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

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Abbreviations

FLAIR:

Fluid attenuation inversion recovery

FOV:

Field of view

LE:

Limbic encephalitis

LI:

Laterality index

NMDA:

N-methyl-D-aspartate receptor

PD:

Proton density

PD-w:

Proton density weighted

qT2:

Quantified T2-relaxation time

ROI:

Region of interest

SI:

Signal intensity

T2-w:

T2-weighted

TE:

Echo time

TR:

Repetition time

VGKC:

Voltage-gated potassium channel

References

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  3. Bien CG, Deutsche Gesellschaft für Neurologie. S1-Leitlinie: Immunvermittelte Erkrankungen der grauen ZNS-Substanz sowie Neurosarkoidose. 2012. https://www.dgn.org/leitlinien/2396-ll-32-2012-immunvermittelte-erkrankungen-der-grauen-zns-substanz-sowie-neurosarkoidose. Accessed 31 Aug 2017.

    Google Scholar 

  4. Dalmau J, Rosenfeld MR. Autoimmune encephalitis update. Neuro Oncol. 2014;16:771-8.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  11. Vincent A. Autoimmune channelopathies: new antibody-mediated disorders of the central nervous system. F1000 Biol Rep. 2009;1:61.

    PubMed  PubMed Central  Google Scholar 

  12. Tüzün E, Dalmau J. Limbic encephalitis and variants: classification, diagnosis and treatment. Neurologist. 2007;13:261–71.

    Article  Google Scholar 

  13. Pittock SJ, Kryzer TJ, Lennon VA. Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol. 2004;56:715–9.

    Article  CAS  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  18. Leypoldt F, Wandinger K‑P, Bien CG, Dalmau J. Autoimmune encephalitis. Eur Neurol Rev. 2013;8:31–7.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  20. Urbach H, Soeder BM, Jeub M, Klockgether T, Meyer B, Bien CG. Serial MRI of limbic encephalitis. Neuroradiology. 2006;48:380–6.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  28. Khan NL, Jeffree MA, Good C, Macleod W, Al-Sarraj S. Histopathology of VGKC antibody-associated limbic encephalitis. Neurology. 2009;72:1703–5.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  30. Cole AJ. Status epilepticus and periictal imaging. Epilepsia. 2004;45(Suppl 4):72–7.

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Neuroradiology, Department of Radiology, University Hospital Bonn, Sigmund Freud Str. 25, 53127, Bonn, Germany

    Arndt-Hendrik Schievelkamp, Alina Jurcoane, Andreas Müller & Elke Hattingen

  2. Department of Epileptology, University Hospital Bonn, Bonn, Germany

    Theodor Rüber & Leon Ernst

  3. Philips GmbH, UB Healthcare, Lübeckertordamm 5, 20099, Hamburg, Germany

    Burkhard Mädler

  4. Department of Radiology, University Hospital Bonn, Sigmund Freud Str. 25, 53127, Bonn, Germany

    Hans Heinz Schild

Authors
  1. Arndt-Hendrik Schievelkamp
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  2. Alina Jurcoane
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  3. Theodor Rüber
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  4. Leon Ernst
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  8. Elke Hattingen
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Correspondence to Elke Hattingen.

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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.

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Schievelkamp, AH., Jurcoane, A., Rüber, T. et al. Limbic Encephalitis in Patients with Epilepsy—is Quantitative MRI Diagnostic?. Clin Neuroradiol 29, 623–630 (2019). https://doi.org/10.1007/s00062-018-0705-1

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  • DOI: https://doi.org/10.1007/s00062-018-0705-1

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