The role of endothelial dysfunction in the pathogenesis of neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric manifestations of systemic lupus erythematosus are common and disabling yet their pathogenesis is poorly understood. We investigated the role of cerebrovascular endothelial dysfunction in systemic lupus erythematosus and its neuropsychiatric manifestations. Subjects with systemic lupus erythematosus were recruited prospectively along with matched healthy control subjects. The presence of neuropsychiatric systemic lupus erythematosus syndromes was ascertained according to standard definitions. Cerebrovascular reactivity, an indicator of endothelial function, was measured using transcranial Doppler ultrasound. Sixty-one subjects (58 female, 3 male) with systemic lupus erythematosus and 70 control subjects were assessed. Sixty patients (98%) reported at least one neuropsychiatric manifestation, the most prevalent being headache and cognitive dysfunction. There was no significant difference in cerebrovascular reactivity between cases and controls (3.06 vs 3.06, p=0.99). Subjects with systemic lupus erythematosus and a history of stroke and/or transient ischaemic attack had significantly higher cerebrovascular reactivity than those without (3.99 vs 2.79, p = 0.007). No association was found between the presence of other neuropsychiatric syndromes or systemic lupus erythematosus-related variables and altered cerebrovascular reactivity. In conclusion, cerebrovascular endothelial dysfunction is not present in the majority of subjects with systemic lupus erythematosus. However, the role of endothelial dysfunction in the pathogenesis of stroke and transient ischaemic attack in systemic lupus erythematosus merits further investigation. Lupus (2010) 19, 797-802.