Connectivity Inefficiency Caused by Structural Changes in Multiple Sclerosis

Demyelination, neuroaxonal, and astroglial damage in the white matter are contributors to the lass of structural connectivity in multiple sclerosis.

Microstructural modifications reduce physical connectivity through demyelination, neuroaxonal, and astroglial damage in patients with multiple sclerosis, leading to decreased cognition, according to a study published in NeuroImage: Clinical.

Researchers analyzed the relationship between neural connectivity through graph theory metrics as well as microstructural damage through magnetic resonance markers, and how these changes impact functional cognition. Patients with relapsing remitting or secondary progressive multiple sclerosis (n=102) and healthy volunteers (n=25) were evaluated for global disability, attention, memory, and processing speed. Magnetic resonance imagery (MRI) evaluated the frontopatietal network through radial diffusivity, for demyelination, and ratios of myo-inositol, nacetylaspartate and glutamate + glutamine with creatine, for astrogliosis, neuroaxonal integrity, and glutamatergic neurotoxicity.

The patients whose cognitive scores indicated impaired function (25%) had secondary progressive multiple sclerosis and lower global disability scores. Sixty-nine percent of patients with multiple sclerosis had abnormal global efficiency, 50% had abnormal local efficiency, and 61% had abnormal assortativity of the network. There was a statistically significant decrease in global efficiency (P=.002) and local efficiency (P<.001) and an increase of assortativity (P<.01) in patients with multiple sclerosis when compared with the healthy volunteers. The multiple logistic regression analysis indicated that the odds ratio of abnormal global efficiency was 0.95 (95% CI, 0.91-0.99, P=.011) times higher when the ration of N-acetylaspartate + N-acetylaspartylglutamate/creatine + phosphocreatine was increased by 0.01, and abnormal local efficiency was 1.39 (95% CI, 1.14-1.71, P=.001) times higher when radial diffusivity was increased by 0.01. Abnormal global efficiency had a mean cognitive score of −0.95 and abnormal local efficiency had a mean cognitive score of −0.70, both of which were lower than the mean scores the normal global or local efficiency (P=.01 and P=.048, respectively).

Future studies need to analyze the dynamics of the structural connectivity network and how the microstructural changes effect functional impairment.

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Researchers conclude that lower structural network efficiency, whether global or local, negatively impacts functional cognition. This outcome might be due to regional disorganization caused by demyelination or network collapse due to neuroaxonal damage.

This study was supported by Proyecto de Investigacion en Salud. Please refer to reference for a complete list of authors’ disclosures.


Solana E, Martinez-Heras E, Martinez-Lapiscina EH, et al. Magnetic resonance markers of tissue damage related to connectivity disruption in multiple sclerosis. Neuroimage Clin. 2018; 20: 161-168.