Clinical Neuroradiology

, Volume 29, Issue 4, pp 623–630 | Cite as

Limbic Encephalitis in Patients with Epilepsy—is Quantitative MRI Diagnostic?

  • Arndt-Hendrik Schievelkamp
  • Alina Jurcoane
  • Theodor Rüber
  • Leon Ernst
  • Andreas Müller
  • Burkhard Mädler
  • Hans Heinz Schild
  • Elke HattingenEmail author
Original Article



Limbic encephalitis (LE) is an immune-related disease with limbic symptoms, variable and asymmetric magnetic resonance imaging (MRI) aspects and antibody profiles. This study investigated the diagnostic value of quantitative relaxation times T2 (qT2) and MRI signal intensities (SI) in LE.


The prospective 3T-MRI study included 39 epilepsy patients with initially suspected LE and 20 healthy controls. Values and asymmetry indices of qT2, T2-weighted (T2-w) and proton density (PD)-w SI of manually delineated and automatically segmented amygdala and hippocampus were measured. Additionally, two raters made a blinded visual analysis on FLAIR (fluid attenuation inversion recovery) and T2-w images.


According to diagnostic guidelines, 22 patients had probable LE and 17 patients had possible LE. The qT2 was higher (p < 0.01) in patients than in controls (mean ± SD, amygdala 98 ± 7 ms vs. 90 ± 5 ms, hippocampus 101 ± 7 ms vs. 92 ± 3 ms), but was not different between probable and possible LE or between sides (left and right). The PD-w SI and T2-w SI were lower in patients than in controls but were not different between patient subgroups or between sides. Diagnostic performance of visual analysis was relatively poor.


Epilepsy patients with suspected LE had elevated qT2 in amygdala and hippocampus, whereas the expected T2-w SI increase was not found; however, the diagnostic value of qT2 remains questionable since it did not discriminate probable from possible LE.


Limbic encephalitis Amygdala Hippocampus T2-weighted MRI T2-relaxation time 



Fluid attenuation inversion recovery


Field of view


Limbic encephalitis


Laterality index


N-methyl-D-aspartate receptor


Proton density


Proton density weighted


Quantified T2-relaxation time


Region of interest


Signal intensity




Echo time


Repetition time


Voltage-gated potassium channel


Conflict of interest

A.-H. Schievelkamp, A. Jurcoane, T. Rüber, L. Ernst, A. Müller, B. Mädler, H.H. Schild, E. Hattingen and declare that they have no competing interests.


