Glucocorticosteroids: Risk-Benefit Appraisals in Multiple Sclerosis and MS-Associated Optic Neuritis

Glucocorticosteroids/GC are the cornerstone of immunosuppression utilized for decades in the treatment of multiple sclerosis (MS) and MS-related optic neuritis (MS-ON). Steroids are often prescribed as either 'monotherapy' or add-on in structured 'polytherapy' regimens or concomitant with other immunosuppressants and/or immunomodulatory drugs, depending upon the disease situation. This review focuses on the pharmacologic corticosteroids, such as methylprednisolone, that are prevalently utilized in MS care. Among other aims, the treatment effects on dynamic patterns of cerebral atrophy, optic nerve inflammation and neurodegeneration are evaluated, and a risk stratification of patients with MS and MS-ON is presented. It provides details on selected case reports, as well as pivotal clinical studies and attributable significant (clinically important) outcomes. It then addresses primarily the outcomes related to demyelination or neurodegeneration, myelin repair or neuroregeneration, and the undesirable such safety issues as ataxia, avascular necrosis, infections, and cerebral atrophy. At the end, we put together a critical assessment of both explicit and implicit observations on various treatment configurations, including NOAEL (no observed adverse effect level) dosing for reasons where it is currently unclear whether or ever a safe and effective clinical dosing of steroids is established in clinical trials for MS and MS-ON, discuss impartially the current state-of-knowledge, identify scientific data gaps, and offer a fresh perspective on how to improve the benefits and minimize the risks of steroids in multiple sclerosis.