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Transient epileptic amnesia: a retrospective cohort study of 127 cases, including CSF amyloid and tau features

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Abstract

Background

Transient epileptic amnesia (TEA) is a late-onset epilepsy syndrome encompassing transient iterative amnesias and interictal cognitive impairment, two features that overlap with incipient neurodegenerative dementias. We, therefore, examined the yield of CSF amyloid and tau biomarkers in TEA.

Methods

In this retrospective study, 127 TEA patients with unremarkable imaging findings were divided into 2 groups, namely, CSF (n = 71) and no-CSF (n = 56). Both were compared for demographics; medical history; baseline neurological, cognitive, and behavioral features; baseline mesial temporal lobe atrophy; and cognitive follow-up at a median of 13 months. CSF samples were examined for amyloid β-42 peptide as well as phospho-tau and total-tau levels.

Results

At baseline, the CSF-TEA group had significantly (p < 0.01) more frequent mild parkinsonism (42.9% vs. 20%) and cognitive concerns (31% vs. 10.7%), a more blunted sense of smell (34.3% vs. 9.4%), a lower baseline MMSE score (27 vs. 28.9), a more frequent amnestic mild cognitive impairment profile (69% vs. 42.6%), and more atrophic hippocampal changes. At follow-up, the CSF-TEA group had significantly (p < 0.01) lower MMSE scores (27.8 vs. 28.9). CSF analyses revealed amyloid and/or tau changes in 27 patients (38%), including an Alzheimer’s disease (AD) profile in 17 (24%).

Conclusions

This study shows a good diagnostic value of CSF sampling in a specific population of TEA with characteristics suggestive of incipient degenerative diseases (i.e., red flags). It argues for TEA being the inaugurating feature in some cases of AD. More broadly, our results suggest an etiological heterogeneity in TEA.

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Data availability

Data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Zeman AZ, Boniface SJ, Hodges JR (1998) Transient epileptic amnesia: a description of the clinical and neuropsychological features in 10 cases and a review of the literature. J Neurol Neurosurg Psychiatry 64(4):435–443. https://doi.org/10.1136/jnnp.64.4.435.PMID:9576532;PMCID:PMC2170058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Butler CR, Graham KS, Hodges JR, Kapur N, Wardlaw JM, Zeman AZ (2007) The syndrome of transient epileptic amnesia. Ann Neurol 61(6):587–598. https://doi.org/10.1002/ana.21111

    Article  PubMed  Google Scholar 

  3. Mosbah A, Tramoni E, Guedj E, Aubert S, Daquin G, Ceccaldi M, Félician O, Bartolomei F (2014) Clinical, neuropsychological, and metabolic characteristics of transient epileptic amnesia syndrome. Epilepsia 55(5):699–706. https://doi.org/10.1111/epi.12565

    Article  PubMed  Google Scholar 

  4. Blain A, Sellal F, Philippi N, Blanc F, Cretin B (2021) Transient epileptic amnesia is significantly associated with discrete CA1-located hippocampal calcifications but not with atrophic changes on brain imaging. Epilepsy Res 176:106736. https://doi.org/10.1016/j.eplepsyres.2021.106736

    Article  CAS  PubMed  Google Scholar 

  5. Savage SA, Butler CR, Hodges JR, Zeman AZ (2016) Transient epileptic amnesia over twenty years: long-term follow-up of a case series with three detailed reports. Seizure 43:48–55. https://doi.org/10.1016/j.seizure.2016.10.022

    Article  PubMed  PubMed Central  Google Scholar 

  6. Savage SA, Baker J, Milton F, Butler C, Zeman A (2022) Clinical outcomes in transient epileptic amnesia: a 10-year follow-up cohort study of 47 cases. Epilepsia 63(5):1115–1129. https://doi.org/10.1111/epi.17214

    Article  PubMed  PubMed Central  Google Scholar 

  7. Vossel KA, Tartaglia MC, Nygaard HB, Zeman AZ, Miller BL (2017) Epileptic activity in Alzheimer’s disease: causes and clinical relevance. Lancet Neurol 16(4):311–322. https://doi.org/10.1016/S1474-4422(17)30044-3.PMID:28327340;PMCID:PMC5973551

    Article  PubMed  PubMed Central  Google Scholar 

  8. Cretin B, Sellal F, Philippi N, Bousiges O, Di Bitonto L, Martin-Hunyadi C, Blanc F (2016) Epileptic prodromal Alzheimer’s disease, a retrospective study of 13 new cases: expanding the spectrum of Alzheimer’s disease to an epileptic variant? J Alzheimers Dis 52(3):1125–1133. https://doi.org/10.3233/JAD-150096

