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Positron Emission Tomography with 18F-Fluorodeoxyglucose Imaging Patterns in Autoimmune Encephalitis

  • PET/CT Imaging (R Morgado, Section Editor)
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Abstract

Purpose of Review

Autoimmune encephalitis (AE) is an underrecognized and potentially curable disease, which has been the focus of intense neurologic research. In the present manuscript, we review recent updates and the current role of brain positron emission tomography imaging with 18F-fluorodeoxyglucose (FDG-PET) in the detection of AE. We appraise the many metabolic imaging manifestations described in this disease, the role of PET-FDG in its diagnosis and follow-up, and the possible relationship between some patterns and specific autoantibodies. We also briefly discuss recently recognized imaging patterns and the potential impact of new technologies in recognition of such metabolic imaging appearances.

Recent Findings

AE findings on FDG-PET may have various patterns, but three are dominant and can be summarized as follows: (1) hypermetabolism in cortical areas, mainly in mesial temporal regions and less frequently in basal ganglia and higher cortical regions, is a common pattern in early stages of the disease. Such pattern is highly suggestive of limbic AE, since it has not been described in many other entities, except for brain tumors and active epileptic foci. (2) Also common is a reduced metabolism in the regions described above, which could happen both in the detection of the disease or in previous hypermetabolic areas which changed their pattern during the course of illness. (3) Other areas with hypometabolism can also occur, especially the “diffuse whole-brain cortical hypometabolism” manifestation, which is unspecific and can have degenerative diseases and other conditions as differential diagnoses. Some antibodies are more related to specific metabolic imaging patterns, but others do not correlate closely with imaging appearances.

Summary

We consider that FDG-PET imaging can aid in the early diagnosis of AE and may also be helpful while accessing the disease longitudinally while showing functional changes that occur after therapy. In both situations it can provide valuable information that is not provided by anatomic imaging alone.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. McKeon A. Autoimmune encephalopathies and dementias. Contin Lifelong Learn Neurol. 2016;22:538–58.

    Article  Google Scholar 

  2. • 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. Well-illustrated update on the state-of-the-art of FDG-PET and AE.

  3. Vollmer T, McCarthy M. Autoimmune encephalitis: a more treatable tragedy if diagnosed early. Neurology. 2016. doi:10.1212/WNL.0000000000002641.

    PubMed  Google Scholar 

  4. Sekigawa M, Okumura A, Niijima S, Hayashi M, Tanaka K, Shimizu T. Autoimmune focal encephalitis shows marked hypermetabolism on positron emission tomography. J Pediatr. 2010;156:158–60.

    Article  Google Scholar 

  5. Sinmaz N, Amatoury M, Merheb V, Ramanathan S, Dale R, Brilot F. Autoantibodies in movement and psychiatric disorders: updated concepts in detection methods, pathogenicity, and CNS entry. Ann NY Acad Sci. 2015;1351:22–38.

    Article  CAS  PubMed  Google Scholar 

  6. • Baumgartner A, Rauer S, Mader I, Meyer P. Cerebral FDG-PET and MRI findings in autoimmune limbic encephalitis: correlation with autoantibody types. J Neurol 2013;260:2744–53. One of the studies which tried to correlate imaging appearances with antibodies.

  7. Wingfield T, McHugh C, Vas A, Richardson A, Wilkins E, Bonington A, Varma A. Autoimmune encephalitis: a case series and comprehensive review of the literature. QJM. 2011;104:921–31.

    Article  CAS  PubMed  Google Scholar 

  8. Probasco J, Benavides D, Ciarallo A, Sanin B, Wabulya A, Bergey G, Kaplan P. Electroencephalographic and fluorodeoxyglucose-positron emission tomography correlates in anti-N-methyl-d-aspartate receptor autoimmune encephalitis. Epilepsy Behav Case Rep. 2014;2:174–78.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Höftberger R. Neuroimmunology: an expanding frontier in autoimmunity. Front Immunol. 2015;206:1–6.

    Google Scholar 

  10. Geschwind M. Rapidly progressive dementia. Contin Lifelong Learn Neurol. 2010;16:31–56.

    Article  Google Scholar 

  11. McEvoy LK, Fennema-Notestine C, Roddey JC. Alzheimer disease: quantitative structural neuroimaging for detection and prediction of clinical and structural changes in mild cognitive impairment 1 [Internet]. Radiology. 2009. doi:10.1148/radiol.2511080924.

