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Semin Neurol 2016; 36(04): 382-396
DOI: 10.1055/s-0036-1585453
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Autoantibody-Associated Central Nervous System Neurologic Disorders

Jenny Linnoila
1   Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts
,
Sean J. Pittock
2   Department of Laboratory Medicine/Pathology, Mayo Clinic, College of Medicine, Rochester, Minnesota
3   Department of Neurology, Mayo Clinic, College of Medicine, Rochester, Minnesota
› Author Affiliations
Further Information

Publication History

Publication Date:
19 September 2016 (online)

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Abstract

Autoimmune neurology is a rapidly evolving new subspecialty driven by the discovery of novel neural- (neuronal- or glial-) specific autoantibodies and their target antigens. The neurologic manifestations affecting the central nervous system include encephalitis, dementia, epilepsy, and movement and sleep disorders. Laboratory testing is now available for most of these neural-specific autoantibodies, which serve as diagnostic markers, in some instances directing the physician toward specific cancer types (e.g., N-methyl-D-aspartic acid receptor antibodies for teratoma, collapsin response mediator protein 5 for small-cell lung cancer) and assisting in therapeutic decision making. Antibodies targeting intracellular proteins serve as markers of cytotoxic effector T-cell-mediated injury, which is generally poorly responsive to immunotherapy. By contrast, antibodies targeting extracellular plasma membrane proteins may act as pathogenic effectors and often infer good responses to immunotherapy. Diagnosing these conditions and implementing treatment as early into the clinical course as possible ensures the best possible clinical outcomes. An adequate immunotherapy trial to assess maximum reversibility of symptoms, as assessed through objective functional measures, is crucial and can help to determine whether maintenance therapy is needed.

Keywords

paraneoplastic - autoimmune - encephalitis - antibodies - immunotherapy
 

  • References

  • 1 Titulaer MJ, Höftberger R, Iizuka T , et al. Overlapping demyelinating syndromes and anti–N-methyl-D-aspartate receptor encephalitis. Ann Neurol 2014; 75 (3) 411-428
    CrossrefPubMedGoogle Scholar
  • 2 Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med 2003; 349 (16) 1543-1554
    CrossrefPubMedGoogle Scholar
  • 3 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
  • 4 Vora NM, Holman RC, Mehal JM, Steiner CA, Blanton J, Sejvar J. Burden of encephalitis-associated hospitalizations in the United States, 1998-2010. Neurology 2014; 82 (5) 443-451
    CrossrefPubMedGoogle Scholar
  • 5 Kramer AH. Viral encephalitis in the ICU. Crit Care Clin 2013; 29 (3) 621-649
    CrossrefPubMedGoogle Scholar
  • 6 Prüss H, Dalmau J, Harms L , et al. Retrospective analysis of NMDA receptor antibodies in encephalitis of unknown origin. Neurology 2010; 75 (19) 1735-1739
    CrossrefPubMedGoogle Scholar
  • 7 Prüss H, Finke C, Höltje M , et al. N-methyl-D-aspartate receptor antibodies in herpes simplex encephalitis. Ann Neurol 2012; 72 (6) 902-911
    CrossrefPubMedGoogle Scholar
  • 8 Höftberger R, Armangue T, Leypoldt F, Graus F, Dalmau J. Clinical Neuropathology practice guide 4-2013: post-herpes simplex encephalitis: N-methyl-D-aspartate receptor antibodies are part of the problem. Clin Neuropathol 2013; 32 (4) 251-254
    CrossrefPubMedGoogle Scholar
