Fernando Figueira, MD, and his associates from the Hospital São Francisco, in Rio De Janeiro, Brazil, called for expanded requirements for "disease-free" designation in multiple sclerosis (MS) patients in a Multiple Sclerosis Treatment poster session at the American Academy of Neurology (AAN) 2013 Annual Meeting.

Figueira believes that the current paradigm of “disease-free” MS, which is based on the lack of clinical or conventional MRI features characteristic of the inflammatory aspects of MS, may be missing other degenerative changes. These degenerative changes are known to begin early in the course of the disease and are not usually reversible.

He argued that axonal loss — a major determinant of disability — can be a valuable marker for optimizing disease-modifying treatment (DMT) for MS. Previous studies have shown that axonal loss progression may occur without overt clinical and imaging expression, requiring more sophisticated MRI techniques of detection.

Figueira and his team have developed a simple, practical and reproducible orthogonal measure, called the Corpus Callosum Index (CCI), using a midsaggital MRI T1W slice. It shows a linear correlation with brain parenchymal fraction (BPF) and has been utilized in routine practice to monitor axonal loss.

Figueira and his colleagues prospectively studied a cohort of 191 consecutive, non-selected patients with relapsing-remitting MS (RRMS) and diagnosed according to 2001 McDonald criteria who were on regular immunomodulatory therapy. The subjects were submitted to systematic serial clinical examinations, laboratory testing and conventional MRI evaluation with a focus on relapses, progression of Expanded Disability Status Scale (EDSS) scores and the presence of T1W Gd-enhancing or T2W new or enlarging lesions. On conventional MRI sequences, the group studied whole brain and callosal atrophy, using BPF and CCI as markers.

The results obtained from the 191 RRMS subjects were compared on an annual basis with data from a control group of 23 patients with other neurological, non-inflammatory diseases, as well as data from a historical series of 54 non-selected, consecutive patients with secondary progressive MS (SPMS) in the institution’s MS program. Of the 191 study patients, 89 (46.5 percent) experienced neither relapses nor sustained progression of EDSS scores, and they also showed no evidence of active MRI lesions after 5-years, thus meeting the conventional criteria for disease-free status. Nevertheless, 43 (48.3 percent) of those patients showed a progressive reduction in BPF and CCI, comparable with those stratified as suboptimal responders, and some of them reached scores comparable to patients with progressive MS.

Figueira said the data demonstrates that axonal loss can be detected early in the MS disease process and followed by means of a practical method employing conventional MRI sequences. He and his team propose that the CCI or another validated axonal loss measurement should be included as a requirement to support the designation of "disease-free" status in patients. It follows that axonal loss should also be a primary therapeutic target.