Abstract
Objective
To identify the clinical and radiological features that should raise suspicion for the autoimmune encephalitis (AE)-like presentation of glioblastoma.
Methods
This is an observational, retrospective case series of patients referred to the French National Reference Center on Paraneoplastic Neurological Diseases for suspected AE (possible, probable or definite, using the 2016 criteria) who later received a final diagnosis of glioblastoma according to 2016 WHO criteria. An extensive literature search was also conducted for similar existing cases.
Results
Between 2014 and 2016, 306 patients were referred to our center for suspected AE. Six of these patients (2%) later developed pathologically confirmed glioblastoma. Thirteen patients (9 male) were included for analysis (6 from the present series and 7 from the literature); median age was 63. Initially, a diagnosis of AE was clinically suspected based on: working memory deficits (77%), seizures (62%) (including status epilepticus in 23%), and psychiatric symptoms (46%). Initial brain MRI was not in favor of a typical glioblastoma pattern and showed bilateral (54%) or unilateral selective limbic involvement. Five patients exhibited initial slight contrast enhancement. A clear inflammatory CSF was present in five patients and three from the literature showed autoantibody positivity (NMDAR, VGKC, GluRepsilon2). Median delay between suspicions of AE to GBM diagnosis was 3 months (range 1.5–24) and one patient from the literature was diagnosed post-mortem.
Conclusions
An alternative diagnosis of glioblastoma should be considered in patients presenting initially as AE, especially in patients who do not fulfill the criteria for definite AE and in those with a poor clinical evolution despite initial improvement.
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References
Graus F, Titulaer MJ, Balu R et al (2016) A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 15(4):391–404
Omuro A, DeAngelis LM (2013) Glioblastoma and other malignant gliomas: a clinical review. JAMA 310(17):1842–1850
Rokutanda T, Inatomi Y, Yonehara T, Takahashi Y, Hirano T, Uchino M (2008) A case of glioblastoma misdiagnosed initially due to positive finding of anti-glutamate receptor antibody. Rinsho Shinkeigaku 48(7):497–500
Deramecourt V, Bombois S, Debette S et al (2009) Bilateral temporal glioma presenting as a paraneoplastic limbic encephalitis with pure cognitive impairment. Neurologist 15(4):208–211
Schulz UG, Thomas SR, Stewart W (2009) A difficult case solved at autopsy: memory loss, behavioural change and seizures. Pract Neurol 9(2):90–95
Nagata R, Ikeda K, Nakamura Y et al (2010) A case of gliomatosis cerebri mimicking limbic encephalitis: malignant transformation to glioblastoma. Intern Med 49(13):1307–1310
Nunes J, Carvalho S, Gouveia P et al (2012) Glioblastoma multiforme mimicking limbic encephalitis. Acta Med Port 25(Suppl 1):48–51
Fujii H, Kubo S, Yunoki T et al (2013) Glioblastoma with ovarian teratoma having N-methyl-D-aspartate receptor (NMDAR) antibody in CSF–a case report. Rinsho Shinkeigaku 53(9):712–715
Athauda D, Delamont RS, Pablo-Fernandez ED (2014) High grade glioma mimicking voltage gated potassium channel complex associated antibody limbic encephalitis. Case Rep Neurol Med 2014:458790
Lee WJ, Lee ST, Byun JI et al (2016) Rituximab treatment for autoimmune limbic encephalitis in an institutional cohort. Neurology 86(18):1683–1691
Kotsenas AL, Watson RE, Pittock SJ et al (2014) MRI findings in autoimmune voltage-gated potassium channel complex encephalitis with seizures: one potential etiology for mesial temporal sclerosis. AJNR Am J Neuroradiol 35(1):84–89
Malter MP, Widman G, Galldiks N et al (2016) Suspected new-onset autoimmune temporal lobe epilepsy with amygdala enlargement. Epilepsia 57(9):1485–1494
Do LD, Chanson E, Desestret V et al (2017) Characteristics in limbic encephalitis with anti-adenylate kinase 5 autoantibodies. Neurology 88(6):514–524
Milligan TA, Zamani A, Bromfield E (2009) Frequency and patterns of MRI abnormalities due to status epilepticus. Seizure 18(2):104–108
Kataoka H, Dalmau J, Taoka T, Ueno S (2009) Reduced N-acetylaspartate in the basal ganglia of a patient with anti-NMDA receptor encephalitis. Mov Disord 24(5):784–786
Brandão LA, Castillo M (2016) Adult brain tumors: clinical applications of magnetic resonance spectroscopy. Magn Reson Imaging Clin N Am 24(4):781–809
Reyes-Botero G, Dehais C, Idbaih A et al (2014) Contrast enhancement in 1p/19q-codeleted anaplastic oligodendrogliomas is associated with 9p loss, genomic instability, and angiogenic gene expression. Neuro Oncol 16(5):662–670
Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Dalmau J (2000) Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain 123(Pt 7):1481–1494
Frankel SA, German WJ (1958) Glioblastoma multiforme; review of 219 cases with regard to natural history, pathology, diagnostic methods, and treatment. J Neurosurg 15(5):489–503
Chu AB, Sever JL, Madden DL et al (1983) Oligoclonal IgG bands in cerebrospinal fluid in various neurological diseases. Ann Neurol 13(4):434–439
van Sonderen A, Schreurs MW, de Bruijn MA et al (2016) The relevance of VGKC positivity in the absence of LGI1 and Caspr2 antibodies. Neurology 86(18):1692–1699
Zandi MS, Paterson RW, Ellul MA et al (2015) Clinical relevance of serum antibodies to extracellular N-methyl-d-aspartate receptor epitopes. J Neurol Neurosurg Psychiatry 86(7):708–713
Acknowledgements
Data access, responsibility, and analysis: the corresponding author had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The abstract of the present study was presented as poster presentation at the European Academy of Neurology (EAN) Conference, Amsterdam, Nederland (24–27 June 2017).
Funding
Agence Nationale de la Recherche (ANR-14-CE15-0001-MECANO), the Fédération pour la recherche sur le cerveau (FRC-Neurodon2014) and CSL Behring France.
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Study concept and design: Vogrig, Honnorat. Acquisition of data: Vogrig, Joubert, Ducray, Thomas, Izquierdo, Decaestecker, Martinaud, Gerardin, Grand and Honnorat. Analysis and interpretation of data: Vogrig, Joubert, Ducray, Thomas, Izquierdo, Decaestecker, Martinaud, Gerardin, Grand and Honnorat. Drafting of the manuscript: Vogrig, Honnorat. Critical revision of the manuscript for important intellectual content: Vogrig, Joubert, Ducray, Thomas, Izquierdo, Decaestecker, Martinaud, Gerardin, Grand and Honnorat. Study supervision: Honnorat.
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Dr Vogrig reported receiving a fellowship grant from the European Academy of Neurology (EAN). No other disclosures were reported.
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All procedures were performed in accordance with the institutional ethics committee and the Declaration of Helsinki.
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Vogrig, A., Joubert, B., Ducray, F. et al. Glioblastoma as differential diagnosis of autoimmune encephalitis. J Neurol 265, 669–677 (2018). https://doi.org/10.1007/s00415-018-8767-1
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DOI: https://doi.org/10.1007/s00415-018-8767-1