Leucine-rich glioma-inactivated protein 1 antibody-positive limbic encephalitis in a patient with an early-stage asymptomatic breast cancer

Our plain-English summary of Leucine-rich glioma-inactivated protein 1 antibody-positive limbic encephalitis in a patient with an early-stage asymptomatic breast cancer, by M.F. Niño Uribe, G. Van Cutsem, P. Kerschen (BMJ Case Reports, 2025).

The study

• Authors: M.F. Niño Uribe, G. Van Cutsem, P. Kerschen
• Journal: BMJ Case Reports
• Published: 2025;18(4)
• Type of article: Case report
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Our patient is a woman who developed a subacute amnestic syndrome, followed by cognitive impairment, headache, temporal lobe epilepsy and hyponatraemia. An early-stage asymptomatic breast cancer was identified on positron emission tomography (PET) scan. After treatment with immunotherapy with high-dose corticosteroids, intravenous immunoglobulins, upfront rituximab and excision of the tumour, the patient gradually recovered. Partial retrograde and anterograde amnesia persisted during the initial weeks, followed by slow and steady improvement. Autoimmune encephalitis is a severe neurological disorder associated with antibodies against neuronal cell-surface or intracellular onconeural proteins. Anti-leucine-rich glioma inactivated 1 (LGI1) predominantly affects males in the seventh decade of life, and less than 10% of all cases are associated with cancer. Paraneoplastic cases have been associated with malignant thymoma, neuroendocrine tumours and mesothelioma and usually had Morvan syndrome, in which serum antibodies are more frequently directed against CASPR2 than against LGI1. We report the first well-documented case of anti-LGI1 limbic encephalitis in a woman with newly diagnosed breast cancer.

© BMJ Publishing Group Limited 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.

In plain English

This case report from Luxembourg described one previously healthy woman in her mid-40s who came to the emergency room with recent memory loss, 20 days after testing positive for COVID-19. Tests found anti-LGI1 antibodies in her blood (1/300) and, weakly, in her spinal fluid. MRI showed swelling of the left hippocampus and EEG showed a right temporal seizure. She was diagnosed with anti-LGI1 autoimmune limbic encephalitis. A PET scan showed a lesion in the right breast. It proved to be an early-stage breast carcinoma (stage pT2 N0) and was removed; none of the five sentinel lymph nodes examined showed metastasis. After immunoglobulins, high-dose corticosteroids and rituximab, she recovered gradually and returned to work at 80% of her previous time 12 months after discharge. The authors described this as, to their knowledge, the first well-documented case of this encephalitis with early-stage breast cancer. They stated that association is not causation, that the two conditions may have occurred together by chance, and that COVID-19 may have played a role. The article does not study asbestos. Mesothelioma is mentioned only from an earlier case series.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Case report (a single patient)
• Who was studied: One previously healthy white woman in her mid-40s, seen at the Neurology Department of the Centre Hospitalier de Luxembourg, with new anterograde amnesia
• Exposure: No asbestos or fiber exposure is studied or reported. The article concerns anti-LGI1 limbic encephalitis occurring together with breast cancer. The patient had a COVID-19 infection with mild respiratory symptoms 20 days before her emergency visit, a history of smoking and a family history of breast cancer.
• Main results:
  • In this patient, serum anti-voltage-gated potassium channel antibodies were elevated (739 pmol/L) and serum anti-LGI1 antibodies were positive (1/300). Anti-LGI1 in the spinal fluid was weakly positive and anti-CASPR2 was negative.
  • In this patient, brain MRI showed hyperintense signal and oedema in the left hippocampus.
  • In this patient, EEG on admission showed a focal seizure in the right temporal lobe.
  • In this patient, a whole-body PET scan found a lesion in the right breast. After lumpectomy, it was classified as infiltrative breast carcinoma, 30 mm along the long axis, at stage pT2 N0. None of the five right axillary sentinel lymph nodes examined showed metastasis (0/5).
  • The patient was treated with intravenous immunoglobulins, intravenous methylprednisolone 1 g per day for 5 days followed by tablets at 0.8 mg/kg/day for 1 month, and two rituximab 1000 mg infusions 2 weeks apart. She returned to work at 80% of her previous working time 12 months after discharge.
  • Using the PNS care score, the authors scored this case at 4, indicating a possible paraneoplastic neurological syndrome.
  • This is background the authors cited from an earlier published case series of anti-LGI1 encephalitis, not a finding of this case: malignancy was reported in 3 of 38 patients, one of them an abdominal mesothelioma.
• The authors' conclusion: The authors concluded that the case highlights a possible association between breast cancer and anti-LGI1 limbic encephalitis. They also concluded that, with awareness and rapid antibody testing, diagnosis and treatment can be started promptly.
• Limitations the authors state:
  • The authors stated that the limitations of case reports apply and that association is not causation.
  • The authors stated that the two disorders may have occurred at the same time by chance, because breast cancer is common, the patient has a family history of it, and anti-LGI1 encephalitis is rarely associated with cancer.
  • The authors noted that the patient's COVID-19 infection shortly before her symptoms may have played a role, either as a cause of post-infectious encephalitis or as a trigger.
  • The authors stated that LGI1 could not be detected in the tumour sample because no specific antibody is commercially available for this.

Topics

Medical terms in this study, explained in our Lexicon: Immunotherapy, Mesothelioma.

Related studies

• Evaluation of androgen receptor and GATA binding protein 3 as immunohistochemical markers in the diagnosis of metastatic breast carcinoma to the lung — Y. Hattori, A. Yoshida, et al. (2015)
• Methylthioadenosine Phosphorylase and Breast Cancer 1 Protein-Associated Protein 1 as Biomarkers for the Peritoneal Mesothelioma — Y. Chen, X. Du, et al. (2023)
• Anti-Ma2-Associated Limbic Encephalitis after Termination of Immune Checkpoint Inhibitor Therapy for Malignant Pleural Mesothelioma — R. Hashimoto, E. Tanabe, et al. (2021)
• p53 protein, EGF receptor, and anti-p53 antibodies in serum from patients with occupationally derived lung cancer — J. Schneider, P. Presek, et al. (1999)
• Induction of protein citrullination and auto-antibodies production in murine exposed to nickel nanomaterials — B.M. Mohamed, N.T. Boyle, et al. (2018)
• Metastases to the breast: differential diagnosis from primary breast carcinoma — B. Vergier, M. Trojani, et al. (1991)

Browse more research in BMJ Case Reports, or return to medical research.