Sympathetic Nervous System Dysfunction in Multiple Sclerosis, Linking Neurodegeneration to a Reduced Response to Therapy

A lower than normal function of the sympathetic nervous system (SNS) has been identified early in the course of multiple sclerosis (MS) and has been shown to play a role in the pathology of the disease. In addition, the chronic use of many drugs commonly used by MS patients could further downregulate SNS by interfering with norepinephrine (NE) synthesis/release and/or interfering with the function of the adrenergic receptors in both the brain and in the periphery. This drug-induced downregulation of SNS activity, when imposed on a background of SNS dysfunction, could not only promote immune inflammatory and neurodegenerative processes, but also can lead to a reduced clinical response to immunomodulaory therapies. Furthermore, low SNS activity could contribute to a higher prevalence of disorders such as depression, fatigue and osteoporosis, which has been observed in MS patients. An algorithm could be constructed based on the combination of baseline NE plasma levels and SNS response levels to a β-adrenergic agonist stimulus. This algorithm, corrected for age and gender, would have the potential to identify MS patients who have a reduced response to immunomodulatory therapies.