Unanticipated demyelinating pathology of the CNS

Incidentally identified anomalies within the CNS that are highly suggestive of demyelinating disease have been extensively described in neuropathological series, and are increasingly being detected during premortem investigations. With the exception of studies that focused specifically on the prevalence of this entity, the observed anomalies are unanticipated and unrelated to the intended purpose of the examination. The discovery of MRI technology, and its subsequent widespread adoption in the clinic, has facilitated the identification of such cases. The natural course of individuals with incidentally identified demyelinating anomalies is unknown at present. This Review focuses on the history and nosology of unexpected demyelinating pathology, encompassing both autopsy data and MRI-based antemortem investigations of large cohorts, as well as family members at high risk of developing multiple sclerosis. Longitudinal clinical data acquired from prospectively followed cohorts will also be reviewed. In addition, I discuss the estimated prevalence of demyelinating pathology, the currently proposed criteria for its identification, implications for therapeutic intervention, and predictors of disease progression.