Sanna Giovanni, Bertolaccini Maria Laura, Khamashta Munther A
Department of Rheumatology, Homerton University Hospital, London E9 6SR, UK.
Curr Pharm Des. 2008;14(13):1261-9. doi: 10.2174/138161208799316401.
The involvement of the central nervous system (CNS) is one of the major causes of morbidity and mortality in systemic lupus erythematosus (SLE) patients and the less understood aspect of the disease. Its recognition and treatment continue to represent a major diagnostic and therapeutic challenge. Due to the lack of controlled randomized trials, current therapeutic approach is still empirical and based on clinical experience. The therapeutic choice depends on accurate diagnosis, identification of underlying pathogenic mechanism, severity of the presenting neuropsychiatric symptoms, and on prompt identification and management of contributing causes of CNS disease. Mild neuropsychiatric manifestations may need symptomatic treatment only. In more severe CNS disease it is important to distinguish between thrombotic and non-thrombotic mechanisms. Focal CNS manifestations, particularly TIA and stroke, are associated with the presence of antiphospholipid antibodies (aPL). Anticoagulation is warranted in patients with thrombotic disease, particularly in those with the antiphospholipid (Hughes) syndrome (APS). Other CNS manifestations, such as demyelinating syndrome, transverse myelitis, chorea, seizures, migraine and/or cognitive dysfunction, when associated with persistent positivity for aPL, may also benefit from anticoagulation in selected patients. Severe diffuse CNS manifestations, such as acute confusional state, generalised seizures, mood disorders and psychosis, generally require corticosteroids in the first instance. Pulse intravenous cyclophosphamide therapy may help when more severe manifestations are refractory to corticosteroids and other immunosuppressive agents, generally when response is not seen in 3-5 days. Plasmapheresis may also be added in severe cases of symptoms refractory to conventional treatment. Intravenous immunoglobulins, mycophenolate mofetil, rituximab, intratecal methotrexate and dexametasone deserve further studies to confirm their usefulness in the treatment of neuropsychiatric SLE. This article reviews the clinical approach to therapy in patients with SLE and neuropsychiatric involvement.
中枢神经系统（CNS）受累是系统性红斑狼疮（SLE）患者发病和死亡的主要原因之一，也是该疾病中了解较少的方面。对其的识别和治疗仍然是主要的诊断和治疗挑战。由于缺乏对照随机试验，目前的治疗方法仍然是经验性的，基于临床经验。治疗选择取决于准确的诊断、潜在致病机制的识别、所呈现的神经精神症状的严重程度，以及对中枢神经系统疾病促成原因的及时识别和处理。轻度神经精神表现可能仅需对症治疗。在更严重的中枢神经系统疾病中，区分血栓形成和非血栓形成机制很重要。局灶性中枢神经系统表现，特别是短暂性脑缺血发作（TIA）和中风，与抗磷脂抗体（aPL）的存在有关。血栓形成性疾病患者，特别是抗磷脂（休斯）综合征（APS）患者，有必要进行抗凝治疗。其他中枢神经系统表现，如脱髓鞘综合征、横贯性脊髓炎、舞蹈症、癫痫发作、偏头痛和/或认知功能障碍，当与aPL持续阳性相关时，部分患者也可能从抗凝治疗中获益。严重的弥漫性中枢神经系统表现，如急性意识模糊状态、全身性癫痫发作、情绪障碍和精神病，一般首先需要使用皮质类固醇。当更严重的表现对皮质类固醇和其他免疫抑制剂难治时，一般在3 - 5天内未见反应时，脉冲静脉注射环磷酰胺治疗可能会有帮助。对于常规治疗难治的严重症状病例，也可加用血浆置换。静脉注射免疫球蛋白、霉酚酸酯、利妥昔单抗、鞘内注射甲氨蝶呤和地塞米松值得进一步研究以证实它们在治疗神经精神性SLE中的有效性。本文综述了SLE合并神经精神受累患者的临床治疗方法。
