome.
KeywordsLimbic encephalitis Onconeuronal antibodies Paraneoplastic neurological syndromes Paraneoplastic encephalomyelitis Paraneoplastic cerebellar degeneration Autoimmune encephalitis Stiff person syndrome Progressive encephalomyelitis with rigidity and myoclonus Opsoclonus-myoclonus syndrome Morvan syndrome Ophelia syndrome N-methyl-d-aspartate receptor (NMDAR) encephalitis Anti-AMPA receptor (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) encephalitis Anti-GABAbR (γ-aminobutyric acid receptor-B) encephalitis Anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis Anti-Caspr2 encephalitis (contactin-associated protein-like 2) Anti-glycine receptor (GlyR) antibodies Anti-mGluR5 (metabotropic glutamate receptor 5) Anti-mGLUR1 (metabotropic glutamate receptor 1) Anti-Hu antibodies Anti-Ma2 antibodies Anti-DNER (Delta/Notch-like epidermal growth factor-related receptor) antibodies Anti-CV2/CRMP5 antibodies
Compliance with Ethical Standards
Conflict of Interest
Ronnyson Susano Grativvol declares that he has no conflict of interest.
Wagner Cid Palmeira Cavalcante declares that he has no conflict of interest.
Luiz Henrique Martins Castro declares that he has no conflict of interest.
Ricardo Nitrini has received research funding from FAPESP, has served on advisory boards for Janssen-Cilag and Brazilian Nutricia, has received travel funding and reimbursement from Novartis, serves as an editor for Dementia & Neuropsychologia, serves on the editorial board for Alzheimer’s Disease & Associated Disorders and International Journal of Alzheimer’s Disease, and has served as a guest speaker for Novartis and Danone (Nutricia).
Mateus Mistieri Simabukuro declares that he has no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.Lancaster E. Paraneoplastic disorders. Contin Minneap Minn. 2015;21(2 Neuro-oncology):452–75.Google Scholar
- 5.Brain WR, Norris FH. The remote effects of cancer on the nervous system. New York: Grune and Stratton; 1965.Google Scholar
- 18.Irani SR, Alexander S, Waters P, Kleopa KA, Pettingill P, Zuliani L, 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(9):2734–48.CrossRefGoogle Scholar
- 22.Sabater L, Gaig C, Gelpi E, Bataller L, Lewerenz J, Torres-Vega E, et al. A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study. Lancet Neurol. 2014;13(6):575–86.CrossRefGoogle Scholar
- 37.•• Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391–404. A position letter based on literature review and gathered the experience of a team of experts with the aims of developing a practical, syndrome-based diagnostic approach to autoimmune encephalitis and providing guidelines to navigate through the differential diagnosis CrossRefGoogle Scholar
- 43.Honnorat J, Cartalat-Carel S, Ricard D, Camdessanche JP, Carpentier AF, Rogemond V, et al. Onco-neural antibodies and tumour type determine survival and neurological symptoms in paraneoplastic neurological syndromes with Hu or CV2/CRMP5 antibodies. J Neurol Neurosurg Psychiatry. 2009 Apr;80(4):412–416.CrossRefGoogle Scholar
- 47.Sabater L, Höftberger R, Boronat A, Saiz A, Dalmau J, Graus F. Antibody Repertoire in Paraneoplastic Cerebellar Degeneration and Small Cell Lung Cancer. PLOS ONE. 2013 Mar 25;8(3):e60438.Google Scholar
- 50.Marignier R, Chenevier F, Rogemond V, et al. Metabotropic glutamate receptor type 1 autoantibody–associated cerebellitis: A primary autoimmune disease? Arch Neurol. 2010 May 1;67(5):627–630.Google Scholar
- 52.• Lopez-Chiriboga AS, Komorowski L, Kümpfel T, Probst C, Hinson SR, Pittock SJ, et al. Metabotropic glutamate receptor type 1 autoimmunity Clinical features and treatment outcomes. Neurology. 2016 Mar 15;86(11):1009–1013. It retrospectively describes the clinical associations of immunoglobulin G (IgG) targeting metabotropic glutamate receptor 1 (mGluR1-IgG). The largest series of patients with mGLUr1 ataxia.CrossRefGoogle Scholar
- 54.• van Sonderen A, Thijs RD, Coenders EC, Jiskoot LC, Sanchez E, de Bruijn MAAM, et al. Anti-LGI1 encephalitis: Clinical syndrome and long-term follow-up. Neurology. 2016 Oct 4;87(14):1449–1456. A nationwide study; a detailed description of the clinical features and long-term outcome of a LGI1 encephalitis. Google Scholar
- 55.• Ariño H, Armangué T, Petit-Pedrol M, Sabater L, Martinez-Hernandez E, Hara M, et al. Anti-LGI1–associated cognitive impairment Presentation and long-term outcome. Neurology. 2016 Aug 23;87(8):759–765. This paper determines the clinical presentation, long-term outcome, and LGI1 encephalitis evolution. CrossRefGoogle Scholar
- 56.van Sonderen A, Ariño H, Petit-Pedrol M, Leypoldt F, Körtvélyessy P, Wandinger K-P, et al. The clinical spectrum of Caspr2 antibody-associated disease. Neurology. 2016 Aug 2;87(5):521–528.Google Scholar
- 63.• Armangué T, Sabater L, Torres-Vega E, Martínez-Hernández E, Ariño H, Petit-Pedrol M, et al. Clinical and Immunological Features of Opsoclonus-Myoclonus Syndrome in the Era of Neuronal Cell Surface Antibodies. JAMA Neurol. 2016 Apr;73(4):417–424. Report of the clinical and immunological features of idiopathic OMS (I-OMS) andparaneoplastic OMS (P-OMS), the occurrence of antibodies to cell surface antigens, and the discovery of a novel cell surface epitope.CrossRefGoogle Scholar
- 64.Bataller L, Graus F, Saiz A, Vilchez JJ, Spanish Opsoclonus-Myoclonus Study Group. Clinical outcome in adult onset idiopathic or paraneoplastic opsoclonus-myoclonus. Brain J Neurol. 2001 Feb;124(Pt 2):437–443.Google Scholar
- 69.Carvajal-González A, Leite MI, Waters P, Woodhall M, Coutinho E, Balint B, et al. Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes. Brain. 2014 Aug Google Scholar
- 72.Petit-Pedrol M, Armangue T, Peng X, Bataller L, Cellucci T, Davis R, 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(3):276–86.CrossRefGoogle Scholar
- 73.• Titulaer MJ, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort . Lancet Neurol. 2013;12(2):157–65. The largest cohort of patients. It assesses the presentation of the disease, the spectrum of symptoms, immunotherapies used, timing of improvement, and long-term outcome.Google Scholar
- 76.•• Dalmau J, Graus F. Antibody-Mediated Encephalitis. Ropper AH, editor. N Engl J Med. 2018 Mar;378(9):840–851. Outstanding review of the autoimmune encephalitis syndromes Google Scholar