Glutamic Acid Decarboxylase (GAD-65) Autoimmunity Associated With Profound Daytime Hypersomnia, Nighttime Insomnia, Mild Autonomic Neuropathy and Axonal Sensori-Motor Polyneuropathy: A Case Report on a New Phenotype

We describe the case of a 74-year-old fit and healthy man who developed a profound sleep disorder characterized by mid-day hypersomnia and debilitating insomnia. A wide range of therapies, including a large number of stimulants and hypnotics with multiple different mechanisms of action, failed to improve his condition. Trials with oral prosthetic devices and a wide range of face masks with positive pressure assistance and multiple continuous positive airway pressure (CPAP) titration studies failed to help. Along with his sleep disorder, our patient developed a slowly evolving axonal sensorimotor polyneuropathy with a subtle autonomic neuropathy. Due to the latter two conditions, a comprehensive paraneoplastic panel was obtained and revealed extremely high titer glutamic acid decarboxylase (GAD-65) autoantibodies. This was confirmed by three independent laboratories and by cerebrospinal fluid staining of rat hippocampus, revealing the classic tram-track lines along the dentate gyrus. Our patient was treated empirically with intravenous immunoglobulin. We believe that our case reveals a unique syndrome related to GAD-65 autoantibodies and adds to the growing list of GAD-65 associated diseases. This case is particularly provocative as it raises the idea to check for GAD-65 autoimmunity in patients who suffer from a profound sleep disorder resistant to conventional treatment.