To characterize elevations in neurofilament light chain (NfL) and cerebrospinal fluid (CSF) oligoclonal bands (OCBs) as biomarkers of autoimmune encephalitis (AIE) in neuropsychiatric systemic lupus erythematosus (NPSLE).

Cognitive impairment is common among patients with systemic lupus erythematosus (SLE) and has numerous potential etiologies. Without reliable diagnostic biomarkers, it is difficult to ascertain which patients have NPSLE and may benefit from immunosuppression. We describe two patients with NPSLE manifesting as AIE with elevations in NfL (a marker of neuronal damage) and CSF-unique OCBs (markers of intrathecal immunoglobulin synthesis).

Patient 1: A 38-year-old woman with mixed connective tissue disease, SLE and antiphospholipid antibody syndrome presented with subacute working memory deficits, disorganized thinking and paranoia, followed by paresthesias and tremors.

Patient 2: A 37-year-old woman with SLE and a remote history of viral encephalitis (fully recovered) presented with several months of working memory deficits, mood changes, falls and abnormal facial movements.

In both cases, brain MRIs with contrast were unrevealing. EEGs were slow or normal. CSF white blood cells (WBCs) and protein were normal in Patient 1, but slightly elevated in Patient 2 (WBCs 6/uL, protein 75 mg/dL). Serum and CSF inflammatory, autoimmune and infectious studies were negative, except for positive CSF-unique OCBs – 7 in Patient 1 and 10 in Patient 2 – and markedly elevated NfL – 412 pg/mL in Patient 1 and 131 pg/mL in Patient 2 (normal ≤ 11.4 pg/mL). Both patients were diagnosed with NPSLE manifesting as AIE. They were treated with intravenous corticosteroids, intravenous immunoglobulin and steroid-sparing agents (cyclophosphamide for Patient 1 and rituximab for Patient 2) with marked improvement.

Elevated NfL and CSF-unique OCBs may distinguish inflammatory causes of cognitive impairment in patients with SLE and identify those with NPSLE, even when brain MRIs are negative. These exploratory findings merit further evaluation in larger series.