ARTHRITIS & RHEUMATISM Vol. 48, No. 10, October 2003, pp 2881–2887 DOI 10.1002/art.11279 © 2003, American College of Rheumatology Neuronal and Astrocytic Damage in Systemic Lupus Erythematosus Patients With Central Nervous System Involvement Estelle Trysberg, Karin Nylen, Lars E. Rosengren, and Andrej Tarkowski Objective. Symptoms originating from the central nervous system (CNS) frequently occur in patients with systemic lupus erythematosus (SLE). CNS involvement in lupus is associated with increased morbidity and mortality. Currently, reliable markers for activity in this condition are absent. The goal of this study was to determine the level of the light subunit of the neurofila- ment triplet protein (NFL) and that of glial fibrillary acidic protein (GFAP) in the cerebrospinal fluid of SLE patients with clinically verified CNS involvement and compare them with the levels in SLE patients without CNS involvement. Methods. We assessed cerebrospinal fluid ob- tained from 99 patients with SLE and 99 age-matched controls for the presence of soluble molecules indicating neuronal destruction and astrogliosis—NFL and GFAP, respectively. Patients were evaluated clinically, with magnetic resonance imaging (MRI) of the brain, cere- brospinal fluid analyses, and neuropsychiatric tests. Results. In the group of lupus patients with CNS involvement, intrathecal levels of NFL and GFAP were increased an average of 7-fold (P < 0.0001) and 3-fold (P < 0.05), respectively, compared with the levels in SLE patients without overt CNS disease. Intrathecal levels of NFL correlated significantly with cerebrospinal fluid levels of interleukin-6 (IL-6) (P < 0.005), IL-8 (P < 0.005), pleocytosis (P < 0.05), the albumin ratio (P < 0.0005), and the presence of oligoclonal IgG bands (P < 0.005). Cerebrospinal fluid levels of both NFL and GFAP also showed a significant correlation with MRI abnormalities ( P < 0.001). Successful cyclo- phosphamide treatment of CNS lupus resulted in sig- nificantly decreased levels of both proteins; levels of GFAP reached those observed in healthy subjects. Conclusion. This study is the first to show bio- chemical signs of neuronal and astrocytic damage in patients with neuropsychiatric lupus. It is suggested that biochemical markers of brain damage should be used as a followup tool in this patient group. Central nervous system (CNS) involvement has been reported to occur in 14–75% of patients with systemic lupus erythematosus (SLE) (1–3). The large differences in frequency relate to the diagnostic criteria applied. CNS lupus can occur at any time during the course of SLE, and the symptoms are extremely diverse (4). The features of this condition may include seizures, stroke, depression, psychosis, and disordered mentation. Minor symptoms such as headache, poor concentration, and mood swings may be attributable to other intercur- rent conditions, and differentiating the origin of such symptoms may be difficult. In addition, other diseases capable of causing CNS symptoms, such as infections, severe hypertension, metabolic derangements (associat- ed, for instance, with renal failure), or drug toxicity may coexist in patients with SLE (5). Without treatment, CNS lupus is one of the major causes of morbidity and mortality in SLE. In recent years, CNS lupus has been treated with cytotoxic drugs, which improve the disease outcome (6). The availability of beneficial treatment remedies increases the need for early recognition of CNS manifestations in lupus, as well as an evaluation of local (i.e., intrathecal) responses to lupus medication. Supported by the Go ¨teborg Medical Society, Swedish Asso- ciation Against Rheumatism, King Gustaf V Foundation, Swedish Medical Research Council, Nanna Svartz’ Foundation, Bo ¨rje Dahlin’s Foundation, Swedish National Inflammation Network, Swedish Na- tional Infection and Vaccination Network, AME Wolff Foundation, and the University of Go ¨teborg. Estelle Trysberg, MD, Karin Nylen, MD, Lars E. Rosengren, MD, PhD, Andrej Tarkowski, MD, PhD: University of Go ¨teborg, Go ¨teborg, Sweden. Address correspondence and reprint requests to Estelle Trys- berg, MD, Department of Rheumatology and Inflammation Research, University of Go ¨teborg, Guldhedsgatan 10, S-413 46 Go ¨teborg, Swe- den. E-mail: estelle@immuno.gu.se. Submitted for publication November 14, 2002; accepted in revised form June 6, 2003. 2881