# Seronegative Autoimmune Encephalitis With Neuropsychiatric Presentation: A Case Report

**Authors:** Christian David Galindo, Lesmer Galindo Ruiz, Victor Hugo Agudelo, Natalia Mejia, Uriel Castro Diaz

PMC · DOI: 10.7759/cureus.104133 · Cureus · 2026-02-23

## TL;DR

This case report describes a 68-year-old woman with seronegative autoimmune encephalitis presenting with neuropsychiatric symptoms and highlights the importance of early immunotherapy despite negative antibody tests.

## Contribution

The paper contributes a detailed case of seronegative AE with neuropsychiatric features and emphasizes the role of functional neuroimaging in diagnosis.

## Key findings

- The patient showed marked clinical improvement after high-dose corticosteroid therapy.
- Functional neuroimaging revealed cerebral metabolic abnormalities consistent with inflammation.
- Diagnostic evaluation ruled out infectious, metabolic, and structural causes.

## Abstract

Seronegative autoimmune encephalitis (AE) is an immune-mediated inflammatory disorder of the central nervous system that presents with a broad spectrum of neuropsychiatric manifestations, including acute behavioral changes, cognitive dysfunction, catatonia, and altered levels of consciousness. The absence of identifiable neuronal autoantibodies in serum or cerebrospinal fluid contributes to diagnostic uncertainty, delayed treatment initiation, and increased morbidity. Given the potential reversibility of this condition, early recognition and prompt initiation of immunotherapy are critical to optimizing clinical outcomes. We report the case of a 68-year-old woman with probable seronegative AE who presented with subacute neuropsychiatric deterioration characterized by prominent psychiatric symptoms and catatonia. An extensive diagnostic evaluation, including cerebrospinal fluid analysis, comprehensive autoimmune antibody testing, and exclusion of infectious, metabolic, and structural etiologies, failed to identify an alternative diagnosis. Functional neuroimaging with 18F-fluorodeoxyglucose positron emission tomography revealed cerebral metabolic abnormalities supportive of an inflammatory encephalitic process. The patient demonstrated marked clinical improvement following early initiation of high-dose intravenous corticosteroid therapy. This case underscores the diagnostic complexity of seronegative AE when neuropsychiatric manifestations predominate and overlap with primary psychiatric disorders. It highlights the importance of maintaining a high index of clinical suspicion despite negative serological findings and supports the use of clinical diagnostic criteria and adjunctive functional neuroimaging to guide early immunotherapeutic intervention in suspected seronegative AE.

## Linked entities

- **Diseases:** autoimmune encephalitis (MONDO:0020640), catatonia (MONDO:0800105)

## Full-text entities

- **Genes:** LGI1 (leucine rich glioma inactivated 1) [NCBI Gene 9211] {aka ADLTE, ADPAEF, ADPEAF, DEE121, EPITEMPIN, EPT}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, DPYSL5 (dihydropyrimidinase like 5) [NCBI Gene 56896] {aka CRAM, CRMP-5, CRMP5, CV2, RTSC4, Ulip6}, DPP6 (dipeptidyl peptidase like 6) [NCBI Gene 1804] {aka DPL1, DPPX, MRD33, VF2}, CNTNAP2 (contactin associated protein 2) [NCBI Gene 26047] {aka AUTS15, CASPR2, CDFE, NRXN4, PTHSL1}, PNMA2 (PNMA family member 2) [NCBI Gene 10687] {aka MA2, MM2, RGAG2}, BMPER (BMP binding endothelial regulator) [NCBI Gene 168667] {aka CRIM3, CV-2, CV2}
- **Diseases:** encephalitis (MESH:D004660), psychosis (MESH:D011618), attentional deficits (MESH:D001289), inflammatory encephalitic (MESH:D011818), Neuropsychiatric (MESH:C000631768), ischemic lesions (MESH:D017202), pleocytosis (MESH:D007964), Catatonia (MESH:D002389), auditory hallucinations (MESH:D006212), hypermetabolism (MESH:C565498), hypothyroidism (MESH:D007037), hypertension (MESH:D006973), encephalopathy (MESH:D001927), consciousness (MESH:D003244), psychomotor retardation (MESH:D011596), mutism (MESH:D009155), rigidity (MESH:D009127), cognitive dysfunction (MESH:D003072), coma (MESH:D003128), impaired recent memory (MESH:D008569), catatonic syndrome (MESH:D012560), hypophonic and sparse speech (MESH:D013064), type II diabetes mellitus (MESH:D003924), infarction (MESH:D007238), behavioral disturbances (MESH:D001523), malignancy (MESH:D009369), uterine leiomyoma (OMIM:150699), infectious encephalitis (MESH:D000069544), neuroinflammation (MESH:D000090862), inflammatory (MESH:D007249), sinus bradycardia (MESH:D012804), metabolic disturbances (MESH:D024821), Epstein-Barr virus (MESH:D020031), dyslipidemia (MESH:D050171), Autoimmune encephalitis (MESH:D020274), cerebral metabolic abnormalities (MESH:D008659), seizures (MESH:D012640), ischemia (MESH:D007511), Neurological (MESH:D009461), paraneoplastic (MESH:D010257), aortic valve disease (MESH:D000082862), encephalitic (MESH:D010301), varicella-zoster virus (MESH:D000073618), intracranial hemorrhage (MESH:D020300), paranoid ideation (MESH:D001072), hemorrhage (MESH:D006470), prion disease (MESH:D017096), CMV (MESH:D003586), autoimmune (MESH:D001327), delirium (MESH:D003693), neuropsychiatric manifestations (MESH:D012877), disorientation (MESH:D003221), immune-mediated (MESH:C567355)
- **Chemicals:** lorazepam (MESH:D008140), rituximab (MESH:D000069283), 18F-fluorodeoxyglucose (MESH:D019788), glucose (MESH:D005947), prednisone (MESH:D011241), cyclophosphamide (MESH:D003520), methylprednisolone (MESH:D008775)
- **Species:** human gammaherpesvirus 4 (Epstein Barr virus, no rank) [taxon 10376], Homo sapiens (human, species) [taxon 9606], Human alphaherpesvirus 3 (Varicella-zoster virus, no rank) [taxon 10335]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12928538/full.md

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12928538/full.md

## References

18 references — full list in the complete paper: https://tomesphere.com/paper/PMC12928538/full.md

---
Source: https://tomesphere.com/paper/PMC12928538