¹Majeed Haider, ²Joe Devlin, ²Alwin Sebastian, ²Alexander Fraser, ²Fahd Adeeb, ²Kieran Murray

¹Salmaniya Medical Complex, ²Limerick University Hospital

Background(s): Diagnosis of neuropsychiatric manifestations of Systemic Lupus Erythematosus (SLE) remains challenging due to the nonspecific nature of the manifestations and inability of diagnostic modalities to differentiate neuropsychiatric lupus from other illnesses with similar presentations. We present a patient with acute encephalitis and a positive antinuclear antibody test then we raise the question of whether it was caused by SLE.

Method(s): A 33-year-old female with polycystic ovary syndrome was admitted with four-day history of sleep disturbance, anxiety, fatigue, and headache, a one-day history of confusion, behavioral changes, and a witnessed generalized tonic-clonic seizure. She was not on any medications and there was no history of illicit drug use. She is originally from Brazil but currently residing in Ireland for studying. On examination, she was febrile (38.5 C) and tachycardiac (118 sinus rhythm).  Glasgow Coma Scale (GCS) was 14/15 due to confusion. Neurological examination was otherwise normal. No other features to suggest an autoimmune connective tissue disease were detected upon physical examination.

Investigations are shown in Supplementary Appendix 1. Initial investigations revealed a leukocytosis with neutrophilia and mildly raised CRP at 13 mg/L. Lumbar puncture showed a cerebral spinal fluid (CSF) pleocytosis with monocyte predominance and normal protein.  Brain Computed Tomography and chest X-ray were unremarkable. SARS-CoV-2 PCR test was negative.

The impression was of an infectious encephalitis. She was commenced on ceftriaxone (was changed later to meropenem after patient’s deterioration), vancomycin, acyclovir and levetiracetam. On day 4 of admission, she became increasingly confused despite being free of seizures and her level of consciousness deteriorated reaching a GCS of 3/15 requiring elective intubation. Magnetic Resonance Imaging (MRI) of the brain and echocardiography were both unremarkable. Electroencephalogram (EEG) showed diffuse slowing consistent with a non-specific encephalopathy. blood cultures, urinalysis, chest X-ray and CSF examinations for different pathogens did not reveal any infectious etiology including mycobacterium tuberculosis. Antinuclear antibody (ANA), however, was 1:1600 speckled pattern (normal below 1:200) with negative extractible nuclear antigen panel including dsDNA and normal complement level.

Given the fact that her ANA came back positive, further history was obtained from the patient’s partner to entertain the possibility of neuropsychiatric lupus. He reported that the patient was complaining occasionally from excessive hair loss and fatigue. He also mentioned remembering complains of occasional joints pain and rash when he was questioned about them. All the previous complains were not documented before in the patient’s medical record while being in Ireland. Previous blood tests which were done in Brazil when the patient was a teenager had reportedly shown positive ANA and patient was informed about the possibility of having SLE, but she had not required any treatment.

Despite the lack of specific findings of SLE, neuropsychiatric lupus was considered based on the history given by the patient’s partner, positive ANA and given the patient’s deterioration despite broad antimicrobial coverage for 7 days. Therefore, she was started on 1g pulsed IV methylprednisolone for 3 days followed by oral prednisolone 1mg/kg, intravenous immunoglobulins (IVIG) and cyclophosphamide which were all given on the 8th day of admission.

Subsequent investigations from CSF that were sent abroad for autoimmune encephalitis antibodies came back showing a positive Anti-NMDA receptor antibody. Accordingly, a full body computed tomography was requested and it showed a 3 cm left-sided cystic ovarian lesion with features suggestive of ovarian teratoma (Figure 1). On day 21 of admission a surgical resection of the detected mass was done, and histopathology report confirmed ovarian teratoma (Figure 2). Therefore, a final diagnosis was given as anti-NMDA Receptor Encephalitis secondary to ovarian teratoma. She was treated with five sessions of plasmapheresis and rituximab therapy which resulted in gradual but very slow recovery.

Result(s): Initial investigations did not lead to a certain diagnosis. However, the possibility of neuropsychiatric lupus was raised after ANA test requested by the neurologist came back positive  with a titer of 1:1600 speckled pattern (normal up to 1:200). Accordingly, the rheumatologist was consulted for the possibility of neuropsychiatric lupus. A final decision was made after a thorough discussion to manage the patient as a case of SLE with neuropsychiatric lupus. However, subsequent investigations changed the diagnosis to anti-NMDA Receptor Encephalitis secondary to ovarian teratoma.

Conclusion(s): This case highlights the importance of maintaining a broad differential for patients with encephalitis in possible cases of neuropsychiatric lupus. It also illustrates the importance of interpreting a positive ANA in its clinical context.