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

Abstract

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-ofknowledge, identify scientific data gaps, and offer a fresh perspective on how to improve the benefits and minimize the risks of steroids in multiple sclerosis.

Steroids Impact on Myelin Repair, Neurogenesis and Visual Pathway in Multiple Sclerosis: Preclinical Perspectives

“…Third, the consistencyof-association of GC-induced lesion repair, which is evident to a considerable degree in early periods after treatments of MS, has presumably promoted continued use of intense GCs. Little attentions seem given to plausibility of GC-resistance (at least in a subset of MS), ineffectiveness of GCs in reducing the disability progression, and GC-induced degeneration of CNS and other cells [1].…”

“…In the new MRI studies depicting SDGM abnormalities, most patients were on DMT, and exposed to excess steroids prior to or during the study entry. Whether the cohorts with a progressive disease course were either responders or non-responders to the steroids are unclear (see further; [1]). …”

“…Despite availability of many disease-modifying-therapies (DMT), neurodegeneration continues to spread to different regions of brain in multiple sclerosis (MS), manifesting as the marked decreases in whole-brain volume and gray matter (GM) in addition to increases in cerebral white matter (reviewed in [1]) and extensive spinal cord lesions [2,3].…”