    PubMed  PubMed Central  Google Scholar 

  12. Fisher R, Patel N, Lai E, Schulz P. Two different 18F-FDG brain PET metabolic patterns in autoimmune limbic encephalitis. Clin Nucl Med. 2012;37:e213–8.

    Article  PubMed  Google Scholar 

  13. Yakushev I, Hammers A, Fellgiebel A, Schmidtmann I, Scheurich A, Buchholz H-G, Peters J, Bartenstein P, Lieb K, Schreckenberger M. SPM-based count normalization provides excellent discrimination of mild Alzheimer’s disease and amnestic mild cognitive impairment from healthy aging. Neuroimage. 2008;44:43–50.

    Article  PubMed  Google Scholar 

  14. Catana C, Guimaraes A, Rosen B. PET and MR imaging: the odd couple or a match made in heaven? J Nucl Med. 2013;54:815–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Catana C, Drzezga A, Heiss D, Rosen B. PET/MRI for neurologic applications. J Nucl Med. 2012;53:1916–25.

    Article  PubMed  Google Scholar 

  16. Scheid R, Lincke T, Voltz R, Cramon D, Sabri O. Serial 18F-fluoro-2-deoxy-d-glucose positron emission tomography and magnetic resonance imaging of paraneoplastic limbic encephalitis. Arch Neurol Chic. 2004;61:1785–9.

    Article  Google Scholar 

  17. Leypoldt F, Buchert R, Kleiter I, Marienhagen J, Gelderblom M, Magnus T, Dalmau J, Gerloff C, Lewerenz J. Fluorodeoxyglucose positron emission tomography in anti-N-methyl-d-aspartate receptor encephalitis: distinct pattern of disease. J Neurol Neurosurg Psychiatry. 2012;83:681–6.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kumar A. NMDA receptor function during senescence: implication on cognitive performance. Front Neurosci. 2015;9:1–15.

    Google Scholar 

  19. Titulaer M, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T, Honig L, Benseler S, Kawachi I, Martinez-Hernandez E, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013;12:157–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Dalmau J, Gleichman A, Hughes E, Rossi J, Peng X, Lai M, Dessain S, Rosenfeld M, Balice-Gordon R, Lynch D. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 2008;7:1091–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Irani S, Michell A, Lang B, Pettingill P, Waters P, Johnson M, Schott J, Armstrong R, Zagami A, Bleasel A, et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol. 2011;69:892–900.

    Article  PubMed  Google Scholar 

  22. Dalmau J, Tüzün E, Wu H, Masjuan J, Rossi J, Voloschin A, Baehring J, Shimazaki H, Koide R, King D, et al. Paraneoplastic anti-N-methyl-d-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol. 2007;61:25–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ances B, Vitaliani R, Taylor R, Liebeskind D, Voloschin A, Houghton D, Galetta S, Dichter M, Alavi A, Rosenfeld M, et al. Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. Brain. 2005;128:1764–77.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Chanson J-B, Diaconu M, Honnorat J, Martin T, Seze J, Namer I-J, Hirsch E. PET follow-up in a case of anti-NMDAR encephalitis: arguments for cingulate limbic encephalitis. Epileptic Disord Int Epilepsy J Videotape. 2012;14:90–3.

    Google Scholar 

  25. Lee E, Kang J, Oh J, Kim J, Shin Y-W, Kim C-Y. 18F-fluorodeoxyglucose positron-emission tomography findings with anti-N-methyl-d-aspartate receptor encephalitis that showed variable degrees of catatonia: three cases report. J Epilepsy Res. 2014;4:69–73.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Wegner F, Wilke F, Raab P, Tayeb S, Boeck A-L, Haense C, Trebst C, Voss E, Schrader C, Logemann F, et al. Anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-d-aspartate receptor encephalitis show distinct patterns of brain glucose metabolism in 18F-fluoro-2-deoxy-d-glucose positron emission tomography. BMC Neurol. 2014;14:136.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Morooka M, Kubota K, Minamimoto R, Furuhata M, Abe T, Ito K, Okasaki M, Ishii K, Ishiwata K. 18F-FDG and 11C-methionine PET/CT findings in a case with anti-NMDA (NR2B) receptor encephalitis. Clin Nucl Med. 2012;37:400–2.

    Article  PubMed  Google Scholar 

  28. Greiner H, Leach J, Lee K-H, Krueger D. Anti-NMDA receptor encephalitis presenting with imaging findings and clinical features mimicking Rasmussen syndrome. Seizure. 2011;20:266–70.

