Clinical relevance of cortical network dynamics in early primary progressive MS.

BACKGROUND: Structural cortical networks (SCNs) reflect the covariance between the cortical thickness of different brain regions, which may share common functions and a common developmental evolution. SCNs appear abnormal in neurodegenerative conditions such as Alzheimer's and Parkinson's diseases, but have never been assessed in primary progressive multiple sclerosis (PPMS). OBJECTIVE: The aim of this study was to test whether SCNs are abnormal in early PPMS and change over 5 years, and correlate with disability worsening. METHODS: A total of 29 PPMS patients and 13 healthy controls underwent clinical and brain magnetic resonance imaging (MRI) assessments for 5 years. Baseline and 5-year follow-up cortical thickness values were obtained and used to build correlation matrices, considered as weighted graphs to obtain network metrics. Bootstrap-based statistics assessed SCN differences between patients and controls and between patients with fast and slow progression. RESULTS: At baseline, patients showed features of lower connectivity (p = 0.02) and efficiency (p < 0.001) than controls. Over 5 years, patients, especially those with fastest clinical progression, showed significant changes suggesting an increase in network connectivity (p < 0.001) and efficiency (p < 0.02), not observed in controls. CONCLUSION: SCNs are abnormal in early PPMS. Longitudinal SCN changes demonstrated a switch from low- to high-efficiency networks especially among fast progressors, indicating their clinical relevance.

Guidelines for the conduct of clinical trials in spinal cord injury: Neuroimaging biomarkers.

Traumatic spinal cord injury (SCI) leads to immediate neuronal and axonal damage at the focal injury site and triggers secondary pathologic series of events resulting in sensorimotor and autonomic dysfunction below the level of injury. Although there is no cure for SCI, neuroprotective and regenerative therapies show promising results at the preclinical stage. There is a pressing need to develop non-invasive outcome measures that can indicate whether a candidate therapeutic agent or a cocktail of therapeutic agents are positively altering the underlying disease processes. Recent conventional MRI studies have quantified spinal cord lesion characteristics and elucidated their relationship between severity of injury to clinical impairment and recovery. Next to the quantification of the primary cord damage, quantitative MRI measures of spinal cord (rostrocaudally to the lesion site) and brain integrity have demonstrated progressive and specific neurodegeneration of afferent and efferent neuronal pathways. MRI could therefore play a key role to ultimately uncover the relationship between clinical impairment/recovery and injury-induced neurodegenerative changes in the spinal cord and brain. Moreover, neuroimaging biomarkers hold promises to improve clinical trial design and efficiency through better patient stratification. The purpose of this narrative review is therefore to propose a guideline of clinically available MRI sequences and their derived neuroimaging biomarkers that have the potential to assess tissue damage at the macro- and microstructural level after SCI. In this piece, we make a recommendation for the use of key MRI sequences-both conventional and advanced-for clinical work-up and clinical trials.