Recurrent spatial disorientation and amnestic episodes associated with lung adenocarcinoma: a serum- and CSF-negative paraneoplastic case
Abstract
Recurrent seizure-like episodes with preserved motor function and negative conventional investigations pose a significant diagnostic challenge, particularly in elderly patients. We report an elderly patient presenting with recurrent, stereotyped episodes of spatial disorientation and amnesia. Extensive evaluation, including brain MRI, cerebrospinal fluid analysis, electroencephalography, serum tumor markers, and neuronal antibody testing, was unrevealing. The patient did not meet the 2016 criteria for possible autoimmune encephalitis. A previously monitored pulmonary nodule was surgically resected and confirmed as lung adenocarcinoma. Remarkably, neurological episodes completely resolved following tumor resection and did not recur after discontinuation of antiseizure medication during 10 months of follow-up. This case highlights a potential tumor-related seizure-associated network dysfunction in the absence of detectable antibodies or overt limbic inflammation. Careful tumor evaluation should be considered in similar diagnostic dilemmas, even when conventional autoimmune markers are negative.
##plugins.themes.bootstrap3.article.details##
spatial disorientation, amnesia, focal seizures, paraneoplastic neurological syndrome, lung adenocarcinoma, autoimmune epilepsy
2. Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016 Apr;15(4):391-404. doi: 10.1016/S1474-4422(15)00401-9. PMID: 26906964; PMCID: PMC5066574.
3. Van Steenhoven RW, de Vries JM, Bruijstens AL, et al. Mimics of Autoimmune Encephalitis: Validation of the 2016 Clinical Autoimmune Encephalitis Criteria. Neurol Neuroimmunol Neuroinflamm. 2023 Aug 15;10(6):e200148. doi: 10.1212/NXI.0000000000200148. Erratum in: Neurol Neuroimmunol Neuroinflamm. 2025 Jan;12(1):e200342. doi: 10.1212/NXI.0000000000200342. PMID: 37582614; PMCID: PMC10427145.
4. Flammer J, Neziraj T, Rüegg S, Pröbstel AK. Immune Mechanisms in Epileptogenesis: Update on Diagnosis and Treatment of Autoimmune Epilepsy Syndromes. Drugs. 2023 Feb;83(2):135-158. doi: 10.1007/s40265-022-01826-9. PMID: 36696027; PMCID: PMC9875200.
5. Pitsch J, van Loo KMJ, Gallus M, et al. CD8+ T-Lymphocyte-Driven Limbic Encephalitis Results in Temporal Lobe Epilepsy. Ann Neurol. 2021 Apr;89(4):666-685. doi: 10.1002/ana.26000. PMID: 33368582.
6. Marsili L, Marcucci S, LaPorta J, et al. Paraneoplastic Neurological Syndromes of the Central Nervous System: Pathophysiology, Diagnosis, and Treatment. Biomedicines. 2023 May 9;11(5):1406. doi: 10.3390/biomedicines11051406. PMID: 37239077; PMCID: PMC10216177.
7. Gallus M, Roll W, Dik A, et al. Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell-mediated limbic encephalitis. Sci Adv. 2023 Jun 9;9(23):eabq7595. doi: 10.1126/sciadv.abq7595. PMID: 37294768; PMCID: PMC10256169.
8. Ford H, Seery N, Tan T, et al. Indications and Diagnostic Yield of Paraneoplastic and Autoimmune Encephalitis Antibody Testing: A Retrospective Cohort Study. Brain Behav. 2025 Aug;15(8):e70779. doi: 10.1002/brb3.70779. PMID: 40847447; PMCID: PMC12373516.
9. Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014 Apr;55(4):475-82. doi: 10.1111/epi.12550. PMID: 24730690.
10. Guasp M, Dalmau J. Autoimmune Encephalitis. Med Clin North Am. 2025 Mar;109(2):443-461. doi: 10.1016/j.mcna.2024.09.001. PMID: 39893022.
11. Simonato M, Agoston DV, Brooks-Kayal A, et al. Identification of clinically relevant biomarkers of epileptogenesis - a strategic roadmap. Nat Rev Neurol. 2021 Apr;17(4):231-242. doi: 10.1038/s41582-021-00461-4. PMID: 33594276.
12. Schroeder C, Back C, Koc Ü, et al. Breakthrough treatment with bortezomib for a patient with anti-NMDAR encephalitis. Clin Neurol Neurosurg. 2018 Sep;172:24-26. doi: 10.1016/j.clineuro.2018.06.005. PMID: 29960102.
13. Scheibe F, Prüss H, Mengel AM, et al. Bortezomib for treatment of therapy-refractory anti-NMDA receptor encephalitis. Neurology. 2017 Jan 24;88(4):366-370. doi: 10.1212/WNL.0000000000003536. PMID: 28003505.
14. Kubota A, Tajima T, Narukawa S, et al. [Anti-Ma2, anti-NMDA-receptor and anti-GluRε2 limbic encephalitis with testicular seminoma: short-term memory disturbance]. Rinsho Shinkeigaku. 2012;52(9):666-71. Japanese. doi: 10.5692/clinicalneurol.52.666. PMID: 22989902.
15. Gultekin SH, Rosenfeld MR, Voltz R, et al. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain. 2000 Jul;123 ( Pt 7):1481-94. doi: 10.1093/brain/123.7.1481. PMID: 10869059.
16. Graus F, Escudero D, Oleaga L, et al. Syndrome and outcome of antibody-negative limbic encephalitis. Eur J Neurol. 2018 Aug;25(8):1011-1016. doi: 10.1111/ene.13661. Erratum in: Eur J Neurol. 2018 Oct;25(10):1303. doi: 10.1111/ene.13802. PMID: 29667271; PMCID: PMC6037545.
17. Bloch MH, Hwang WC, Baehring JM, Chambers SK. Paraneoplastic limbic encephalitis: ovarian cancer presenting as an amnesic syndrome. Obstet Gynecol. 2004 Nov;104(5 Pt 2):1174-7. doi: 10.1097/01.AOG.0000128110.31784.c8. PMID: 15516442.

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Archive of Clinical Cases is protected by copyright and may be used in accordance with copyright and other applicable laws. Content available at www.clinicalcases.eu and our digital applications is intended for personal noncommercial use.
Authors who submit a manuscript for publication in Archive of Clinical Cases agree to the following terms: a. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal. b. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal. c. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) only after the final version of the manuscript was accepted and published, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access). d. It is compulsory that before submission authors ensure that their work was not published in any other medical journals or pending acceptance for publication and that "Archives of Clinical Cases" is the only beneficiary at that moment if their work/case will be accepted by us.
Guidelines for linking to www.clinicalcases.eu a. The main purpose of the site linking to the Archive of Clinical Casess site should be educational. b. Links should be made to the Archive of Clinical Casess home page (www.clinicalcases.eu) or to the articles abstract. c. It is forbidden to use the Archive of Clinical Casess cover by outside organizations unless permission has been granted in advance, notifying our Secretary. d. Material owned by the Archive of Clinical Cases (including the name, logo, cover, and text) may not be used in any manner that may induce the idea or suggest that the Archive of Clinical Cases is in some way recommending a specific company, product or service. e. You must not use or allow others to access or use, all or any part of our Site or the contents and/or applications on it for commercial purposes without our permission. To seek permission to do anything prohibited by or not contained in these TERMS, or which requires our prior consent or agreement, you can contact us.
https://orcid.org/0000-0002-8285-5189