The number of different antibody-associated disorders of the central nervous system and the clinical phenotypes encountered are increasing steadily. Because these patients have potentially reversible diseases, it is incumbent on the neurologist to treat them promptly and effectively. However, although some diseases respond fairly well and quickly to conventional immunotherapies, some can be very challenging.
Neuromyelitis optica (NMO) is a severe and disabling condition caused by antibodies to the water channel aquaporin 4 (AQP4), which is expressed on the astrocyte end feet abutting the pia and vascular endothelium. Antibodies to AQP4 lead to complement-dependent inflammation and antigen internalization, and treatment aims to reduce antibody levels. However, as AQP4 antibodies seldom disappear, the patient remains susceptible to further inflammatory lesions of the optic nerve or spinal cord, with each relapse resulting in increased disability and a risk of permanent blindness or paralysis. Thus, relapse prevention must be a major goal of therapy. In addition, neuropathic pain, mostly related to spinal cord involvement, is a prominent and often treatment-resistant feature in NMO1 that has now become well recognized.
Irani SR, Vincent A. Targeting the Interleukin 6 Receptor to Treat Neuromyelitis Optica. JAMA Neurol. 2015;72(7):747-748. doi:10.1001/jamaneurol.2015.0579