    Article  PubMed  Google Scholar 

  29. Cistaro A, Caobelli F, Quartuccio N, Fania P, Pagani M. Uncommon 18F-FDG-PET/CT findings in patients affected by limbic encephalitis: hyper–hypometabolic pattern with double antibody positivity and migrating foci of hypermetabolism. Clin Imaging. 2015;39:329–33.

    Article  PubMed  Google Scholar 

  30. Tobin WO, Strand EA, Clark HM, Lowe VJ. NMDA receptor encephalitis causing reversible caudate changes on MRI and PET imaging. Neurol Clin Pract. 2014;4:470–73.

    Google Scholar 

  31. Yuan J, Guan H, Zhou X, Niu N, Li F, Cui L, Cui R. Changing brain metabolism patterns in patients with ANMDARE: serial 18F-FDG PET/CT findings. Clin Nucl Med. 2016;41:366–70.

    Article  PubMed  Google Scholar 

  32. Mohr B, Minoshima S. F-18 fluorodeoxyglucose PET/CT findings in a case of anti-NMDA receptor encephalitis. Clin Nucl Med. 2010;35:461–3.

    Article  PubMed  Google Scholar 

  33. Endres D, Perlov E, Stich O, Rauer S, Maier S, Waldkircher Z, Lange T, Mader I, Meyer P, Elst L. Hypoglutamatergic state is associated with reduced cerebral glucose metabolism in anti-NMDA receptor encephalitis: a case report. BMC Psychiatry. 2015;15:186.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Sonderen A, Schreurs M, Bruijn M, Boukhrissi S, Nagtzaam M, Hulsenboom E, Enting R, Thijs R, Wirtz P, Smitt P, et al. The relevance of VGKC positivity in the absence of LGI1 and Caspr2 antibodies. Neurology. 2016. doi:10.1212/WNL.0000000000002637.

    Google Scholar 

  35. Navarro V, Kas A, Apartis E, Chami L, Rogemond V, Levy P, Psimaras D, Habert M-O, Baulac M, Delattre J-Y, et al. Motor cortex and hippocampus are the two main cortical targets in LGI1-antibody encephalitis. Brain. 2016;139:1079–93.

    Article  PubMed  Google Scholar 

  36. Shin Y-W, Lee S-T, Shin J-W, Moon J, Lim J-A, Byun J-I, Kim T-J, Lee K-J, Kim Y-S, Park K-I, et al. VGKC-complex/LGI1-antibody encephalitis: clinical manifestations and response to immunotherapy. J Neuroimmunol. 2013;265:75–81.

    Article  CAS  PubMed  Google Scholar 

  37. Kamaleshwaran K, Iyer R, Antony J, Radhakrishnan E, Shinto A. 18F-FDG PET/CT findings in voltage-gated potassium channel limbic encephalitis. Clin Nucl Med. 2013;38:392–4.

    Article  PubMed  Google Scholar 

  38. Park S, Choi H, Cheon G, Kang K, Lee D. 18F-FDG PET/CT in anti-LGI1 encephalitis: initial and follow-up findings. Clin Nucl Med. 2015;40:156–8.

    Article  PubMed  Google Scholar 

  39. Lancaster E, Martinez-Hernandez E, Dalmau J. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology. 2011;77:179–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lai M, Hughes E, Peng X, Zhou L, Gleichman A, Shu H, Matà S, Kremens D, Vitaliani R, Geschwind M, et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol. 2009;65:424–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. • Spatola M, Stojanova V, Prior J, Dalmau J, Rossetti A. Serial brain 18FDG-PET in anti-AMPA receptor limbic encephalitis. J Neuroimmunol. 2014;271:53–55. Elegant investigation on anti-AMPA AE and prospective imaging.

  42. Wei Y-C, Liu C-H, Lin J-J, Lin K-J, Huang K-L, Lee T-H, Chang Y-J, Peng T-I, Lin K-L, Chang T-Y, et al. Rapid progression and brain atrophy in anti-AMPA receptor encephalitis. J Neuroimmunol. 2013;261:129–33.

    Article  CAS  PubMed  Google Scholar 

  43. Li X, Mao Y-T, Wu J-J, Li L-X, Chen X-J. Anti-AMPA receptor encephalitis associated with thymomatous myasthenia gravis. J Neuroimmunol. 2015;281:35–7.

