The classic neuropathological hallmark is the presence of multifocal regions of inammatory demyelination disseminated in space and time throughout the CNS.Such lesions develop in association with breakdown of the bloodbrain barrier with trafcking of activated T lymphocytes and other immune mediators, leading to acute tissue damage principally with breakdown of myelin but also with a degree of axonal destruction.There is usually good recovery from such relapses as a result of several mechanisms: resolution of inammation, remyelination, restoration of conduction in persistently demyelinated bers, and cortical adaptation.The onset with relapses and remissions is seen in of cases.In of patients, the onset of MS is one of progressively increasing and irreversible disability. After a variable number of years this clinical pattern also emerges for of those who started with relapsing remitting disease. The progressive phase of MS has a poorer prognosis and there is compelling evidence both from neuropathological observation and the application of magnetic resonance surrogate markersthat axonal loss is the main pathological substrate for such an evolution.MULTIPLE SCLEROSIS BIOMARKERS loss is attributable to the immediate effects of acute inammation, this alone is not a sufcient explanation.Some patients, especially with primary progressive MS, have experienced few or no relapses and have little evidence on MRI scans for the past or present occurrence of inammatory lesions.On the other hand, pathological and quantitative MR imaging and normal appearing gray matter. The course is unpredictable and subject to shortterm uctuations, yet the development of irreversible disability often takes many years.The clinical scales commonly used for Fenofibric acid quantifying disability have limited sensitivity and reproducibility and do not capture all of the patients functional problems.Clinical assessments have an intrinsic subjective component and are prone to bias if either the patient or the investigator is unblinded.Denitive phase trials with a clinical endpoint either relapse rate or sustained increase in disabilityrequire the participation of large patient numbers, followed over at least or years, with a control versus active treatment parallel groups design and with double blinding.The trials are very expensive, cumbersome, and are slow in providing answers.To be a reliable surrogate measure, the outcome should be sensitive to Beta-Sitosterol disease evolution such that it provides an answer on therapeutic effect quickly and in small numbers of subjects.Most importantly, it should reect and predict an important clinical outcome.In MS this outcome is either of the following: reduction in relapse rate or slowing the accumulation of irreversible disability.In view of the pathological basis of these clinical features it follows that biological surrogates proposed for MS fall broadly into two categories: inammatory white matter lesions neurodegenerative changes in lesions, NAWM, or NAGM. The rest of this review will discuss what has been learned using surrogate measures in MS.Because MR outcomes have been far and away the most useful and widely investigated outcomes, they will be the principal focus, although brief comments on other approaches will also be made where appropriate.Very recently, the presence of serum antibodies to myelin peptides has been reported to predict conversion from a clinically isolated syndrome to clinically denite MS.