LAUSR

In multiple sclerosis (MS), the majority of patients experience neurologic relapses followed by recovery and later—on average 10 to 15 years after onset in adult patients1,2 and 20 years after onset in pediatric patients3—develop progressive neurologic decline. A small number, ≈10% to 15%, experience neurologic progression from the onset. While infiltrative inflammation has been implicated in the relapsing phase of the disease, the gradually progressive aspect of MS is poorly understood. Much work has associated disease progression with overall measures of tissue injury,4 with the biological correlate being global load of axonal injury and neuronal death. In contrast, others have shown that spinal cord lesions are the primary driver of progressive MS.5 These observations have led to a debate: what is causing progressive MS? Is it overall tissue injury or strategically ill-placed lesions? This question has direct clinical ramifications in that clinicians need to decide whether they should consider all lesions with equal importance or place greater importance on some lesions than on others, thus prompting more aggressive treatment strategies in these patients.