['Central nonfocal neuropsychiatric systemic lupus erythematosus (NPSLE) manifests as cognitive dysfunction, acute confusional state, seizures, and psychosis. Valvular heart disease (VHD) is currently not a causal consideration of nonfocal NPSLE.', 'The objective of this study was to determine whether VHD is associated with nonfocal NPSLE.', 'Twenty-eight patients with SLE underwent: 1) clinical and laboratory evaluations; 2) neuropsychiatric evaluation; 3) brain magnetic resonance imaging (MRI); and 4) transesophageal echocardiography (TEE). Their findings were compared with those of 28 age- and-sex matched healthy volunteers.', 'Eighteen patients (64%) had nonfocal NPSLE. Cerebral infarcts on MRI were more common in patients with than without NPSLE (50% vs 10%, P=0.048) and antiphospholipid antibodies (aPL) were associated with old cerebral infarcts (P=0.03). Valvular heart disease was detected in 20 patients (71%) of whom 20 (71%) had valve thickening, 17 (61%) had valve regurgitation, and 15 (53%) had valve vegetations (12 on the mitral valve). Mitral valve vegetations were more common in patients with than without nonfocal NPSLE and in those with old cerebral infarcts (61% vs 10% and 75% vs 30%, respectively, P<or=0.02 for both). The nonneurologic activity of SLE and mitral valve vegetations were the only independent predictors of NPSLE (odds ratio [OR], 1.27 per unit value; confidence interval [CI], 1.1-1.6; P=0.03; and OR, 16.5; CI, 1.26-217; P=0.03, respectively). Among controls, none had neuropsychiatric syndromes, 4 (15%) had MRI abnormalities, and 3 (11%) had VHD (all P<or=0.001 vs patients).'] Is valvular heart disease associated with nonfocal neuropsychiatric systemic lupus erythematosus?