2026 ECNP Congress

PS02-2081

Seronegative limbic encephalitis with cytoplasmic antinuclear antibody positivity as a marker of paraneoplastic autoimmunity

Süleyman Alperen Daşcı — K.H. Cihan, H.C. Ereğli, E.İ. Tekeli, B. Duman, R.S. İlhan, K.C. Can, B. Çolak, Y. Kır, C.T. Işıkay, C. Yücesan, S. Erdoğan, R. Yılmaz, Ö.E. Yalap · Ankara University School of Medicine, Department of Psychiatry, Ankara, Türkiye

2026 ECNP Congress

Introduction

Autoimmune encephalitis comprises a group of paraneoplastic or immune-mediated syndromes presenting with subacute memory impairment, confusion and often seizures.Diagnosis is particularly challenging in seronegative cases, where no identifiable neuronal autoantibodies are detected despite a compatible clinical presentation.[1,2] We describe a patient with acute-onset confusion, memory deficits, visual hallucinations and behavioral changes in whom extensive work-up excluded infectious,vasculitic and malignant etiologies while MRI demonstrated limbic hyperintensities.Here,we report a case of seronegative limbic encephalitis with an atypical immunological finding of cytoplasmic ANA positivity in the CSF,raising questions about its potential role as a marker of paraneoplastic autoimmunity.

Case Presentation

A 69-year-old man with no prior psychiatric or neurological history and a medical history of psoriasis and diabetes mellitus,presented with a subacute onset of behavioral and cognitive disturbances, including subacute fatigue, sleep disturbance, visual hallucinations and prominent short-term memory impairment.On admission,the patient was confused (CAM-positive) with severe recent memory impairment (0/3 recall);catatonia was excluded using the Bush–Francis Catatonia Rating Scale and no meningeal signs were present.Physical examination was otherwise unremarkable except for pruritic lesions consistent with artefact dermatitis.MRI showed bilateral medial temporal hyperintensities involving the hippocampus and amygdala;EEG revealed mild diffuse abnormal slowing;CSF analysis was unremarkable with negative infectious studies.Empirical treatment with intravenous acyclovir, ceftriaxone, ampicillin, and vancomycin was initiated but discontinued due to lack of clinical improvement and negative infectious work-up. Infectious and rheumatologic etiologies were excluded, and vasculitis markers were negative. Given the patient’s advanced age and smoking history, a paraneoplastic autoimmune process was suspected. Contrast-enhanced CT and oncologic PET imaging showed no malignancy despite elevated CA 19-9 (65 U/mL).Autoimmune limbic encephalitis and paraneoplastic antibody panels were tested in both serum and CSF and were negative; the only abnormal finding was cytoplasmic ANA positivity in the CSF.Following a comprehensive work-up, seronegative autoimmune encephalitis was considered, and treatment with intravenous methylprednisolone (1000 mg/day for 10 days) followed by plasma exchange was initiated. Clinical improvement was observed, with resolution of confusion (CAM-negative) and improvement in short-term memory (0/3 to 1/3 recall). He was discharged on oral steroids but later died due to acute pneumonia.

Discussion

Seronegative autoimmune encephalitis is defined by the absence of detectable neuronal autoantibodies despite fulfilling clinical diagnostic criteria and represents a substantial proportion of cases.Our patient fulfilled criteria for possible autoimmune encephalitis (Graus et al., 2016)[1]. The combination of subacute neuropsychiatric symptoms, limbic MRI abnormalities,exclusion of alternative etiologies and response to immunotherapy strongly supports an autoimmune mechanism despite negative antibody panels.[3,4] Cytoplasmic ANA positivity in the CSF is an unusual finding.While it may reflect non-specific immune activation, it may also indicate an underlying autoimmune or paraneoplastic process not detected by current panels. Given the patient’s age, smoking history, and elevated CA 19-9 level, a paraneoplastic mechanism remains a relevant consideration.

Conclusions

This case highlights the diagnostic challenges of seronegative autoimmune encephalitis and the importance of clinical judgment in antibody-negative presentations.Early immunotherapy may result in clinical improvement.Cytoplasmic ANA positivity in the CSF may represent a non-specific immune marker or a potential clue to underlying paraneoplastic autoimmunity.

References

  1. Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391-404. doi:10.1016/S1474-4422(15)00401-9
  2. Graus F, Escudero D, Oleaga L, et al. Syndrome and outcome of antibody-negative limbic encephalitis. Eur J Neurol. 2018;25(8):1011-1016. doi:10.1111/ene.13661
  3. Irani SR, Vincent A. Autoimmune encephalitis – new awareness, challenging questions. Discov Med. 2011 May;11(60):449-58. PMID: 21616043.
  4. Dalmau J, Gleichman AJ, Hughes EG, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 2008;7(12):1091-1098. doi:10.1016/S1474-4422(08)70224-2