Loss of gyrification is associated with disability progression in multiple sclerosis
Jonadab Dos Santos Silva1, Francesco La Rosa1, William A Mullins2, Prasanna Parvathaneni2, Josefina Maranzano3, Daniel Reich4, Erin Beck1
1Department of Neurology, Icahn School of Medicine at Mount Sinai, 2National Institute of Neurological Disorders and Stroke, National Institutes of Health, 3McGill University, Montreal Neurological Institute, 4National Institute of Neurological Disorders and Stroke, National Institutes of Health, Neuroimmunology Branch, NINDS
Objective:
Examine longitudinal changes in cortical gyrification in multiple sclerosis (MS) and the link between cortical reshaping, lesion load, and disability.
Background:
Local gyrification index (LGI) is a measure of the degree and pattern of cortical folding and is associated with worsening disability in neurodegenerative diseases, but is not always correlated with brain or cortical atrophy. In MS, changes in LGI may indicate regions undergoing remodeling.
Design/Methods:
47 people with MS (29 relapsing-remitting, 15 secondary progressive, 3 primary progressive; age 49±11 years; 65% female; median disease duration 12 years [IQR, 17.5]) underwent longitudinal 3T and 7T brain MRI and disability assessments (median follow-up 2.3 years, range 1.7–4.0). Cortical and white matter lesions were manually segmented on 7T (0.5mm3 MP2RAGE (median of 4 acquisitions), 0.5mm3 T2*w GRE) and 3T (FLAIR, MP2RAGE, T2w) images respectively. LGI was measured at each timepoint on 3T MP2RAGE T1w images (Freesurfer 7.1).
Results:
Across the cohort, LGI decreased over time in the cingulate, superior frontal, and medial orbitofrontal gyri (PFWE<0.05, adjusted for age and sex). Within individual cortical regions, correlation between change in LGI and change in cortical thickness and volume was weak to moderate. The number of cortical areas with ≥5% LGI reduction was associated with worsening timed 25-foot walk (ρ=0.302, P=0.039) and 9-hole peg test (ρ=0.361, P=0.013). Global gyrification decrease was associated with higher cortical (ρ=-0.296, P=0.043) and white matter lesion burden (ρ=-0.303, P=0.039). An age-adjusted backward regression model used to determine the influence of baseline cortical and white matter lesion load on LGI changes predicted 16.2% of LGI variance (P=0.001), and higher cortical lesion burden predicted gyrification loss (β=-0.403, P=0.005).
Conclusions:
Loss of gyrification is associated with worsening disability and lesion burden, especially in the cortex. Further investigation of LGI in MS may elucidate the factors influencing cortical remodeling and how cortical remodeling contributes to disability.