Limbic encephalitis is an inflammatory disorder of the limbic system that can be either paraneoplastic, often associated with malignancies and poor prognosis, or autoimmune, mediated by antibodies such as anti–N-methyl-D-aspartate receptor (anti-NMDAR) or anti–leucine-rich glioma-inactivated 1 (anti-LGI1) (1). Unlike paraneoplastic cases, autoimmune forms are less frequently cancer-related and generally respond well to immunotherapy (1) (2)

Diagnosis relies on clinical suspicion supported by neuroimaging, electroencephalography (EEG), cerebrospinal fluid (CSF) analysis, and detection of autoantibodies in serum or CSF (2). Autoimmune encephalitis often begins with nonspecific prodromal symptoms—including fever, malaise, and headache—followed by acute neurological manifestations such as seizures, confusion, and psychiatric disturbances. These neuropsychiatric symptoms are typically abrupt in onset and differ from primary psychiatric disorders (1), (3)

Anti-NMDAR encephalitis primarily affects children and young adults, with a mean age of 21 years and a strong female predominance (female-to-male ratio 4:1). Up to 58% of affected women have an associated ovarian teratoma (3). Brain MRI is normal in approximately 30% of cases, while EEG often demonstrates nonspecific diffuse slowing. CSF findings may range from mild lymphocytic pleocytosis to normal parameters. Confirmation of diagnosis is achieved by detection of anti-NMDAR antibodies, with CSF testing being more sensitive than serum (3).

Once autoimmune encephalitis is suspected, early tumor screening is crucial (4). Pelvic ultrasound, MRI, or whole-body CT can identify an ovarian teratoma, which is present in over half of adult women with anti-NMDAR encephalitis (2)

We report a challenging case of anti-NMDAR encephalitis associated with an ovarian immature teratoma, highlighting the diagnostic pitfalls, therapeutic strategy, and importance of early tumor detection.

Brain magnetic resonance imaging (MRI) showed no focal lesions or abnormalities on T2-weighted or FLAIR sequences. Cerebrospinal fluid (CSF) analysis demonstrated normal opening pressure, normal white blood cell count, and normal protein and glucose levels. Gram stain and bacterial cultures were negative. Electroencephalography (EEG) revealed diffuse background slowing without epileptiform discharges, consistent with an encephalopathic process. Empiric antimicrobial therapy was discontinued after infectious etiologies were excluded.

Given the absence of structural, metabolic, or infectious causes, autoimmune encephalitis was strongly suspected. CSF and serum samples were sent for autoimmune and paraneoplastic antibody panels, and tumor marker evaluation was initiated. Contrast-enhanced computed tomography (CT) of the abdomen and pelvis revealed a large right ovarian mass measuring 18 × 9.4 × 17.5 cm. The lesion was septated and cystic, containing areas of fat and calcification, radiologically suggestive of an ovarian teratoma.

High-dose intravenous methylprednisolone (1 g daily for 5 consecutive days) was initiated on hospital day 3. Due to minimal clinical improvement, therapeutic plasmapheresis was commenced on day 10. During her hospital course, the patient developed episodes of severe agitation and autonomic instability and required short-term endotracheal intubation for airway protection.

Behavioral symptoms were managed with short-term antipsychotic therapy, including haloperidol (administered for 2 days), risperidone (1 mg twice daily), quetiapine (200 mg twice daily), and clonazepam (1 mg three times daily). These agents were gradually tapered as her mental status improved.

In view of the ovarian mass, the patient underwent a right salpingo-oophorectomy. Histopathological examination confirmed an immature ovarian teratoma (FIGO stage IA, grade II). Following multidisciplinary discussion, adjuvant chemotherapy with the EP regimen (etoposide and cisplatin) was initiated in accordance with oncology guidelines.

After tumor resection, the patient demonstrated gradual neurological improvement, including increased alertness, reduced agitation, and partial recovery of spontaneous speech. However, a transient clinical deterioration prompted resumption of plasmapheresis and initiation of rituximab therapy (375 mg/m², administered in two doses two weeks apart). This resulted in marked and rapid improvement in cognitive function, orientation, and language abilities.

