Background: Brain atrophy, in excess of that seen with normal aging, has been observed early in the clinical course of relapsing-remitting multiple sclerosis (RRMS). Previous work has suggested that at this stage of t...Background: Brain atrophy, in excess of that seen with normal aging, has been observed early in the clinical course of relapsing-remitting multiple sclerosis (RRMS). Previous work has suggested that at this stage of the disease, gray mat ter (GM) atrophy progresses more rapidly than the white matter (WM) atrophy. Obj ectives: To characterize the evolution of GM and WM volumes over 2 years, and th eir associations with lesion loads in a cohort of patients with clinically early RRMS. Methods: Twenty-one patients with RRMS (mean age 37.5 years, mean diseas e duration from symptom onset 2.1 years) and 10 healthy control subjects (mean a ge 37.1 years)-were studied. Tissue volumes, as fractions of total intracranial volumes, were estimated at baseline and 1-and 2-year follow-up. Brain parenc hymal fractions (BPF), GM fractions (GMF), and WM fractions (WMF) were estimated . In subjects with MS, brain lesion loads were determined on conventional T2-we ighted along with pre-and post-gadolinium (Gd) enhanced T1-weighted images at each timepoint. Results: A decrease in GMF was observed in subjects with MS vs normal controls over the 2 years of the study (mean -2.1%vs -1.0%, p=0.044), while no change was seen in WMF over the same period (mean -0.09%vs +0.09%, p=0.812). However, when the MS cohort was divided in half, dependent upon chang e in Gd-enhancing lesion load over 2 years (n=20), a decrease in WMF was seen i n the group (n=10) with the largest decline in Gd volume, whereas WMF increased in the other half (n=10) concurrent with a net increase in volume of Gd-enhanci ng lesions (difference between groups: p=0.034). Conclusions: Increasing gray ma tter but not white matter (WM) atrophy was observed early in the clinical course of relapsing-remitting multiple sclerosis. Fluctuations in inflammatory WM les ions appear to be related to volume changes in WM over this time period.展开更多
Previous in vivo proton magnetic resonance spectroscopic imaging ( 1H-MRSI) studies have found reduced levels of N-acetyl-aspartate (NAA) in multiple sclerosis (MS) lesions, the surrounding normal-appearing white matt...Previous in vivo proton magnetic resonance spectroscopic imaging ( 1H-MRSI) studies have found reduced levels of N-acetyl-aspartate (NAA) in multiple sclerosis (MS) lesions, the surrounding normal-appearing white matter (NAWM) and cortical grey matter (CGM), suggesting neuronal and axonal dysfunction and loss. Other metabolites, such as myoinositol (Ins), creatine (Cr), choline (Cho), and glutamate plus glutamine (Glx), can also be quantified by 1H-MRSI, and studies have indicated that concentrations of these metabolites may also be altered in MS. Relatively little is known about the time course of such metabolite changes. This preliminary study aimed to characterise changes in total NAA (tNAA, the sum of NAA and N-acetyl-aspartyl-glutamate), Cr, Cho, Ins and Glx concentrations in NAWM and in CGM, and their relationship with clinical outcome, in subjects with clinically early relapsing-remitting MS (RRMS). Twenty RRMS subjects and 10 healthy control subjects underwent 1H-MRSI examinations yearly for two years. Using the LCModel, tNAA, Cr, Cho, Ins and Glx concentrations were estimated both in NAWM and CGM. At baseline, the concentration of tNAA was significantly reduced in the NAWM of the MS patients compared to the control group (-7 %, p = 0.003), as well as in the CGM (-8.7 %, p = 0.009). NAWM tNAA concentrations tended to recover from baseline, but otherwise tissue metabolite profiles did not significantly change in the MS subjects, or relatively between MS and healthy control subjects. While neuronal and axonal damage is apparent from the early clinical stages of MS, this study suggests that initially it may be partly reversible. Compared with other MR imaging measures, serial 1H-MRSI maybe relatively less sen sitive to progressive pathological tissue changes in early RRMS.展开更多
文摘Background: Brain atrophy, in excess of that seen with normal aging, has been observed early in the clinical course of relapsing-remitting multiple sclerosis (RRMS). Previous work has suggested that at this stage of the disease, gray mat ter (GM) atrophy progresses more rapidly than the white matter (WM) atrophy. Obj ectives: To characterize the evolution of GM and WM volumes over 2 years, and th eir associations with lesion loads in a cohort of patients with clinically early RRMS. Methods: Twenty-one patients with RRMS (mean age 37.5 years, mean diseas e duration from symptom onset 2.1 years) and 10 healthy control subjects (mean a ge 37.1 years)-were studied. Tissue volumes, as fractions of total intracranial volumes, were estimated at baseline and 1-and 2-year follow-up. Brain parenc hymal fractions (BPF), GM fractions (GMF), and WM fractions (WMF) were estimated . In subjects with MS, brain lesion loads were determined on conventional T2-we ighted along with pre-and post-gadolinium (Gd) enhanced T1-weighted images at each timepoint. Results: A decrease in GMF was observed in subjects with MS vs normal controls over the 2 years of the study (mean -2.1%vs -1.0%, p=0.044), while no change was seen in WMF over the same period (mean -0.09%vs +0.09%, p=0.812). However, when the MS cohort was divided in half, dependent upon chang e in Gd-enhancing lesion load over 2 years (n=20), a decrease in WMF was seen i n the group (n=10) with the largest decline in Gd volume, whereas WMF increased in the other half (n=10) concurrent with a net increase in volume of Gd-enhanci ng lesions (difference between groups: p=0.034). Conclusions: Increasing gray ma tter but not white matter (WM) atrophy was observed early in the clinical course of relapsing-remitting multiple sclerosis. Fluctuations in inflammatory WM les ions appear to be related to volume changes in WM over this time period.
文摘Previous in vivo proton magnetic resonance spectroscopic imaging ( 1H-MRSI) studies have found reduced levels of N-acetyl-aspartate (NAA) in multiple sclerosis (MS) lesions, the surrounding normal-appearing white matter (NAWM) and cortical grey matter (CGM), suggesting neuronal and axonal dysfunction and loss. Other metabolites, such as myoinositol (Ins), creatine (Cr), choline (Cho), and glutamate plus glutamine (Glx), can also be quantified by 1H-MRSI, and studies have indicated that concentrations of these metabolites may also be altered in MS. Relatively little is known about the time course of such metabolite changes. This preliminary study aimed to characterise changes in total NAA (tNAA, the sum of NAA and N-acetyl-aspartyl-glutamate), Cr, Cho, Ins and Glx concentrations in NAWM and in CGM, and their relationship with clinical outcome, in subjects with clinically early relapsing-remitting MS (RRMS). Twenty RRMS subjects and 10 healthy control subjects underwent 1H-MRSI examinations yearly for two years. Using the LCModel, tNAA, Cr, Cho, Ins and Glx concentrations were estimated both in NAWM and CGM. At baseline, the concentration of tNAA was significantly reduced in the NAWM of the MS patients compared to the control group (-7 %, p = 0.003), as well as in the CGM (-8.7 %, p = 0.009). NAWM tNAA concentrations tended to recover from baseline, but otherwise tissue metabolite profiles did not significantly change in the MS subjects, or relatively between MS and healthy control subjects. While neuronal and axonal damage is apparent from the early clinical stages of MS, this study suggests that initially it may be partly reversible. Compared with other MR imaging measures, serial 1H-MRSI maybe relatively less sen sitive to progressive pathological tissue changes in early RRMS.
