Paraneoplastic and idiopathic autoimmune neurologic disorders: approach to diagnosis and treatment

Autoimmune neurology is a rapidly emerging new subspecialty that encompasses the diagnosis and treatment of neurologic disorders with an autoimmune (paraneoplastic or noncancer-associated) basis. The last decade has seen a dramatic rise in the discovery of neural-specific autoantibodies and their target antigens. Laboratory testing, on a service basis, is now available for most of these neural-specific autoantibodies and they serve as diagnostic markers, in some instances directing the physician toward specific cancer types (e.g., N-methyl-d-aspartate receptor antibodies for teratoma; CRMP5-IgG for small-cell cancer) and assisting in therapeutic decision making. Antibodies targeting intracellular proteins (nuclear and intracytoplasmic enzymes, transcription factors, and RNA binding proteins) serve as markers of cytotoxic effector T-cell-mediated injury and are generally poorly responsive to immunotherapy. By contrast, antibodies targeting plasma membrane proteins that are extracellular and accessible (neurotransmitter receptors, ion channels, water channels, and channel-complex proteins) may act as pathogenic effectors and often imply immunotherapy responsiveness. Magnetic resonance imaging, electrophysiologic studies, functional imaging, and neuropsychologic evaluations provide objective evidence of neurologic dysfunction by which the success of immunotherapy may be measured.