Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes

Abstract

While brain atrophy occurs early in the clinical course of multiple sclerosis, exactly how early, which tissues are affected and the rate at which early atrophy occurs are unclear. Regional brain atrophy was investigated in 58 patients recruited within 3 months of onset of a clinically isolated syndrome (CIS) suggestive of multiple sclerosis, who were followed-up for 3 years. At 3 years, 31 subjects had developed multiple sclerosis as defined by the McDonald criteria, while 27 had not (13 had MRI-visible brain lesions and 14 did not). In those who developed multiple sclerosis, the mean decrease in grey matter fractional volume (GMF, as a fraction of total intracranial volume) was -0.017 (-3.3%) and was significantly larger than in the combined lesion-positive and lesion-negative CIS subjects [-0.005 (-1.1%), P = 0.001]. No decrease in white matter fractional volumes (WMF) was seen. Change in GMF correlated only modestly with the change in T2 lesion volume from baseline to year 3 (r = -0.428, P = 0.004). These results suggest that progressive grey matter, but not white matter, atrophy is seen in the earliest clinically observable stages of relapse onset multiple sclerosis, and this is only moderately related to lesion accumulation. Longer-term follow-up is required to determine whether early grey matter atrophy is associated with subsequent disability or cognitive impairment.

Subcortical and Cortical Gray Matter Atrophy in a Large Sample of Patients with Clinically Isolated Syndrome and Early Relapsing-Remitting Multiple Sclerosis

“…22 No significant differences were found in whole-brain, global GM, WM, and/or cortical volumes between the 2 groups. This confirms the results of some recent studies that showed that selective regional, but not global, atrophy occurs from clinical onset to conversion to clinically definite MS. [17][18][19][20] This study provides strong evidence that regional GM atrophy is exclusively confined to the SDGM and not to cortical regions in the first 4 years of disease duration. Our findings suggest, therefore, that future studies should concentrate more on understanding the pathogenetic mechanisms leading to selective SDGM rather than to cortical GM damage in patients with early RRMS.…”

“…[5][6][7] More recently, research has focused on determining the extent of GM pathology at the first clinical event in patients presenting with CIS [8][9][10][11][12][13][14][15][16] or on its evolution with conversion to clinically definite MS. [17][18][19][20] It has been reported that global GM volume measures are not sensitive enough to detect GM atrophy at the time of the initial attack.…”

“…[5][6][7] Other nonconventional MR imaging techniques have also contributed to determining the extent of GM damage in patients with MS. 2 The role of GM pathology in MS has come under increasingly close scrutiny, especially after it was shown that GM atrophy predicts clinical outcomes better than WM damage. [5][6][7] More recently, research has focused on determining the extent of GM pathology at the first clinical event in patients presenting with CIS [8][9][10][11][12][13][14][15][16] or on its evolution with conversion to clinically definite MS. [17][18][19][20] It has been reported that global GM volume measures are not sensitive enough to detect GM atrophy at the time of the initial attack. 11 Consequently, GM atrophy studies in patients with CIS have increasingly turned to regional segmentation techniques to identify specific structures with a stronger predilection for disease susceptibility and conversion to clinically definite MS. [8][9][10][11]13,14,16,17,19,21 The aim of this study was to investigate differences in the extent of SDGM and cortical atrophy in a large sample of patients with CIS and early RRMS.…”

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

“…However, neuroimaging studies revealed microglia activation with minimal inflammatory cell infiltrates in proximity of cortical axonal transections [19]; this gray matter abnormality occurs surprisingly early and correlates much better with permanent disability, demonstrating that microglia activation in gray matter correlates with neuron loss and MS onset ( [37,51,201,230]). …”

Upper cervical spinal cord cross‐sectional area in relapsing remitting multiple sclerosis: Application of a new technique for measuring cross‐sectional area on magnetic resonance images

“…MRI-based atrophy studies often focus on the brain, and loss of both gray matter (11,12) and white matter (13) has been shown in MS. Similarly, tissue loss in the spinal cord has been investigated in MS (7,8,10,14 -16), although less extensively than brain tissue loss, even though 90% of MS patients have spinal cord pathology (17).…”