  • 9 Leypoldt F, Titulaer MJ, Aguilar E , et al. Herpes simplex virus-1 encephalitis can trigger anti-NMDA receptor encephalitis: case report. Neurology 2013; 81 (18) 1637-1639
    CrossrefPubMedGoogle Scholar
  • 10 Armangue T, Leypoldt F, Málaga I , et al. Herpes simplex virus encephalitis is a trigger of brain autoimmunity. Ann Neurol 2014; 75 (2) 317-323
    CrossrefPubMedGoogle Scholar
  • 11 Hacohen Y, Deiva K, Pettingill P , et al. N-methyl-D-aspartate receptor antibodies in post-herpes simplex virus encephalitis neurological relapse. Mov Disord 2014; 29 (1) 90-96
    CrossrefPubMedGoogle Scholar
  • 12 Mohammad SS, Sinclair K, Pillai S , et al. Herpes simplex encephalitis relapse with chorea is associated with autoantibodies to N-Methyl-D-aspartate receptor or dopamine-2 receptor. Mov Disord 2014; 29 (1) 117-122
    CrossrefPubMedGoogle Scholar
  • 13 Titulaer MJ, Leypoldt F, Dalmau J. Antibodies to N-methyl-D-aspartate and other synaptic receptors in choreoathetosis and relapsing symptoms post-herpes virus encephalitis. Mov Disord 2014; 29 (1) 3-6
    CrossrefPubMedGoogle Scholar
  • 14 Schäbitz WR, Rogalewski A, Hagemeister C, Bien CG. VZV brainstem encephalitis triggers NMDA receptor immunoreaction. Neurology 2014; 83 (24) 2309-2311
    CrossrefPubMedGoogle Scholar
  • 15 Armangue T, Moris G, Cantarin-Extremera V , et al. Autoimmune post-herpes simplex encephalitis of adults and teenagers. Neurology 2015; 85 (20) 1736-1743
    CrossrefPubMedGoogle Scholar
  • 16 Morris NA, Kaplan TB, Linnoila J , et al. HSV encephalitis-induced anti-NMDAR encephalitis in a 67-year-old woman: report of a case and review of the literature. J Neurovirol 2016; 22 (1) 33-37
    CrossrefPubMedGoogle Scholar
  • 17 Linnoila JJ, Binnicker MJ, Majed M , et al. CSF herpes virus and autoantibody profiles in the evaluation of encephalitis. Neurol Neuroimmunol Neuroinflamm 2016; 3 (4) e245
    PubMedGoogle Scholar
  • 18 Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Dalmau J. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain 2000; 123 (Pt 7): 1481-1494
    CrossrefPubMedGoogle Scholar
  • 19 Pittock SJ, Lucchinetti CF, Parisi JE , et al. Amphiphysin autoimmunity: paraneoplastic accompaniments. Ann Neurol 2005; 58 (1) 96-107
    CrossrefPubMedGoogle Scholar
  • 20 Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 2005; 202 (4) 473-477
    CrossrefPubMedGoogle Scholar
  • 21 Dalmau J, Tüzün E, Wu HY , et al. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007; 61 (1) 25-36
    Google Scholar
  • 22 Hutchinson M, Waters P, McHugh J , et al. Progressive encephalomyelitis, rigidity, and myoclonus: a novel glycine receptor antibody. Neurology 2008; 71 (16) 1291-1292
    CrossrefPubMedGoogle Scholar
  • 23 Lai M, Hughes EG, Peng X , et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol 2009; 65 (4) 424-434
    CrossrefPubMedGoogle Scholar
  • 24 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 Neurol 2010; 9 (1) 67-76
    CrossrefPubMedGoogle Scholar
  • 25 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 (9) 2734-2748
    CrossrefPubMedGoogle Scholar
  • 26 Lancaster E, Martinez-Hernandez E, Titulaer MJ , et al. Antibodies to metabotropic glutamate receptor 5 in the Ophelia syndrome. Neurology 2011; 77 (18) 1698-1701
    CrossrefPubMedGoogle Scholar
  • 27 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 (1) 120-128
    CrossrefPubMedGoogle Scholar
  • 28 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 (3) 276-286
    CrossrefPubMedGoogle Scholar
