Neuropsychiatric manifestation in systemic lupus erythematosus (NPSLE) is one of the most recalcitrant complications of the disease. According to the 1999 ACR nomenclature and case definitions, diffuse psychiatric/neuropsychological syndromes in NPSLE (anxiety disorder, acute confusional state, cognitive dysfunction, mood disorder, psychosis) (diffuse NPSLE) present psychiatric manifestations unlike neurologic syndromes (focal NPSLE) originating from focal CNS lesions, such as cerebrovascular disease, demyelinating syndrome, headache, aseptic meningitis, chorea, seizures and myelopathy. A number of studies have reported that diffuse NPSLE is usually associated with the presence of autoantibodies against neuronal cells in serum as well as in cerebrospinal fluid (CSF). Moreover, IL-6 has been shown to be elevated in CSF of patients with diffuse NPSLE.

Recently, it has been demonstrated that the severity of blood-brain barrier damages plays a crucial role in the development of acute confusional state, the severest form of diffuse NPSLE through the accelerated entry of larger amounts of autoantibodies to NMDA receptor subunit NR2 into the CNS. Since the importance of autoantibodies in the NPSLE has been now evident, such an aggressive treatment, especially B cell depleting therapy, would make sense in that it would reduce the levels of pathogenic autoantibodies, leading to a better prognosis of NPSLE.

<b>Epidemiology;                                                                         Naoyuki Tsuchiya</b> <p><b>Genetics;                                                                 &nbs</b></p>p;   Hiroshi Furukawa<p></p> <p><b>Immunology and pathogenesis;                                  Shunsei Hirohata</b></p> <p><b>Pathology;                                                                  Shunsei Hirohata, Masahisa Kyogoku</b></p> <p></p>Clinical Features;                                                       Yoshiyuki Arinuma<p></p> <p><b>Cytokines                                                                    Taku Yoshio</b></p><p></p> <p><b>Diagnosis and Differential diagnosis                           Taku Yoshio</b></p> <p><b>Imaging of NBD;                                                        Tom W. Huizinga</b></p> <p><b>Psychiatic symptoms;                &nb</b></p>sp;                                             Katsuji Nishimura <p></p> <p><b>Treatment;                                                                  John G. Hanly</b></p> <p><b>Promising treatment alternatives;      </b></p>                       Dimitrious T. Boumpas<p></p> <p><b>Prognosis;                                                                   Shinsuke Yasuda</b></p>