Abstract
Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious condition with varied manifestations of systemic lupus erythematosus (SLE) that involves the central and peripheral nervous systems. While seizures and psychiatric components are common findings, brain atrophy is not frequently reported, especially in young individuals. We present a case of a 22-year-old Saudi female who presented with a generalized tonic-clonic seizure and a significant history of undiagnosed psychiatric suffering. Neuroimaging of the brain demonstrated cortical atrophy and extensive subcortical hyperintensities. Autoimmune serology revealed SLE with the positivity of anti-dsDNA and anticardiolipin antibodies. The patient was diagnosed with NPSLE and treated with corticosteroids, hydroxychloroquine, and rituximab. A one-year follow-up MRI showed radiological stability with no new lesions or progression of atrophy. Clinically, she achieved complete seizure remission and improved neurocognitive function. We performed a structured literature review following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Databases were searched, including PubMed, Google Scholar, Springer, and Web of Science, for publications between 2013 and 2025. A total of 1,770 results were screened, and 20 studies were included in the review. The literature review and the case that is discussed support the link between neuroinflammation, injury mediated by autoantibodies, and structural brain changes in NPSLE. Seizures are regularly observed; cortical atrophy is atypical but could represent significant, long-term damage, especially among adults. Immunosuppressive therapy with rituximab can help stabilize both radiological findings and clinically significant manifestations of the disease. This report highlights the necessity of early recognition of neuropsychiatric symptoms in young individuals with an undiagnosed SLE. If an MRI shows central nervous system (CNS) atrophy, then aggressive immunosuppressive therapy is warranted despite the rare nature of findings during clinical presentation. Longitudinal imaging combined with multidisciplinary care may be particularly appropriate, as coordination among the neurologist, rheumatologist, and primary care physician is essential to achieving favorable outcomes in NPSLE.