  • 29 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 IgLON5: a case series, characterisation of the antigen, and post-mortem study. Lancet Neurol 2014; 13 (6) 575-586
    CrossrefPubMedGoogle Scholar
  • 30 Hinson SR, Pittock SJ, Lucchinetti CF , et al. Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology 2007; 69 (24) 2221-2231
    CrossrefPubMedGoogle Scholar
  • 31 Hughes EG, Peng X, Gleichman AJ , et al. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci 2010; 30 (17) 5866-5875
    CrossrefPubMedGoogle Scholar
  • 32 Moscato EH, Peng X, Jain A, Parsons TD, Dalmau J, Balice-Gordon RJ. Acute mechanisms underlying antibody effects in anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol 2014; 76 (1) 108-119
    CrossrefPubMedGoogle Scholar
  • 33 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 (2) 157-165
    CrossrefPubMedGoogle Scholar
  • 34 McKeon A, Lennon VA, Pittock SJ. Immunotherapy-responsive dementias and encephalopathies. Continuum (Minneap Minn) 2010; 16 (2 Dementia): 80-101
    PubMedGoogle Scholar
  • 35 McKeon A, Marnane M, O'connell M, Stack JP, Kelly PJ, Lynch T. Potassium channel antibody associated encephalopathy presenting with a frontotemporal dementia like syndrome. Arch Neurol 2007; 64 (10) 1528-1530
    CrossrefPubMedGoogle Scholar
  • 36 Geschwind MD, Tan KM, Lennon VA , et al. Voltage-gated potassium channel autoimmunity mimicking creutzfeldt-jakob disease. Arch Neurol 2008; 65 (10) 1341-1346
    CrossrefPubMedGoogle Scholar
  • 37 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
  • 38 Quek AM, Britton JW, McKeon A , et al. Autoimmune epilepsy: clinical characteristics and response to immunotherapy. Arch Neurol 2012; 69 (5) 582-593
    CrossrefPubMedGoogle Scholar
  • 39 Toledano M, Britton JW, McKeon A , et al. Utility of an immunotherapy trial in evaluating patients with presumed autoimmune epilepsy. Neurology 2014; 82 (18) 1578-1586
    CrossrefPubMedGoogle Scholar
  • 40 Toledano M, Pittock SJ. Autoimmune Epilepsy. Semin Neurol 2015; 35 (3) 245-258
    Article in Thieme ConnectPubMedGoogle Scholar
  • 41 Russo C, Cohn SL, Petruzzi MJ, de Alarcon PA. Long-term neurologic outcome in children with opsoclonus-myoclonus associated with neuroblastoma: a report from the Pediatric Oncology Group. Med Pediatr Oncol 1997; 28 (4) 284-288
    CrossrefPubMedGoogle Scholar
  • 42 Klaas JP, Ahlskog JE, Pittock SJ , et al. Adult-onset opsoclonus-myoclonus syndrome. Arch Neurol 2012; 69 (12) 1598-1607
    CrossrefPubMedGoogle Scholar
  • 43 Bataller L, Graus F, Saiz A, Vilchez JJ ; Spanish Opsoclonus-Myoclonus Study Group. Clinical outcome in adult onset idiopathic or paraneoplastic opsoclonus-myoclonus. Brain 2001; 124 (Pt 2): 437-443
    CrossrefPubMedGoogle Scholar
  • 44 Bataller L, Dalmau J. Neuro-ophthalmology and paraneoplastic syndromes. Curr Opin Neurol 2004; 17 (1) 3-8
    CrossrefPubMedGoogle Scholar
  • 45 Cross SA, Salomao DR, Parisi JE , et al. Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG. Ann Neurol 2003; 54 (1) 38-50
    CrossrefPubMedGoogle Scholar
  • 46 Reindl M, Di Pauli F, Rostásy K, Berger T. The spectrum of MOG autoantibody-associated demyelinating diseases. Nat Rev Neurol 2013; 9 (8) 455-461
    CrossrefPubMedGoogle Scholar
  • 47 Heckenlively JR, Ferreyra HA. Autoimmune retinopathy: a review and summary. Semin Immunopathol 2008; 30 (2) 127-134
    CrossrefPubMedGoogle Scholar
  • 48 Bienia B, Balabanov R. Immunotherapy of neuromyelitis optica. Autoimmune Dis 2013; 2013: 741490
