MR biomarkers may help ID patients at risk for MS conversion

Development of thalamic and central atrophy as measured by MR may accurately predict which patients with clinically isolated syndrome (CIS) will convert to clinically definite multiple sclerosis (CDMS) over a two-year period, according to a study published April 23 in Radiology. The findings could change how physicians view MS and how drugs are developed, the researchers noted. 

An initial CIS episode precedes MS for approximately 85 percent of patients. MS diagnosis hinges on clinical history, neurological studies, and onset of a second attack as well as detection of new and enlarging lesions with T2-weighted MRI. Recent research has focused on the thalamus as a potential MR biomarker to predict conversion from CIS to MS.

Robert Zivadinov, MD, PhD, from the Buffalo Neuroimaging Analysis Center at the University of Buffalo in New York, and colleagues sought to determine the link between development of thalamic and cortical atrophy and conversion to MS.

The researchers enrolled 216 CIS patients ages 18 to 55 years in a prospective study between 2005 and 2009. Patients underwent MR imaging at baseline, six months, one year and two years.

Three radiologists reviewed the number and volume of contrast-enhanced T2 lesions and analyzed changes in whole-brain and tissue-specific global and regional gray matter volumes.

A total of 42.6 percent of patients experienced relapse during the two-year study. Regression analysis showed increase in lateral ventricle volume and decrease in thalamic volume were the most significant variables in MS compared with stable CIS patients.   

“This finding suggests that monitoring development of thalamic and central atrophy may be relevant for identifying patients at high risk for conversion to CDMS in future clinical trials involving CIS patients, in addition to counting T2 and CE [contrast-enhanced] lesions or assessing their volumes,” wrote Zivadinov et al.

The researchers offered that measurement of thalamic atrophy may be an ideal outcome in clinical trials and cited several reasons. Specifically:

  • Thalamic atrophy occurred more rapidly than whole-brain, gray matter, white matter or cortical atrophy;
  • Thalamic atrophy was linked with MS development in all analyses and did not correlate with absence of clinical disease;
  • Development of thalamic atrophy was detected in CIS patients from initial onset; and
  • The thalamus is potentially less affected by pseudoatrophy than global or tissue-specific brain volume measure.

“Thalamic atrophy may become a hallmark of how we look at the disease and how we develop new drugs to treat it,” Zivadinov said in a release.

The research team continues to follow the study group, and will publish four-year results in summer 2014. “The next step is to look at where the lesions develop over two years with respect to the location of the atrophy,” Zivadinov said. “Thalamic atrophy cannot be explained entirely by accumulation of lesions; there must be an independent component that leads to loss of thalamus.”