Changes in Corpus Callosum Area Indicate Progression to MS

Daniel M. Keller, PhD

July 19, 2012

July 19, 2012 (Prague, Czech Republic) — Changes in the area of the corpus callosum on magnetic resonance imaging (MRI) and T2 lesion volume are the most sensitive markers of the available MRI indicators for the risk for progression from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS), Dana Horakova, MD, PhDD, told delegates during a presentation here at the 22nd Meeting of the European Neurological Society (ENS).

She said quantitative MRI can help in monitoring treatment and is feasible in clinical practice.

These data were derived from an ongoing observational study that Dr. Horakova and colleagues are performing to evaluate early treatment with interferon beta-1a in high-risk patients with CIS, defined as a first neurologic episode lasting at least 24 hours, caused by inflammation/demyelination in the central nervous system. About one half of patients with CIS go on to fulfill criteria for CDMS within 6 years of CIS onset.

The first patient was enrolled in 2005, and by mid-2009, the researchers had enrolled 220 patients. Analysis of 2-year data from 217 patients, based on quarterly clinical assessments and semiannual MRI scans, was completed in July 2011.

At study entry, patient ages ranged from 15 to 55 years, with an average age of 30 years in the group with stable CIS (n = 125) and 28 years in the group that progressed to CDMS (n = 92; P = .01). Sixty-seven percent were female, the time since the first event was 0.9 to 1.1 months, and Expanded Disability Status Scale scores in both groups were 1.5 with an interquartile range of 1.5 to 2.

At baseline, T2 lesion volume was 2.9 ± 4.0 cm3 in the stable CIS group and 4.4 ± 5.5 cm3 in the CDMS group (P = .02). Baseline areas of the corpus callosum did not differ significantly between the groups (4.4 ± 0.6 cm2 vs 4.3 ± 0.6 cm2, respectively). There were also no significant differences between the 2 groups in T1 lesion volume, brain volume, brain parenchymal fraction, or gray matter or white matter volumes.

At 24 months, when adjusted for age, sex, and changes in treatment, the T2 and T1 lesion volumes were greater in the CDMS group than in the group of patients with stable CIS by 1.6 cm3 (P = .001) and 0.3 cm3 (P = .003), respectively. Brain volume remained the same between the 2 groups during the 2 years of follow-up, but the CDMS group lost brain parenchymal fraction faster, with a loss of 0.6% compared with the stable CIS group (P = .03).

One of the factors most indicative of progression was the area of the corpus callosum. "Especially when we measure the corpus callosum and the evolution of the atrophy of the corpus callosum, you can see that there is really a clear difference," Dr. Horakova reported. "It is obvious already after 6 and 12 months that differentiated these 2 subgroups." The CDMS patients lost 0.23 cm3 (3%) more area by 24 months (a loss of area of about 4% for the CDMS patients vs about 1% for the CIS patients, P < .001).

A change of corpus callosum volume of 1% or more at 6 months combined with a baseline T2 lesion volume of 5 cm3 or greater predicted conversion to CDMS by 24 months, compared with a situation in which neither factor occurred (hazard ratio, 6.5; 95% confidence interval [CI], 3.4 - 12). Baseline T2 lesion volume of greater than 5 cm3 alone was also a significant predictor of progression (P = .003).

Session moderator Xavier Montalban, MD, PhD, chairman of the Department of Neurology and director of the Multiple Sclerosis Center of Catalonia at Vall d'Hebron University Hospital and professor of neurology at the Autonomous University of Barcelona in Spain, who was not involved in the study, commented to Medscape Medical News that the study provides insight on a new quantitative marker of progression to CDMS.

"We don't have to look only to the T2 lesions or gadolinium-enhanced lesions but also to the neurodegenerative phenomena," he said. "One of these is the corpus callosum atrophy that they found to be an important predictor of treatment response during the first 6 months."

But he questioned whether this added information would better inform a patient's treatment. "Is that enough to change our anti-inflammatory drug? Do we have any other better neuroprotective [therapy] nowadays?" he asked, then answered, "I'm not sure about that." He said it is too early to know whether measuring corpus callosum volume would be useful in judging whether a patient is responding to a particular drug.

When asked if this technique is feasible for the community neurologist to apply, he said, "No, no, no, no. This is for very specific MS centers where they have very good techniques and they are reproducible. It's nothing for the general neurologist at all."

Dr. Horakova said the quantitative MRI scans must be done on the same machine over time, which Dr. Montalban called "very strange, since she had the same machine since 1999, while we have changed [our] machine 4 times [since then], so that's amazing. That's very good information, in fact."

This investigator-initiated study was supported by Biogen Idec and the Czech Ministry of Education. Disclosure information has been requested but not yet received from Dr. Horakova. Dr. Montalban has disclosed no relevant financial relationships.

22nd Meeting of the European Neurological Society. Abstract O-293. Presented June 11, 2012.

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