Abstract
Background: Multiple Sclerosis (MS) lesions in white matter (WM) are easily detected with conventional MRI which induce inflammation thereby generating contrast. WM lesions do not consistently explain the extent of clinical disability, cognitive impairment, or the source of an exacerbation. Gray matter (GM) structures including the cerebral cortex and various deep nuclei are known to be affected early in Primary Progressive Multiple Sclerosis (PPMS) and drive disease progression, disability, fatigue, and cognitive dysfunction. However, little is known about how rapidly GM lesions develop and accumulate over time.Objective: The purpose of this study is to analyze the degree and rate of progression in 25 patients with PPMS using voxel-based automated volumetric quantitation.Methods: This is a retrospective single-center study which includes a cohort of 25 patients with PPMS scanned utilizing NeuroQuant® 3 dimensional voxel-based morphometry (3D VBM) automated analysis and database and restudied after a period of ~1 year (11–14 months). Comparisons with normative data were acquired for whole brain, forebrain parenchyma, cortical GM, hippocampus, thalamus, superior and inferior lateral ventricles. GM volume changes were correlated with their clinical motor and cognitive scores using Extended Disability Status Scales (EDSS) and Montreal Cognitive Assessments (MoCA).Results: Steep reductions occurred in cerebral cortical GM and deep GM nuclei volumes which correlated with each patient's clinical and cognitive impairment. The median observed percentile volume losses were statistically significant compared with the 50th percentile for each GM component. Longitudinal assessments of an unselected sample of one dozen patients involved in the PPMS study showed prominent losses occurring mainly in cortical GM and hippocampus which were reflected in their EDSS and MoCA. The longitudinal results were compared with a similar sample of patients having Relapsing MS (RMS) whose GM values were largely in normal range, annualized volume GM changes were much less, while WM hyperintensities were in abnormal range in half the unselected cases.Conclusions: Knowledge of the degree and rapidity with which cortical atrophy and deep GM volume loss develops clarifies the source of progressive cognitive and clinical decline in PPMS.
Highlights
white matter (WM) abnormalities obtained on routine Brain and Spinal Cord MRI often fail to explain the source of an Multiple Sclerosis (MS) exacerbation, or the degree of cognitive and physical impairment that MS patients experience, a circumstance described as the “clinico-radiological paradox” [1, 2] Histopathologic analysis has demonstrated a substantial burden of pathology in the cerebral cortex [3,4,5] and deep Gray matter (GM) structures [6] and is independent of WM demyelination [2, 6,7,8,9]
WM abnormalities obtained on routine Brain and Spinal Cord MRI often fail to explain the source of an MS exacerbation, or the degree of cognitive and physical impairment that MS patients experience, a circumstance described as the “clinico-radiological paradox” [1, 2] Histopathologic analysis has demonstrated a substantial burden of pathology in the cerebral cortex [3,4,5] and deep GM structures [6] and is independent of WM demyelination [2, 6,7,8,9]
The results provide a striking contrast as RMS patients have GM values mostly in normal range when compared to Primary Progressive Multiple Sclerosis (PPMS) and relatively small annualized volume changes
Summary
WM abnormalities obtained on routine Brain and Spinal Cord MRI often fail to explain the source of an MS exacerbation, or the degree of cognitive and physical impairment that MS patients experience, a circumstance described as the “clinico-radiological paradox” [1, 2] Histopathologic analysis has demonstrated a substantial burden of pathology in the cerebral cortex [3,4,5] and deep GM structures [6] and is independent of WM demyelination [2, 6,7,8,9]. GM lesions have been difficult to detect using conventional MRI techniques such as T2-weighted spin-echo or FLAIR images, due to the low contrast they produce as they have little T-cell related inflammation [3, 4, 14,15,16,17] or disruption of the blood brain barrier [18]. Focal cortical lesions fail to be visualized using these conventional MR images because they tend to be small, and are difficult to distinguish from surrounding normal appearing GM [19]. They tend to have partial volume effects with WM and CSF [20]. Little is known about how rapidly GM lesions develop and accumulate over time
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