    Article  PubMed  Google Scholar 

  9. Ramanan VK, Morris KA, Graff-Radford J, Jones DT, Burkholder DB, Britton JW, Josephs KA, Boeve BF, Savica R (2019) Transient epileptic amnesia: a treatable cause of spells associated with persistent cognitive symptoms. Front Neurol 28(10):939. https://doi.org/10.3389/fneur.2019.00939

    Article  Google Scholar 

  10. Baker J, Savage S, Milton F, Butler C, Kapur N, Hodges J, Zeman A (2021) The syndrome of transient epileptic amnesia: a combined series of 115 cases and literature review. Brain Commun 3(2):fcab038. https://doi.org/10.1093/braincomms/fcab038

    Article  PubMed  PubMed Central  Google Scholar 

  11. Cretin B, Philippi N, Sellal F, Dibitonto L, Martin-Hunyadi C, Blanc F (2014) Can the syndrome of transient epileptic amnesia be the first feature of Alzheimer’s disease? Seizure 23(10):918–920. https://doi.org/10.1016/j.seizure.2014.07.008

    Article  PubMed  Google Scholar 

  12. Cretin B, Blanc F, Gaultier C, Sellal F (2012) Epileptic amnesic syndrome revealing Alzheimer’s disease. Epilepsy Res 102(3):206–209. https://doi.org/10.1016/j.eplepsyres.2012.08.002

    Article  PubMed  Google Scholar 

  13. Butler CR, Bhaduri A, Acosta-Cabronero J, Nestor PJ, Kapur N, Graham KS, Hodges JR, Zeman AZ (2009) Transient epileptic amnesia: regional brain atrophy and its relationship to memory deficits. Brain 132(Pt 2):357–368. https://doi.org/10.1093/brain/awn336

    Article  CAS  PubMed  Google Scholar 

  14. Visser PJ, Verhey F, Knol DL, Scheltens P, Wahlund LO, Freund-Levi Y, Tsolaki M, Minthon L, Wallin AK, Hampel H, Bürger K, Pirttila T, Soininen H, Rikkert MO, Verbeek MM, Spiru L, Blennow K (2009) Prevalence and prognostic value of CSF markers of Alzheimer’s disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: a prospective cohort study. Lancet Neurol 8(7):619–627. https://doi.org/10.1016/S1474-4422(09)70139-5

    Article  PubMed  Google Scholar 

  15. Romoli M, Sen A, Parnetti L, Calabresi P, Costa C (2021) Amyloid-β: a potential link between epilepsy and cognitive decline. Nat Rev Neurol 17(8):469–485. https://doi.org/10.1038/s41582-021-00505-9

    Article  CAS  PubMed  Google Scholar 

  16. Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL (1982) A new clinical scale for the staging of dementia. Br J Psychiatry 140:566–572. https://doi.org/10.1192/bjp.140.6.566

    Article  CAS  PubMed  Google Scholar 

  17. Thomas-Anterion C, Honore-Masson S, Laurent B (2006) The cognitive complaints interview. Psychogeriatrics 6:18–22

    Article  Google Scholar 

  18. Scheltens P, Leys D, Barkhof F, Huglo D, Weinstein HC, Vermersch P, Kuiper M, Steinling M, Wolters EC, Valk J (1992) Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry 55(10):967–972. https://doi.org/10.1136/jnnp.55.10.967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lanzone J, Ricci L, Assenza G, Ulivi M, Di Lazzaro V, Tombini M (2018) Transient epileptic and global amnesia: real-life differential diagnosis. Epilepsy Behav 88:205–211. https://doi.org/10.1016/j.yebeh.2018.07.015

    Article  PubMed  Google Scholar 

  20. Katsuyuki U, Masumi I, Masako W (2021) Epileptic cognitive impairment resembling Alzheimer’s disease: a new type of treatable neurocognitive disorder. Psychogeriatrics 21(4):686–688. https://doi.org/10.1111/psyg.12726

    Article  PubMed  Google Scholar 

  21. Butler CR (2006) Transient epileptic amnesia. Pract Neurol 6:368–371

    Article  Google Scholar 

  22. Cretin B, Bilger M, Philippi N, Blanc F (2020) CASPR2 antibody encephalitis presenting as transient epileptic amnesia. Seizure 81:175–177. https://doi.org/10.1016/j.seizure.2020.08.010

    Article  PubMed  Google Scholar 

  23. Del Felice A, Broggio E, Valbusa V, Gambina G, Arcaro C, Manganotti P (2014) Transient epileptic amnesia mistaken for mild cognitive impairment? A high-density EEG study. Epilepsy Behav 36:41–46. https://doi.org/10.1016/j.yebeh.2014.04.014

