, Volume 61, Issue 8, pp 853–860 | Cite as

Conventional brain MRI features distinguishing limbic encephalitis from mesial temporal glioma

  • Marco ZoccaratoEmail author
  • Silvia Valeggia
  • Luigi Zuliani
  • Matteo Gastaldi
  • Sara Mariotto
  • Diego Franciotta
  • Sergio Ferrari
  • Giuseppe Lombardi
  • Vittorina Zagonel
  • Piera De Gaspari
  • Mario Ermani
  • Alessio Signori
  • Anna Pichiecchio
  • Bruno Giometto
  • Renzo Manara
Diagnostic Neuroradiology



Radiological hallmark of autoimmune limbic encephalitis (LE) is a hyperintense signal in MRI T2-weighted images of mesial temporal structures. We aimed to identify conventional magnetic resonance imaging (MRI) features that can help distinguish LE from temporal glioma.


Brain MRIs of 25 patients affected by antibody-positive autoimmune LE, 24 patients affected by temporal glioma (tumor group), and 5 negative controls were retrospectively blindly evaluated in random order.


Ten brain MRIs from the LE group were correctly recognized; one additional patient with mesial temporal hyperintensity with anti-AK5 abs LE was wrongly diagnosed as having a tumor. The brain MRIs of the remaining 14 of the 25 patients with LE were judged negative or, in three cases, showed features not typical for LE. In the tumor group, all MRIs showed pathological alterations diagnosed as tumors in 22/24 cases and as LE in two (2/22, 9%). Unilateral lesions were more common in tumors than in neuroradiologically abnormal LE (96% vs. 18%, p < 0.001). T2/FLAIR hyperintensity of the parahippocampal gyrus was associated more with tumor than with LE (71% vs. 18%) (p = 0,009), as T2/FLAIR hyperintensity of extralimbic structures (p = 0.015), edema (p = 0.041), and mass effect (p = 0.015). Maintenance of gray/white matter distinction was strongly associated with LE (91% vs. 17%, p < 0.001).


Conventional brain MRI is a fundamental tool in the differential diagnosis between LE and glioma. Bilateral involvement and maintenance of gray/white matter distinction at the cortical/subcortical interface are highly suggestive of LE.


Limbic encephalitis Glioma Neuronal antibodies Brain MRI AK5 antibodies 



The authors thank Francesc Graus (Barcelona, Spain) for providing cell-based assay for AK5 antibody and Angela Vincent (Oxford, UK) for VGKC radioimmunoassay, and Joanne Fleming for reviewing the manuscript.


No funding was received for this study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