    PubMedGoogle Scholar
  • 49 Irani SR, Pettingill P, Kleopa KA , et al. Morvan syndrome: clinical and serological observations in 29 cases. Ann Neurol 2012; 72 (2) 241-255
    CrossrefPubMedGoogle Scholar
  • 50 Iranzo A, Graus F, Clover L , et al. Rapid eye movement sleep behavior disorder and potassium channel antibody-associated limbic encephalitis. Ann Neurol 2006; 59 (1) 178-181
    CrossrefPubMedGoogle Scholar
  • 51 Landolfi JC, Nadkarni M. Paraneoplastic limbic encephalitis and possible narcolepsy in a patient with testicular cancer: case study. Neuro-oncol 2003; 5 (3) 214-216
    PubMedGoogle Scholar
  • 52 Rojas-Marcos I, Graus F, Sanz G, Robledo A, Diaz-Espejo C. Hypersomnia as presenting symptom of anti-Ma2-associated encephalitis: case study. Neuro-oncol 2007; 9 (1) 75-77
    PubMedGoogle Scholar
  • 53 Adams C, McKeon A, Silber MH, Kumar R. Narcolepsy, REM sleep behavior disorder, and supranuclear gaze palsy associated with Ma1 and Ma2 antibodies and tonsillar carcinoma. Arch Neurol 2011; 68 (4) 521-524
    CrossrefPubMedGoogle Scholar
  • 54 Zekeridou A, Lennon VA. Aquaporin-4 autoimmunity. Neurol Neuroimmunol Neuroinflamm 2015; 2 (4) e110
    PubMedGoogle Scholar
  • 55 Vernino S, Tuite P, Adler CH , et al. Paraneoplastic chorea associated with CRMP-5 neuronal antibody and lung carcinoma. Ann Neurol 2002; 51 (5) 625-630
    CrossrefPubMedGoogle Scholar
  • 56 Panzer J, Dalmau J. Movement disorders in paraneoplastic and autoimmune disease. Curr Opin Neurol 2011; 24 (4) 346-353
    CrossrefPubMedGoogle Scholar
  • 57 Ben-Pazi H, Stoner JA, Cunningham MW. Dopamine receptor autoantibodies correlate with symptoms in Sydenham's chorea. PLoS ONE 2013; 8 (9) e73516
    CrossrefPubMedGoogle Scholar
  • 58 Lucchinetti CF, Kimmel DW, Lennon VA. Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies. Neurology 1998; 50 (3) 652-657
    CrossrefPubMedGoogle Scholar
  • 59 Jones AL, Flanagan EP, Pittock SJ , et al. Responses to and outcomes of treatment of autoimmune cerebellar ataxia in adults. JAMA Neurol 2015; 72 (11) 1304-1312
    CrossrefPubMedGoogle Scholar
  • 60 Shams'ili S, Grefkens J, de Leeuw B , et al. Paraneoplastic cerebellar degeneration associated with antineuronal antibodies: analysis of 50 patients. Brain 2003; 126 (Pt 6): 1409-1418
    CrossrefPubMedGoogle Scholar
  • 61 Peterson K, Rosenblum MK, Kotanides H, Posner JB. Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients. Neurology 1992; 42 (10) 1931-1937
    CrossrefPubMedGoogle Scholar
  • 62 Bernal F, Shams'ili S, Rojas I , et al. Anti-Tr antibodies as markers of paraneoplastic cerebellar degeneration and Hodgkin's disease. Neurology 2003; 60 (2) 230-234
    CrossrefPubMedGoogle Scholar
  • 63 Graus F, Lang B, Pozo-Rosich P, Saiz A, Casamitjana R, Vincent A. P/Q type calcium-channel antibodies in paraneoplastic cerebellar degeneration with lung cancer. Neurology 2002; 59 (5) 764-766
    CrossrefPubMedGoogle Scholar
  • 64 Sillevis Smitt P, Kinoshita A, De Leeuw B , et al. Paraneoplastic cerebellar ataxia due to autoantibodies against a glutamate receptor. N Engl J Med 2000; 342 (1) 21-27
    CrossrefPubMedGoogle Scholar
  • 65 Marignier R, Chenevier F, Rogemond V , et al. Metabotropic glutamate receptor type 1 autoantibody-associated cerebellitis: a primary autoimmune disease?. Arch Neurol 2010; 67 (5) 627-630
    PubMedGoogle Scholar
  • 66 Dalmau J, Graus F, Villarejo A , et al. Clinical analysis of anti-Ma2-associated encephalitis. Brain 2004; 127 (Pt 8) 1831-1844
    CrossrefPubMedGoogle Scholar