    Article  PubMed  Google Scholar 

  24. Striepens N, Scheef L, Wind A, Popp J, Spottke A, Cooper-Mahkorn D, Suliman H, Wagner M, Schild HH, Jessen F (2010) Volume loss of the medial temporal lobe structures in subjective memory impairment. Dement Geriatr Cogn Disord 29(1):75–81. https://doi.org/10.1159/000264630

    Article  PubMed  Google Scholar 

  25. Petersen RC, Parisi JE, Dickson DW, Johnson KA, Knopman DS, Boeve BF, Jicha GA, Ivnik RJ, Smith GE, Tangalos EG, Braak H, Kokmen E (2006) Neuropathologic features of amnestic mild cognitive impairment. Arch Neurol 63(5):665–672. https://doi.org/10.1001/archneur.63.5.665

    Article  PubMed  Google Scholar 

  26. Savage SA, Butler CR, Milton F, Han Y, Zeman AZ (2017) On the nose: Olfactory disturbances in patients with transient epileptic amnesia. Epilepsy Behav 66:113–119. https://doi.org/10.1016/j.yebeh.2016.09.043

    Article  PubMed  Google Scholar 

  27. Rabinowicz AL, Starkstein SE, Leiguarda RC, Coleman AE (2000) Transient epileptic amnesia in dementia: a treatable unrecognized cause of episodic amnestic wandering. Alzheimer Dis Assoc Disord 14(4):231–233. https://doi.org/10.1097/00002093-200010000-00008

    Article  CAS  PubMed  Google Scholar 

  28. Tsai ZR, Zhang HW, Tseng CH, Peng HC, Kok VC, Li GP, Hsiung CA, Hsu CY (2021) Late-onset epilepsy and subsequent increased risk of dementia. Aging (Albany NY) 13(3):3573–3587. https://doi.org/10.18632/aging.202299

    Article  PubMed  Google Scholar 

  29. Keret O, Hoang TD, Xia F, Rosen HJ, Yaffe K (2020) Association of late-onset unprovoked seizures of unknown etiology with the risk of developing dementia in older veterans. JAMA Neurol 77(6):710–715. https://doi.org/10.1001/jamaneurol.2020.0187.PMID:32150220;PMCID:PMC7063560

    Article  PubMed  Google Scholar 

  30. Kawakami O, Koike Y, Ando T, Sugiura M, Kato H, Hiraga K, Kito H, Kondo H (2018) Incidence of dementia in patients with adult-onset epilepsy of unknown causes. J Neurol Sci 15(395):71–76. https://doi.org/10.1016/j.jns.2018.09.010

    Article  Google Scholar 

  31. Tombini M, Assenza G, Ricci L, Lanzone J, Boscarino M, Vico C, Magliozzi A, Di Lazzaro V (2021) Temporal lobe epilepsy and Alzheimer’s disease: from preclinical to clinical evidence of a strong association. J Alzheimers Dis Rep 5(1):243–261. https://doi.org/10.3233/ADR-200286

    Article  PubMed  PubMed Central  Google Scholar 

  32. Alvarez MV, Evidente VG (2008) Understanding drug-induced parkinsonism: separating pearls from oy-sters. Neurology 70(8):e32–e34. https://doi.org/10.1212/01.wnl.0000302255.49113.51

    Article  PubMed  Google Scholar 

  33. Sarazin M, Berr C, De Rotrou J, Fabrigoule C, Pasquier F, Legrain S, Michel B, Puel M, Volteau M, Touchon J, Verny M, Dubois B (2007) Amnestic syndrome of the medial temporal type identifies prodromal AD: a longitudinal study. Neurology 69(19):1859–1867. https://doi.org/10.1212/01.wnl.0000279336.36610.f7.Erratum.In:Neurology.2008May20;70(21):2016

    Article  CAS  PubMed  Google Scholar 

  34. Barkhof F, Polvikoski TM, van Straaten EC, Kalaria RN, Sulkava R, Aronen HJ, Niinistö L, Rastas S, Oinas M, Scheltens P, Erkinjuntti T (2007) The significance of medial temporal lobe atrophy: a postmortem MRI study in the very old. Neurology 69(15):1521–1527. https://doi.org/10.1212/01.wnl.0000277459.83543.99

    Article  CAS  PubMed  Google Scholar 

  35. Cretin B, Philippi N, Bousiges O, Dibitonto L, Sellal F, Martin-Hunyadi C, Blanc F (2017) Do we know how to diagnose epilepsy early in Alzheimer’s disease? Rev Neurol (Paris) 173(6):374–380. https://doi.org/10.1016/j.neurol.2017.03.028

