Gray Matter, White Matter Ratio Predicts Multiple Sclerosis Progression

White Matter Hyperintensities vs MS continued
White Matter Hyperintensities vs MS continued
Previous MRI studies focused on gray matter changes only.

The ratio of gray matter (GM) to normal appearing white matter (NAWM) predicts progression  of relapsing remitting MS (RRMS) and conversion to secondary progressive, according to a study reported recently in the European Journal of Neurology.

Marcello Moccia, MD, and his colleagues at the University of Naples Federico II and Imperial College in London evaluated changes in brain volume in 149 newly-diagnosed patients with RRMS through segmentation and brain volumetry on magnetic resonance imaging (MRI). The researchers found that patients with a higher ratio of GM to NAWM at diagnosis were 90% less likely to progress or reach EDSS of 4.0, compared to those with a lower ratio.

Dr Moccia said that while previous MRI studies focused on gray matter changes only, the current study specifically explored the potential dynamic between gray and white matter changes, as both areas are known to be involved in early stages of MS. Damage to white matter has been previously reported to occur through mechanisms that are independent of gray matter changes,2,3 and it remains unclear whether the influence of the GM:NAWM ratio is determined by one or both.

Decline in gray matter has been associated in previous studies with progression according to the Expanded Disability Status Scale (EDSS).4,5 The current study drew upon data collected from the MS Clinical Care and Research Center at the University of Naples over a period of 10.6 years (+ 2.4 years) to form a retrospective cohort. Over a mean period of 6.7 + 3.1 years, 58 patients (39%) reached an EDSS of 4.0.  Mean time to conversion to SPMS in 34 patients (23%) was 7.5 + 1.8 years.

All of the patients were given disease-modifying therapy (DMT) at the time of diagnosis, and the majority (62%) either switched therapy or discontinued altogether during the study period. Those who switched may have done so up to four times. Closer investigation revealed that patients who converted to SPMS were more likely to have switched therapies more than once during the previous years.

Annualized relapse rate (ARR) was 0.27 + 2.0 (mean time to relapse = 2.1 + 2.4 years); all 149 patients in the study experienced at least one relapse, with no significant correlation to age, gender, duration of disease, EDSS at baseline, or number of DMTs used. Relapse rates also did not vary according to location of changes (gray vs white matter).

The results of this study suggest that changes to both gray and white matter are related to disease evolution and may be variably affected in ways that are predictive of disease progression.


  1. Moccia M, Quarantelli M, Lanzillo R, et al. Grey:white matter ratio at diagnosis and the risk of 10-year multiple sclerosis progression. Eur J Neurol. 2016; doi:10.1111/ene.13183. 
  2. Calabrese M, Magliozzi R, Ciccarelli O,et al. Exploring the origins of grey matter damage in multiple sclerosis. Nat Rev Neurosci. 2015;16:147-158.
  3. Sethi V, Yousry T, Muhlert N, et al. A longitudinal study of cortical grey matter lesion subtypes in relapse-onset multiple sclerosis. J Neurol Neurosurg Psychiatry. 2016;87:750-753.
  4. Lavorgna L, Bonavita S, Ippolito D,et al. Clinical and magnetic resonance imaging predictors of disease progression in multiple sclerosis: a nine-year follow-up study. Mult Scler. 2014;20:220-226.
  5. Chen JT, Narayanan S, Collins DL, et al. Relating neocortical pathology to disability progression in multiple sclerosis using MRI. NeuroImage. 2004;23:1168-1175.