    Article  CAS  PubMed  Google Scholar 

  44. Petit-Pedrol M, Armangue T, Peng X, Bataller L, Cellucci T, Davis R, McCracken L, Martinez-Hernandez E, Mason W, Kruer M, 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;13:276–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lancaster E, Lai M, Peng X, Hughes E, Constantinescu R, Raizer J, Friedman D, Skeen M, Grisold W, Kimura A, et al. Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen. Lancet Neurol. 2009;9:67–76.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Su M, Xu D, Tian R. 18F-FDG PET/CT and MRI findings in a patient with anti-GABAB receptor encephalitis. Clin Nucl Med. 2015;40:515–17.

    Article  PubMed  Google Scholar 

  47. Kim T-J, Lee S-T, Shin J-W, Moon J, Lim J-A, Byun J-I, Shin Y-W, Lee K-J, Jung K-H, Kim Y-S, et al. Clinical manifestations and outcomes of the treatment of patients with GABAB encephalitis. J Neuroimmunol. 2014;270:45–50.

    Article  CAS  PubMed  Google Scholar 

  48. • Lancaster E, Dalmau J. Neuronal autoantigens—pathogenesis, associated disorders and antibody testing. Nat Rev Neurol. 2012;8:380–90. Concise and easy to read review on clinical AE pathogenesis.

  49. Saiz A, Blanco Y, Sabater L, González F, Bataller L, Casamitjana R, Ramió-Torrentà L, Graus F. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain. 2008;131:2553–63.

    Article  PubMed  Google Scholar 

  50. Graus F, Saiz A, Dalmau J. Antibodies and neuronal autoimmune disorders of the CNS. J Neurol. 2010;257:509–17.

    Article  CAS  PubMed  Google Scholar 

  51. Bien C, Vincent A, Barnett M, Becker A, Blümcke I, Graus F, Jellinger K, Reuss D, Ribalta T, Schlegel J, et al. Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis. Brain. 2012;135:1622–38.

    Article  PubMed  Google Scholar 

  52. Ariño H, Gresa-Arribas N, Blanco Y, Martínez-Hernández E, Sabater L, Petit-Pedrol M, Rouco I, Bataller L, Dalmau J, Saiz A, et al. Cerebellar ataxia and glutamic acid decarboxylase antibodies: immunologic profile and long-term effect of immunotherapy. JAMA Neurol. 2014;71:1009–16.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Rakocevic G, Raju R, Dalakas M. Anti-glutamic acid decarboxylase antibodies in the serum and cerebrospinal fluid of patients with stiff-person syndrome: correlation with clinical severity. Arch Neurol Chic. 2004;61:902–4.

    Article  Google Scholar 

  54. Kojima G, Inaba M, Bruno M. PET-positive extralimbic presentation of anti-glutamic acid decarboxylase antibody-associated encephalitis. Epileptic Disord. 2014;16:358–61.

    PubMed  Google Scholar 

  55. Malter M, Helmstaedter C, Urbach H, Vincent A, Bien C. Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis. Ann Neurol. 2010;67:470–8.

    Article  PubMed  Google Scholar 

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Acknowledgments

We would like to thank Kimberly Stephens for her kind help with English language issues. AMNC would like to acknowledge the financial support of Sociedade Beneficente Hospital Sirio Libanes.

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Authors and Affiliations

  1. Department of Radiology, Centro de Medicina Nuclear (LIM 43), University of Sao Paulo Medical School, Travessa da Rua Ovídio Pires de Campos S/N, prédio do Centro de Medicina Nuclear, 2° andar, Cerqueira Cesar, Sao Paulo, CEP: 05403-010, Brazil

    Marianne Kimura Soriano, Carla Rachel Ono & Artur Martins Coutinho

  2. Nuclear Medicine and PET/CT Service, Hospital Sirio Libanes, Sao Paulo, Brazil

    Artur Martins Coutinho

  3. MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA

    Artur Martins Coutinho

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  1. Marianne Kimura Soriano
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Correspondence to Artur Martins Coutinho.

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Marianne Kimura Soriano, Carla Rachel Ono, and Artur M. N. Coutinho each declare no potential conflicts of interest.

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Soriano, M.K., Ono, C.R. & Coutinho, A.M. Positron Emission Tomography with 18F-Fluorodeoxyglucose Imaging Patterns in Autoimmune Encephalitis. Curr Radiol Rep 4, 47 (2016). https://doi.org/10.1007/s40134-016-0174-8

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