  1. 1.
    Kelley BP, Patel SC, Marin HL, Corrigan JJ, Mitsias PD, Griffith B. Autoimmune encephalitis: pathophysiology and imaging review of an overlooked diagnosis. AJNR Am J Neuroradiol. 2017;38:1070–8.CrossRefGoogle Scholar
  2. 2.
    da Rocha AJ, Nunes RH, Maia AC Jr, do Amaral LL. Recognizing autoimmune-mediated encephalitis in the differential diagnosis of limbic disorders. AJNR Am J Neuroradiol. 2015;36:2196–205.CrossRefGoogle Scholar
  3. 3.
    Bien CG, Deutsche Gesellschaft für Neurologie. S1-Leitlinie: Immunvermittelte Erkrankungen der grauen ZNS-Substanz sowie Neurosarkoidose. 2012. Accessed 31 Aug 2017.Google Scholar
  4. 4.
    Dalmau J, Rosenfeld MR. Autoimmune encephalitis update. Neuro Oncol. 2014;16:771-8.CrossRefGoogle Scholar
  5. 5.
    Graus F, Saiz A, Dalmau J. Antibodies and neuronal autoimmune disorders of the CNS. J Neurol. 2010;257:509–17.CrossRefGoogle Scholar
  6. 6.
    Bien CG, Vincent A, Barnett MH, Becker AJ, Blümcke I, Graus F, Jellinger KA, Reuss DE, Ribalta T, Schlegel J, Sutton I, Lassmann H, Bauer J. Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis. Brain. 2012;135:1622–38.CrossRefGoogle Scholar
  7. 7.
    Dalmau J, Bataller L. Clinical and immunological diversity of limbic encephalitis: a model for paraneoplastic neurologic disorders. Hematol Oncol Clin North Am. 2006;20:1319–35.CrossRefGoogle Scholar
  8. 8.
    Mittal MK, Rabinstein AA, Hocker SE, Pittock SJ, Wijdicks EF, McKeon A. Autoimmune encephalitis in the ICU: analysis of phenotypes, serologic findings, and outcomes. Neurocrit Care. 2016;24:240–50.CrossRefGoogle Scholar
  9. 9.
    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):1481–94.CrossRefGoogle Scholar
  10. 10.
    Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol. 2011;10:63–74.CrossRefGoogle Scholar
  11. 11.
    Vincent A. Autoimmune channelopathies: new antibody-mediated disorders of the central nervous system. F1000 Biol Rep. 2009;1:61.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Tüzün E, Dalmau J. Limbic encephalitis and variants: classification, diagnosis and treatment. Neurologist. 2007;13:261–71.CrossRefGoogle Scholar
  13. 13.
    Pittock SJ, Kryzer TJ, Lennon VA. Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol. 2004;56:715–9.CrossRefGoogle Scholar
  14. 14.
    Nunez-Enamorado N, Camacho-Salas A, Belda-Hofheinz S, Cordero-Castro C, Simon-De Las Heras R, Saiz-Diaz R, Martinez-Sarries FJ, Martinez-Menendez B, Graus F. Fast and spectacular clinical response to plasmapheresis in a paediatric case of anti-NMDA encephalitis. Rev Neurol. 2012;54:420–4.PubMedGoogle Scholar
  15. 15.
    Gresa-Arribas N, Titulaer MJ, Torrents A, Aguilar E, McCracken L, Leypoldt F, Gleichman AJ, Balice-Gordon R, Rosenfeld MR, Lynch D, Graus F, Dalmau J. Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol. 2014;13:167–77.CrossRefGoogle Scholar
  16. 16.
    Moscato EH, Jain A, Peng X, Hughes EG, Dalmau J, Balice-Gordon RJ. Mechanisms underlying autoimmune synaptic encephalitis leading to disorders of memory, behavior and cognition: insights from molecular, cellular and synaptic studies. Eur J Neurosci. 2010;32:298–309.CrossRefGoogle Scholar
  17. 17.
    Petit-Pedrol M, Armangue T, Peng X, Bataller L, Cellucci T, Davis R, McCracken L, Martinez-Hernandez E, Mason WP, Kruer MC, Ritacco DG, Grisold W, Meaney BF, Alcalá C, Sillevis-Smitt P, Titulaer MJ, Balice-Gordon R, Graus F, Dalmau J. 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.CrossRefGoogle Scholar
  18. 18.
    Leypoldt F, Wandinger K‑P, Bien CG, Dalmau J. Autoimmune encephalitis. Eur Neurol Rev. 2013;8:31–7.CrossRefGoogle Scholar
  19. 19.
    Titulaer MJ, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, Aguilar E, Gresa-Arribas N, Ryan-Florance N, Torrents A, Saiz A, Rosenfeld MR, Balice-Gordon R, Graus F, Dalmau J. 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.CrossRefGoogle Scholar
  20. 20.
    Urbach H, Soeder BM, Jeub M, Klockgether T, Meyer B, Bien CG. Serial MRI of limbic encephalitis. Neuroradiology. 2006;48:380–6.CrossRefGoogle Scholar
  21. 21.
    Wagner J, Witt J‑A, Helmstaedter C, Malter MP, Weber B, Elger CE. Automated volumetry of the mesiotemporal structures in antibody-associated limbic encephalitis. J Neurol Neurosurg Psychiatr. 2015;86:735–42.CrossRefGoogle Scholar
  22. 22.
    Wagner J, Schoene-Bake JC, Malter MP, Urbach H, Huppertz HJ, Elger CE, Weber B. Quantitative FLAIR analysis indicates predominant affection of the amygdala in antibody-associated limbic encephalitis. Epilepsia. 2013;54:1679–87.CrossRefGoogle Scholar
  23. 23.
    Irani SR, Bera K, Waters P, Zuliani L, Maxwell S, Zandi MS, Friese MA, Galea I, Kullmann DM, Beeson D, Lang B, Bien CG, Vincent A. N‑methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes. Brain. 2010;133:1655–67.CrossRefGoogle Scholar
  24. 24.
    Florance NR, Davis RL, Lam C, Szperka C, Zhou L, Ahmad S, Campen CJ, Moss H, Peter N, Gleichman AJ, Glaser CA, Lynch DR, Rosenfeld MR, Dalmau J. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol. 2009;66:11–8.CrossRefGoogle Scholar
  25. 25.
    Kotsenas AL, Watson RE, Pittock SJ, Britton JW, Hoye SL, Quek AM, Shin C, Klein CJ. MRI findings in autoimmune voltage-gated potassium channel complex encephalitis with seizures: one potential etiology for mesial temporal sclerosis. AJNR Am J Neuroradiol. 2014;35:84–9.CrossRefGoogle Scholar
  26. 26.
    Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, Cortese I, Dale RC, Gelfand JM, Geschwind M, Glaser CA, Honnorat J, Höftberger R, Iizuka T1, Irani SR, Lancaster E, Leypoldt F, Prüss H, Rae-Grant A, Reindl M, Rosenfeld MR, Rostásy K, Saiz A, Venkatesan A, Vincent A, Wandinger KP, Waters P, Dalmau J. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15:391–404.CrossRefGoogle Scholar
  27. 27.
    Essig M, Knopp MV, Schoenberg SO, Hawighorst H, Wenz F, Debus J, van Kaick G. Cerebral gliomas and metastases: assessment with contrast-enhanced fast fluid-attenuated inversion-recovery MR imaging. Radiology. 1999;210:551–7.CrossRefGoogle Scholar
  28. 28.
    Khan NL, Jeffree MA, Good C, Macleod W, Al-Sarraj S. Histopathology of VGKC antibody-associated limbic encephalitis. Neurology. 2009;72:1703–5.CrossRefGoogle Scholar
  29. 29.
    Kotsarini C, Griffiths PD, Wilkinson ID, Hoggard N. A systematic review of the literature on the effects of dexamethasone on the brain from in vivo human-based studies: implications for physiological brain imaging of patients with intracranial tumors. Neurosurgery. 2010;67:1799–815. discussion 1815.CrossRefGoogle Scholar
  30. 30.
    Cole AJ. Status epilepticus and periictal imaging. Epilepsia. 2004;45(Suppl 4):72–7.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Arndt-Hendrik Schievelkamp
    • 1
  • Alina Jurcoane
    • 1
  • Theodor Rüber
    • 2
  • Leon Ernst
    • 2
  • Andreas Müller
    • 1
  • Burkhard Mädler
    • 3
  • Hans Heinz Schild
    • 4
  • Elke Hattingen
    • 1
    Email author
  1. 1.Neuroradiology, Department of RadiologyUniversity Hospital BonnBonnGermany
  2. 2.Department of EpileptologyUniversity Hospital BonnBonnGermany
  3. 3.Philips GmbHUB HealthcareHamburgGermany
  4. 4.Department of RadiologyUniversity Hospital BonnBonnGermany

Personalised recommendations