All procedures performed in the studies involving human participants were in accordance with the ethical standards of our institutional research committees and with the 1964 Helsinki Declaration and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Demaerel P, Van Dessel W, Van Paesschen W et al (2011) Autoimmune-mediated encephalitis. Neuroradiology 53:837–851. CrossRefGoogle Scholar
  2. 2.
    Graus F, Titulaer MJ, Balu R, et al (2016) A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 15:391–404.
  3. 3.
    Vogrig A, Joubert B, Ducray F, Thomas L, Izquierdo C, Decaestecker K, Martinaud O, Gerardin E, Grand S, Honnorat J (2018) Glioblastoma as differential diagnosis of autoimmune encephalitis. J Neurol 265:669–677. CrossRefGoogle Scholar
  4. 4.
    Hart IK, Waters C, Vincent A, Newland C, Beeson D, Pongs O, Morris C, Newsom-Davis J (1997) Autoantibodies detected to expressed K+ channels are implicated in neuromyotonia. Ann Neurol 41:238–246. CrossRefGoogle Scholar
  5. 5.
    Saiz A, Blanco Y, Sabater L, González F, Bataller L, Casamitjana R, Ramió-Torrentà L, Graus F (2008) Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain 131:2553–2563. CrossRefGoogle Scholar
  6. 6.
    Bernal F, Shams’ili S, Rojas I et al (2003) Anti-Tr antibodies as markers of paraneoplastic cerebellar degeneration and Hodgkin’s disease. Neurology. 60:230–234. CrossRefGoogle Scholar
  7. 7.
    van Sonderen A, Schreurs MWJ, de Bruijn MAAM, Boukhrissi S, Nagtzaam MMP, Hulsenboom ESP, Enting RH, Thijs RD, Wirtz PW, Sillevis Smitt PAE, Titulaer MJ (2016) The relevance of VGKC positivity in the absence of LGI1 and Caspr2 antibodies. Neurology 86:1692–1699. CrossRefGoogle Scholar
  8. 8.
    Louis DN, Ohgaki H, Wiestler ODCW (2016) World Health Organization histological classification of tumours of the central nervous system. International Agency for Research on Cancer, FranceGoogle Scholar
  9. 9.
    Athauda D, Delamont RS, De P-FE (2014) High grade glioma mimicking voltage gated potassium channel complex associated antibody limbic encephalitis. Case Rep Neurol Med 2014:1–4. Google Scholar
  10. 10.
    Cope TE, Breen DP, Chawda S, Cifelli A (2016) Anti-collapsin response mediator protein 5 encephalitis masquerading as a low-grade brain tumour. Pract Neurol 16:376–380. CrossRefGoogle Scholar
  11. 11.
    Deramecourt V, Bombois S, Debette S, Delbeuck X, Ramirez C, Reyns N, Kerdraon O, Maurage CA, Pasquier F (2009) Bilateral temporal glioma presenting as a paraneoplastic limbic encephalitis with pure cognitive impairment. Neurologist. 15:208–211. CrossRefGoogle Scholar
  12. 12.
    Kerling F, Blümcke I, Stefan H (2008) Pitfalls in diagnosing limbic encephalitis—a case report. Acta Neurol Scand 118:339–342CrossRefGoogle Scholar
  13. 13.
    Nagata R, Ikeda K, Nakamura Y, Ishikawa Y, Miura K, Sato R, Kawase Y, Kawabe K, Iwasaki Y (2010) A case of Gliomatosis Cerebri mimicking limbic encephalitis: malignant transformation to glioblastoma. Intern Med 49:1307–1310CrossRefGoogle Scholar
  14. 14.
    Simo M, Dalmau J (2009) Cerebral gliomatosis simulating limbic encephalitis. Neurologia 24:500–501Google Scholar
  15. 15.
    Schulz UG, Stewart W, Thomas SR (2009) A difficult case solved at autopsy: memory loss, behavioural change and seizures. Pract Neurol 9:90–95CrossRefGoogle Scholar
  16. 16.
    Urbach H, Soeder BM, Jeub M, Klockgether T, Meyer B, Bien CG (2006) Serial MRI of limbic encephalitis. Neuroradiology 48:380–386. CrossRefGoogle Scholar
  17. 17.
    Oyanguren B, Sánchez V, González FJ, de Felipe A, Esteban L, López-Sendón JL, Garcia-Barragán N, Martínez-San Millán J, Masjuán J, Corral I (2013) Limbic encephalitis: a clinical-radiological comparison between herpetic and autoimmune etiologies. Eur J Neurol 20:1566–1570. CrossRefGoogle Scholar
  18. 18.
    Kotsenas AL, Watson RE, Pittock SJ, Britton JW, Hoye SL, Quek AML, Shin C, Klein CJ (2014) MRI findings in autoimmune voltage-gated potassium channel complex encephalitis with seizures: one potential etiology for mesial temporal sclerosis. Am J Neuroradiol 35:84–89. CrossRefGoogle Scholar
  19. 19.
    Chourmouzi D, Papadopoulou E, Marias K, Drevelegas A (2014) Imaging of brain tumors. Surg Oncol Clin N Am 23:629–684. CrossRefGoogle Scholar
  20. 20.
    Dean BL, Drayer BP, Bird CR, Flom RA, Hodak JA, Coons SW, Carey RG (1990) Gliomas: classification with MR imaging. Radiology 174:411–415. CrossRefGoogle Scholar
  21. 21.
    Ng ASL, Kramer J, Centurion A, Dalmau J, Huang E, Cotter JA, Geschwind MD (2015) Clinico-pathological correlation in adenylate kinase 5 autoimmune limbic encephalitis. J Neuroimmunol 287:31–35. CrossRefGoogle Scholar
  22. 22.
    Tüzün E, Rossi JE, Karner SF, Centurion AF, Dalmau J (2007) Adenylate kinase 5 autoimmunity in treatment refractory limbic encephalitis. J Neuroimmunol 186:177–180. CrossRefGoogle Scholar
