Cell surface antibody–associated neurodegeneration

Cell surface autoantibodies have become important biomarkers of acquired autoimmune CNS disorders, and typically define potentially severe but treatable acquired autoimmune encephalitis syndromes. However, the discovery of anti-IgLON5 antibodies has forced a reappraisal of the accepted paradigms regarding cell surface antibodies and their associated clinical manifestations.1 Although anti-IgLON5 antibody is a cell surface antibody, the clinical syndrome is not an encephalitis (there is no lymphocytic inflammatory infiltration), disease onset is more chronic rather than acute, and the neurologic sequelae are not reversible with immunotherapy in most patients, with progressive neurodegeneration and high mortality. This is therefore a novel autoimmune CNS syndrome, inhabiting the borderland between autoimmunity and neurodegeneration: cell surface antibody–associated neurodegeneration. The article by Gaig et al.2 in this issue of Neurology ® extends our knowledge of the clinical features of this rare but important form of autoimmune neurodegeneration. The study describes 22 patients who were positive for anti-IgLON5 autoantibodies, as tested by the Neuroimmunology Laboratory in Barcelona, comprising the largest cohort with this condition. The main findings were that the clinical syndrome can present with sleep, brainstem, gait, cognitive, or movement disorders, but during the disease course all patients develop manifestations of disordered sleep and ventilation. The course was chronic and progressive in most patients, and 59% died during follow-up. It should be noted that it is possible that the initial description of this condition has resulted in recruitment bias, and the spectrum of symptoms and signs is different from what is described by Gaig et al.