In order to establish if neuropsychiatric systemic lupus erythematosus (NPSLE) can be identified by any characteristic other than those used to diagnose the neuropsychiatric (NP) disease itself, we retrospectively reviewed 98 systemic lupus erythematosus (SLE) patients followed over a mean period of 10 years. NPSLE was identified in 22 patients. Stroke and generalized seizures were the most frequent NP manifestations. The NPSLE and non-NPSLE groups were similar with regard to demographic characteristics, ACR criteria, serum autoantibodies, and frequency of hypertension and hypercholesterolemia. Of note, compared to the non-NPSLE group, NPSLE was associated with a higher frequency of smoking (78 versus 26%), organ damage (73 versus 34%), and cumulative mortality rate (14 versus 7%). The series of patients was further analysed according to the presence of antiphospholipid syndrome (APS). Significantly, the interval between the onset of NP disease and SLE diagnosis was shorter in the APS？ ( years) than in the APS+ ( years) groups. Recurrence and/or persistence of NP events were only documented in the APS？ group. Overall cumulative mortality was highest in NPSLE and in APS+ patients with inadequate anticoagulation control, identifying an aspect that requires improved vigilance and the development of novel therapeutic modalities. 1. Introduction In the course of their disease, many patients with systemic lupus erythematosus (SLE) develop neurologic and psychiatric symptoms. According to recent reviews neuropsychiatric (NP) disease occurs in as many as 30–56% of all SLE patients [1, 2]. However, the diagnosis of neuropsychiatric SLE (NPSLE) remains difficult. In a prospective study, only approximately one-fourth of NP events were attributed to SLE [3]. In addition, the proportion of NP cases amongst SLE patients may be overestimated because events such as cognitive impairment, mood, anxiety disorders, and headaches depend on assessing the subjective complaints of patients and are very frequent in the general population. The American College of Rheumatology (ACR) has listed 19 clinical entities that define NPSLE [4], but these do not differentiate, in population-based studies, NPSLE patients from non-SLE controls. The exclusion of headache, mild mood disorders, anxiety, mild cognitive dysfunction, and polyneuropathy without electrophysiological confirmation decreases the frequency of NPSLE diagnosis by half and increases the specificity of the ACR criteria from 46% to 93% [5]. NP events attributed to SLE occur mainly in the 6 months prior to, and in the first
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