  23. 23.
    Do LD, Chanson E, Desestret V, Joubert B, Ducray F, Brugière S, Couté Y, Formaglio M, Rogemond V, Thomas-Antérion C, Borrega L, Laurens B, Tison F, Curot J, de Brouker T, Lebrun-Frenay C, Delattre JY, Antoine JC, Honnorat J (2017) Characteristics in limbic encephalitis with anti-adenylate kinase 5 autoantibodies. Neurology 88:514–524. CrossRefGoogle Scholar
  24. 24.
    Flanagan EP, Kotsenas AL, Britton JW, McKeon A, Watson RE, Klein CJ, Boeve BF, Lowe V, Ahlskog JE, Shin C, Boes CJ, Crum BA, Laughlin RS, Pittock SJ (2015) Basal ganglia T1 hyperintensity in LGI1-autoantibody faciobrachial dystonic seizures. Neurology 2.
  25. 25.
    Tripathi M, Tripathi M, Roy SG, Parida GK, Ihtisham K, Dash D, Damle N, Shamim SA, Bal C (2018) Metabolic topography of autoimmune non-paraneoplastic encephalitis. Neuroradiology 60:189–198. CrossRefGoogle Scholar
  26. 26.
    Urbach H, Rauer S, Mader I, Paus S, Wagner J, Malter MP, Prüss H, Lewerenz J, Kassubek J, Hegen H, Auer M, Deisenhammer F, Ufer F, Bien CG, Baumgartner A (2015) Supratentorial white matter blurring associated with voltage-gated potassium channel-complex limbic encephalitis. Neuroradiology 57:1203–1209. CrossRefGoogle Scholar
  27. 27.
    Kim JA, Chung J, Ho Yoon P et al (2001) Transient MR signal changes in patients with generalized tonicoclonic seizure or status epilepticus: Periictal diffusion-weighted imaging. Am J Neuroradiol 22:1149–1160Google Scholar
  28. 28.
    Gultekin SH, Rosenfeld MR, Voltz R et al (2000) Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain 123(Pt 7):1481–1494CrossRefGoogle Scholar
  29. 29.
    van Sonderen A, Thijs RD, Coenders EC, Jiskoot LC, Sanchez E, de Bruijn MAAM, van Coevorden-Hameete MH, Wirtz PW, Schreurs MWJ, Sillevis Smitt PAE, Titulaer MJ (2016) Anti-LGI1 encephalitis: clinical syndrome and long-term follow-up. Neurology 87:1449–1456. CrossRefGoogle Scholar
  30. 30.
    Finke C, Prüss H, Heine J, Reuter S, Kopp UA, Wegner F, Then Bergh F, Koch S, Jansen O, Münte T, Deuschl G, Ruprecht K, Stöcker W, Wandinger KP, Paul F, Bartsch T (2017) Evaluation of cognitive deficits and structural hippocampal damage in encephalitis with leucine-rich, glioma-inactivated 1 antibodies. JAMA Neurol 74:50–59. CrossRefGoogle Scholar
  31. 31.
    van Sonderen A, Ariño H, Petit-Pedrol M, Leypoldt F, Körtvélyessy P, Wandinger KP, Lancaster E, Wirtz PW, Schreurs MWJ, Sillevis Smitt PAE, Graus F, Dalmau J, Titulaer MJ (2016) The clinical spectrum of Caspr2 antibody-associated disease. Neurology 87:521–528. CrossRefGoogle Scholar
  32. 32.
    Hirai T, Korogi Y, Yoshizumi K, Shigematsu Y, Sugahara T, Takahashi M (2000) Limbic lobe of the human brain: evaluation with turbo fluid-attenuated inversion-recovery MR imaging. Radiology 215:470–475. CrossRefGoogle Scholar
  33. 33.
    Coan AC, Kubota B, Bergo FPG, Campos BM, Cendes F (2014) 3T MRI quantification of hippocampal volume and signal in mesial temporal lobe epilepsy improves detection of hippocampal sclerosis. Am J Neuroradiol 35:77–83. CrossRefGoogle Scholar
  34. 34.
    Wagner J, Schoene-Bake JC, Malter MP, Urbach H, Huppertz HJ, Elger CE, Weber B (2013) Quantitative FLAIR analysis indicates predominant affection of the amygdala in antibody-associated limbic encephalitis. Epilepsia 54:1679–1687. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Marco Zoccarato
    • 1
    • 2
    Email author
  • Silvia Valeggia
    • 1
  • Luigi Zuliani
    • 2
    • 3
  • Matteo Gastaldi
    • 4
  • Sara Mariotto
    • 5
  • Diego Franciotta
    • 4
  • Sergio Ferrari
    • 5
  • Giuseppe Lombardi
    • 6
  • Vittorina Zagonel
    • 6
  • Piera De Gaspari
    • 2
  • Mario Ermani
    • 7
  • Alessio Signori
    • 8
  • Anna Pichiecchio
    • 9
  • Bruno Giometto
    • 10
  • Renzo Manara
    • 11
  1. 1.Neurology UnitAULSS 6 EuganeaPaduaItaly
  2. 2.Neuroimmunology GroupIstituto di Ricerca PediatricaPaduaItaly
  3. 3.Department of NeurologyOspedale San BortoloVicenzaItaly
  4. 4.Neuroimmunology LaboratoryIRCSS Mondino FoundationPaviaItaly
  5. 5.Neurology Unit, Department of Neuroscience, Biomedicine and Movement SciencesUniversity of VeronaVeronaItaly
  6. 6.Department of Oncology, Oncology 1Veneto Institute of Oncology IOV-IRCCSPaduaItaly
  7. 7.Department of Neurosciences (DNS), Statistic and Informatics Unit, School of MedicineUniversity of PaduaPaduaItaly
  8. 8.Department of Health SciencesUniversity of GenoaGenoaItaly
  9. 9.Department of NeuroradiologyIRCSS Mondino FoundationPaviaItaly
  10. 10.Department of NeurologyOspedale Santa ChiaraTrentoItaly
  11. 11.Neuroradiology, Department of Medicine and Surgery, Sezione di NeuroscienzeUniversity of SalernoSalernoItaly

Personalised recommendations