Nervous involvement in systemic lupus erythematosus (SLE) is common and can manifest as a range of neurological and psychiatric features, but it is uncommon for the nervous system to be the primary manifestation. This paper reports a case of an 18-year-old male who was diagnosed with obsessive- compulsive disorder in a psychiatric hospital after presenting with forced hand washing and repeated checking of doors. He was admitted to our hospital with incontinence and weakness of both lower limbs. After admission, MRI examination of the head revealed abnormal signals in the left temporal lobe and insula, along with cerebral infarction with hemorrhage; therefore, necrosis and surrounding edema were suspected. Laboratory tests detected anti-nuclear antibody (1:1000) and anti-nRNP/Sm antibody (++) and decreased serum levels of C3 and C4. The imaging and laboratory results above led to the diagnosis of neuropsychiatric lupus (NPSLE). After methylprednisolone (MP) pulse therapy plus cyclophosphamide (CTX) and belimumab treatment, the abnormal signal foci and surrounding edema in the left temporal lobe of MR were improved, urination was controlled, and the muscle strength of both lower limbs was restored. During the 8-month follow-up, the patient’s muscle strength gradually returned to normal, and the condition is stable as of this writing. In conclusion, adolescents who present with neuropsychiatric symptoms as the first manifestation of SLE should receive early autoimmunological examinations to avoid misdiagnosis or missed treatment opportunities. (Am J Transl Med 2021. 5:166-172).