  • 67 McKeon A. Paraneoplastic and other autoimmune disorders of the central nervous system. Neurohospitalist 2013; 3 (2) 53-64
    PubMedGoogle Scholar
  • 68 Misu T, Fujihara K, Nakashima I, Sato S, Itoyama Y. Intractable hiccup and nausea with periaqueductal lesions in neuromyelitis optica. Neurology 2005; 65 (9) 1479-1482
    CrossrefPubMedGoogle Scholar
  • 69 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 (9) 1109-1115
    CrossrefPubMedGoogle Scholar
  • 70 Saiz A, Bruna J, Stourac P , et al. Anti-Hu-associated brainstem encephalitis. J Neurol Neurosurg Psychiatry 2009; 80 (4) 404-407
    CrossrefPubMedGoogle Scholar
  • 71 Lee KS, Higgins MJ, Patel BM, Larson JS, Rady MY. Paraneoplastic coma and acquired central alveolar hypoventilation as a manifestation of brainstem encephalitis in a patient with ANNA-1 antibody and small-cell lung cancer. Neurocrit Care 2006; 4 (2) 137-139
    CrossrefPubMedGoogle Scholar
  • 72 Yu Z, Kryzer TJ, Griesmann GE, Kim K, Benarroch EE, Lennon VA. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol 2001; 49 (2) 146-154
    CrossrefPubMedGoogle Scholar
  • 73 Dropcho EJ. Antiamphiphysin antibodies with small-cell lung carcinoma and paraneoplastic encephalomyelitis. Ann Neurol 1996; 39 (5) 659-667
    CrossrefPubMedGoogle Scholar
  • 74 Dalmau J, Gultekin SH, Voltz R , et al. Ma1, a novel neuron- and testis-specific protein, is recognized by the serum of patients with paraneoplastic neurological disorders. Brain 1999; 122 (Pt 1): 27-39
    CrossrefPubMedGoogle Scholar
  • 75 Flanagan EP, Weinshenker BG, Krecke KN , et al. Short myelitis lesions in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders. JAMA Neurol 2015; 72 (1) 81-87
    CrossrefPubMedGoogle Scholar
  • 76 Sato DK, Callegaro D, Lana-Peixoto MA , et al. Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology 2014; 82 (6) 474-481
    CrossrefPubMedGoogle Scholar
  • 77 Flanagan EP, McKeon A, Lennon VA , et al. Paraneoplastic isolated myelopathy: clinical course and neuroimaging clues. Neurology 2011; 76 (24) 2089-2095
    CrossrefPubMedGoogle Scholar
  • 78 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
  • 79 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 (Pt 10): 3151-3162
    CrossrefPubMedGoogle Scholar
  • 80 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 (2) 167-177
    CrossrefPubMedGoogle Scholar
  • 81 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 (3) 322-329
    CrossrefPubMedGoogle Scholar
  • 82 Pittock SJ, Kryzer TJ, Lennon VA. Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol 2004; 56 (5) 715-719
    CrossrefPubMedGoogle Scholar
  • 83 Hacohen Y, Wright S, Waters P , et al. Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens. J Neurol Neurosurg Psychiatry 2013; 84 (7) 748-755
    CrossrefPubMedGoogle Scholar
  • 84 Armangue T, Petit-Pedrol M, Dalmau J. Autoimmune encephalitis in children. J Child Neurol 2012; 27 (11) 1460-1469
    CrossrefPubMedGoogle Scholar
  • 85 Lindstrom JM, Seybold ME, Lennon VA, Whittingham S, Duane DD. Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value. Neurology 1976; 26 (11) 1054-1059
    CrossrefPubMedGoogle Scholar
  • 86 Kimbrough DJ, Fujihara K, Jacob A , et al; GJCF-CC&BR. Treatment of neuromyelitis optica: review and recommendations. Mult Scler Relat Disord 2012; 1 (4) 180-187
    CrossrefPubMedGoogle Scholar
  • 87 Vincent A, Buckley C, Schott JM , et al. Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain 2004; 127 (Pt 3): 701-712