    Article  CAS  PubMed  Google Scholar 

  36. Jack CR Jr, Knopman DS, Chételat G, Dickson D, Fagan AM, Frisoni GB, Jagust W, Mormino EC, Petersen RC, Sperling RA, van der Flier WM, Villemagne VL, Visser PJ, Vos SJ (2016) Suspected non-Alzheimer disease pathophysiology: concept and controversy. Nat Rev Neurol 12(2):117–124. https://doi.org/10.1038/nrneurol.2015.251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ukai K, Watanabe M (2019) Transient epileptic amnesia accompanied by prodromal symptoms of dementia with Lewy bodies: the second case report in the literature. Psychogeriatrics 19(6):622–623. https://doi.org/10.1111/psyg.12434

    Article  PubMed  Google Scholar 

  38. Fouchard AA, Biberon J, Mondon K, de Toffol B (2016) Transient epileptic amnesia secondary to hippocampal dysplasia mimicking transient global amnesia. Seizure 43:23–25. https://doi.org/10.1016/j.seizure.2016.10.009

    Article  CAS  PubMed  Google Scholar 

  39. Savage SA, Irani SR, Leite MI, Zeman AZ (2019) NMDA receptor antibody encephalitis presenting as transient epileptic amnesia. J Neuroimmunol 327:41–43. https://doi.org/10.1016/j.jneuroim.2019.01.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Day GS, Yarbrough MY, Körtvelyessy P, Prüss H, Bucelli RC, Fritzler MJ, Mason W, Tang-Wai DF, Steriade C, Hébert J, Henson RL, Herries EM, Ladenson JH, Lopez-Chiriboga AS, Graff-Radford NR, Morris JC, Fagan A (2021) Prospective quantification of CSF biomarkers in antibody-mediated encephalitis. Neurology 96(20):e2546–e2557. https://doi.org/10.1212/WNL.0000000000011937

    Article  PubMed  PubMed Central  Google Scholar 

  41. Sarkis RA, Willment KC, Pennell PB, Marshall G (2019) Late-onset unexplained epilepsy: What are we missing? Epilepsy Behav 99:106478. https://doi.org/10.1016/j.yebeh.2019.106478

    Article  PubMed  Google Scholar 

  42. Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Feldman HH, Frisoni GB, Hampel H, Jagust WJ, Johnson KA, Knopman DS, Petersen RC, Scheltens P, Sperling RA, Dubois B (2016) A/T/N: an unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology 87(5):539–547. https://doi.org/10.1212/WNL.0000000000002923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to thank Dr. Véronique MUTSCHLER for her assistance in the reading and interpretation of standard EEG recordings, Prof. HIRSCH and Dr. VALENTI-HIRSCH for their help in the reading and interpretation of the video-EEG recordings, and Mrs. Isabella ATHANASSIOU for her assistance in English language editing.

Author information

Authors and Affiliations

  1. Centre Mémoire, de Ressources et de Recherche d’Alsace (Strasbourg-Colmar), Service de Neurologie des Hôpitaux Universitaires de Strasbourg, Pôle Tête et Cou, 1 Avenue Molière, 67200, Strasbourg, France

    Benjamin Cretin, Nathalie Philippi, Olivier Bousiges & Frédéric Blanc

  2. Unité de Neuropsychologie, Service de Neurologie et hôpital de jour de Gériatrie, pôle de Gériatrie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France

    Benjamin Cretin, Nathalie Philippi & Frédéric Blanc

  3. University of Strasbourg and CNRS, ICube laboratory UMR 7357 and FMTS (Fédération de Médecine Translationnelle de Strasbourg), Team IMIS/Neurocrypto Strasbourg, Strasbourg, France

    Benjamin Cretin, Nathalie Philippi & Frédéric Blanc

  4. Centre de Compétences des démences rares des Hôpitaux Universitaires de Strasbourg, Strasbourg, France

    Benjamin Cretin, Nathalie Philippi & Frédéric Blanc

  5. University Hospital of Strasbourg, Laboratory of Biochemistry and Molecular Biology, CNRS, Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR7364, Strasbourg, France

    Olivier Bousiges

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  1. Benjamin Cretin
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Contributions

BC contributed to the study design. BC, NP, OB, and FB contributed to the production of the main text of the manuscript. BC supervised the data acquisition and revised the manuscript. BC performed the statistical analysis.

Corresponding author

Correspondence to Benjamin Cretin.

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The authors declare that they have no conflicts of interest.

Ethical standard

All retrospective study procedures were performed following protocols approved by the Institutional Review Board (Direction de la Recherche Clinique et de l’Innovation) at our center. The study was conducted in accordance with the Declaration of Helsinki.

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Written informed consent was obtained from all research participants recruited.

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Cretin, B., Philippi, N., Bousiges, O. et al. Transient epileptic amnesia: a retrospective cohort study of 127 cases, including CSF amyloid and tau features. J Neurol 270, 2256–2270 (2023). https://doi.org/10.1007/s00415-023-11576-7

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  • DOI: https://doi.org/10.1007/s00415-023-11576-7

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