Subsequently, CSF testing returned positive for anti–N-methyl-D-aspartate receptor (anti-NMDAR) antibodies, confirming the diagnosis of anti-NMDAR encephalitis. By the time of discharge, the patient was fully oriented, seizure-free, and independent in activities of daily living. At six-month follow-up, she remained neurologically stable without seizure recurrence or neuropsychiatric relapse.

Anti–N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder characterized by antibodies against the NR1 subunit of the NMDA receptor, leading to a constellation of neuropsychiatric symptoms, seizures, and autonomic dysfunction (2, 3). The disorder predominantly affects children and young adults, with a strong female predominance, and is frequently associated with ovarian teratomas (3, 5)

Our patient presented with the prototypical features of anti-NMDAR encephalitis, including acute-onset seizures, cognitive impairment, behavioral disturbances, and transient aphasia. However, diagnosis was challenging due to normal brain MRI and unremarkable cerebrospinal fluid (CSF) findings, highlighting a well-recognized limitation: imaging and routine CSF studies can be normal in a substantial proportion of cases. EEG revealed nonspecific diffuse slowing, consistent with previously reported patterns in autoimmune encephalitis(3)

The detection of a large right ovarian mass was crucial in establishing the paraneoplastic nature of her illness. Ovarian teratomas are identified in over half of adult women with anti-NMDAR encephalitis, most commonly as mature cystic teratomas (2(3). Our case was notable for an immature ovarian teratoma, a rare entity that may harbor a higher antigenic load due to the presence of primitive neural tissue; although ovarian teratomas are well-recognized triggers of anti-NMDA receptor encephalitis, the occurrence of this syndrome in association with an immature teratoma is uncommon, with only a few cases reported in the literature(6). potentially explaining the patient’s severe presentation and delayed response to first-line therapy (7)

Management of anti-NMDAR encephalitis relies on a combination of tumor removal and immunotherapy. In our patient, neurological recovery improved after removing the Teratoma supporting evidence that early tumor resection in anti‑NMDA receptor encephalitis helps patients recover faster and lowers the risk of relapse(4). Regarding to immunotherapy First-line therapy typically consists of corticosteroids, intravenous immunoglobulin, or plasma exchange (2),(3). In patients with incomplete response, second-line therapies such as rituximab or cyclophosphamide are recommended and are associated with improved outcomes and reduced relapse risk (2),(3). In our patient, escalation to rituximab as second-line therapy, following incomplete response to corticosteroids and plasmapheresis, was associated with rapid neurological recovery, consistent with multicenter data showing that rituximab effectively reduces relapse risk and prolongs time to first relapse in anti-NMDAR encephalitis(8). In our patient, initial corticosteroids and plasmapheresis produced modest improvement; however, escalation to rituximab following tumor resection resulted in dramatic neurological recovery, consistent with the current literature.

Prognosis is generally favorable when early tumor removal is combined with prompt immunotherapy, with approximately 80% of patients achieving substantial recovery (3),(7). Delayed diagnosis or failure to identify and remove the tumor is associated with poorer outcomes, prolonged hospitalization, and increased risk of relapse, which occurs in 12–25% of cases, particularly when immunotherapy is incomplete or the tumor remains unresected (3, 7). Our patient remained neurologically stable and seizure-free at six months follow-up, illustrating the importance of timely recognition, aggressive immunotherapy, and early tumor management.

This case underscores several key clinical lessons: the need for high clinical suspicion of autoimmune encephalitis despite normal imaging and CSF; the importance of comprehensive tumor screening in adult women presenting with new-onset neuropsychiatric symptoms; and the role of second-line immunotherapy in patients with severe or refractory disease. Additionally, it highlights that immature ovarian teratomas, though uncommon, can serve as a potent antigenic source, reinforcing the necessity of individualized, multidisciplinary management strategies.