    CrossrefPubMedGoogle Scholar
  • 88 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 (12) 1161-1166
    CrossrefPubMedGoogle Scholar
  • 89 Paterson RW, Zandi MS, Armstrong R, Vincent A, Schott JM. Clinical relevance of positive voltage-gated potassium channel (VGKC)-complex antibodies: experience from a tertiary referral centre. J Neurol Neurosurg Psychiatry 2014; 85 (6) 625-630
    CrossrefPubMedGoogle Scholar
  • 90 Klein CJ, Lennon VA, Aston PA , et al. Insights from LGI1 and CASPR2 potassium channel complex autoantibody subtyping. JAMA Neurol 2013; 70 (2) 229-234
    CrossrefPubMedGoogle Scholar
  • 91 Graus F, Vincent A, Pozo-Rosich P , et al. Anti-glial nuclear antibody: marker of lung cancer-related paraneoplastic neurological syndromes. J Neuroimmunol 2005; 165 (1–2) 166-171
    CrossrefPubMedGoogle Scholar
  • 92 Pittock SJ, Lucchinetti CF, Lennon VA. Anti-neuronal nuclear autoantibody type 2: paraneoplastic accompaniments. Ann Neurol 2003; 53 (5) 580-587
    CrossrefPubMedGoogle Scholar
  • 93 Chan KH, Vernino S, Lennon VA. ANNA-3 anti-neuronal nuclear antibody: marker of lung cancer-related autoimmunity. Ann Neurol 2001; 50 (3) 301-311
    CrossrefPubMedGoogle Scholar
  • 94 Pittock SJ, Yoshikawa H, Ahlskog JE , et al. Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal, and spinal cord dysfunction. Mayo Clin Proc 2006; 81 (9) 1207-1214
    CrossrefPubMedGoogle Scholar
  • 95 Ariño H, Höftberger R, Gresa-Arribas N , et al. Paraneoplastic neurological syndromes and glutamic acid decarboxylase antibodies. JAMA Neurol 2015; 72 (8) 874-881
    CrossrefPubMedGoogle Scholar
  • 96 Greenlee JE, Brashear HR. Antibodies to cerebellar Purkinje cells in patients with paraneoplastic cerebellar degeneration and ovarian carcinoma. Ann Neurol 1983; 14 (6) 609-613
    CrossrefPubMedGoogle Scholar
  • 97 Vernino S, Lennon VA. New Purkinje cell antibody (PCA-2): marker of lung cancer-related neurological autoimmunity. Ann Neurol 2000; 47 (3) 297-305
    CrossrefPubMedGoogle Scholar
  • 98 Adamus G, Ren G, Weleber RG. Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy. BMC Ophthalmol 2004; 4: 5
    CrossrefPubMedGoogle Scholar
  • 99 McKeon A, Lennon VA, LaChance DH, Klein CJ, Pittock SJ. Striational antibodies in a paraneoplastic context. Muscle Nerve 2013; 47 (4) 585-587
    CrossrefPubMedGoogle Scholar
  • 100 Bataller L, Wade DF, Graus F, Stacey HD, Rosenfeld MR, Dalmau J. Antibodies to Zic4 in paraneoplastic neurologic disorders and small-cell lung cancer. Neurology 2004; 62 (5) 778-782
    CrossrefPubMedGoogle Scholar
  • 101 McKeon A, Lennon VA, Lachance DH, Fealey RD, Pittock SJ. Ganglionic acetylcholine receptor autoantibody: oncological, neurological, and serological accompaniments. Arch Neurol 2009; 66 (6) 735-741
    CrossrefPubMedGoogle Scholar
  • 102 Voltz R, Carpentier AF, Rosenfeld MR, Posner JB, Dalmau J. P/Q-type voltage-gated calcium channel antibodies in paraneoplastic disorders of the central nervous system. Muscle Nerve 1999; 22 (1) 119-122
    CrossrefPubMedGoogle Scholar
  • 103 Motomura M, Lang B, Johnston I, Palace J, Vincent A, Newsom-Davis J. Incidence of serum anti-P/O-type and anti-N-type calcium channel autoantibodies in the Lambert-Eaton myasthenic syndrome. J Neurol Sci 1997; 147 (1) 35-42
    CrossrefPubMedGoogle Scholar
  • 104 Kokmen E, Smith GE, Petersen RC, Tangalos E, Ivnik RC. The short test of mental status. Correlations with standardized psychometric testing. Arch Neurol 1991; 48 (7) 725-728
    CrossrefPubMedGoogle Scholar