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
Background: Patients with primary progressive multiple sclerosis (PPMS) often develop severe disability despite low levels of abnormality on conventional magnetic resonance imaging (MRI). This may relate to diffuse pa...Background: Patients with primary progressive multiple sclerosis (PPMS) often develop severe disability despite low levels of abnormality on conventional magnetic resonance imaging (MRI). This may relate to diffuse pathological processes occurring in normal appearing brain tissue (NABT) involving both white matter (NAWM) and grey matter (NAGM). Magnetisation transfer imaging (MTI) is capable of identifying these processes and may be particularly informative when applied to patients with early PPMS. Aim: To assess the relationship between abnormalities in NABT identified by MTI and disability and other radiological data in patients with early PPMS. Methods: We studied 43 patients within 5 years of disease onset and 43 controls. The Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) were scored. Magnetisation transfer ratios (MTR) of NABT, NAWM, and NAGM were calculated and the following MTR parameters were measured: mean, peak height, peak location, and MTR value at the 25th, 50th, and 75th percentiles. Proton density, T2, T1, and gadolinium enhancing lesion loads were also calculated. Results: Differences were found between patients and controls in mean, peak height, and peak location of NAWM and NAGM (p≤ 0.001). Weak to moderate correlations were found between MTR parameters and disability in both NAWM and NAGM. Strong correlations between MTR parameters and lesion loads were found, particularly in NAWM. Conclusion: MTR abnormalities are seen in NAWM and NAGM in early PPMS and both are associated with disability. NAWM MTR abnormalities are more closely related to conventional MRI measures than those seen in NAGM.展开更多
There are few longitudinal studies of cognition in patients with multiple sclerosis, and the results of these studies remain inconclusive. No serial neuropsychological data of an exclusively primary progressive series...There are few longitudinal studies of cognition in patients with multiple sclerosis, and the results of these studies remain inconclusive. No serial neuropsychological data of an exclusively primary progressive series are available. Cross-sectional analyses have revealed significant correlations between cognition and magnetic resonance imaging (MRI) parameters in primary progressive multiple sclerosis (PPMS). This study investigated cognitive and MRI change in 99 PPMS patients from five European centres for 2 years. They were assessed at 12 month intervals using the Brief Repeatable Battery, a reasoning test, and a measure of depression. The MRI parameters of T1 hypointensity load, T2 lesion load, and partial brain volume were also calculated at each time point. There were no significant differences between the mean cognitive scores of the patients at year 0 and year 2. However, one-third of the patients demonstrated absolute cognitive decline on individual test scores. Results indicated that initial cognitive status on entry into the study was a good predictor of cognitive ability at 2 years. There was only a small number of significant correlations between changes in cognition and changes on MRI, notably T1 hypointensity load with the two attentional tasks (r = -0.266, P = 0.017; r = -0.303, P = 0.012). It is probable that multiple factors underlie this weak relation between the cognitive and MRI measures.展开更多
Objective: To determine the time course of brain atrophy during treatment with once- weekly IM interferon β - 1a (IFNβ - 1a). Methods: The MRI cohort (n = 386) of the European IFNβ - 1a dose comparison study in rel...Objective: To determine the time course of brain atrophy during treatment with once- weekly IM interferon β - 1a (IFNβ - 1a). Methods: The MRI cohort (n = 386) of the European IFNβ - 1a dose comparison study in relapsing multiple sclerosis (MS)- was analyzed. In addition to baseline and three annual scans, a frequent subgroup (n = 138) had two scans before treatment initiation and scans at months 4, 5, 6, 10, and 11. Brain parenchymal fraction (BPF), a normalized measure of whole- brain atrophy, and volume of Gd- enhancing lesions (T1Gd) and T2 hyperintense lesions (T2LL) were evaluated. Results: BPF decrease was - 0.686% (first year), - 0.377% (second year), and - 0.378% (third year). Analysis of the frequent subgroup showed that 68% of the first- year BPF decrease occurred during the first 4 months of treatment. This change was paralleled by a drop in T1Gd and T2LL. In the frequent subgroup, an annualized atrophy rate was determined by a regression slope for the pretreatment period and from month 4 of treatment onward. Annualized pretreatment rate (- 1.06% ) was significantly higher than the under- treatment rate (- 0.33% ). Conclusions: In the first year of treatment with anti- inflammatory agents, atrophy measurements are possibly confounded by resolution of inflammatory edema or more remote effects of previous damage to the CNS. The atrophy rate reduction observed after treatment month 4 may reflect a beneficial but partial effect of interferon β - 1a and was sustained over the 3- year study period.展开更多
Objectives: Previous studies have shown that upper cervical cord atrophy (UCCA) occurs in multiple sclerosis (MS), particularly in those disabled and with primary or secondary progressive disease. It is less clear how...Objectives: Previous studies have shown that upper cervical cord atrophy (UCCA) occurs in multiple sclerosis (MS), particularly in those disabled and with primary or secondary progressive disease. It is less clear how early it can be detected in relapsing-remitting (RR) MS, and whether early cord atrophy relates to the concurrent or future clinical course. Methods: Twenty seven RR MS patients (median disease duration 1.7 years, in all cases < 3 years from onset) were recruited along with 20 controls. They were followed for up to 3 years with a yearly assessment of UCCA and clinical function measured by the Expanded Disability Status Scale (EDSS) and MS Functional Composite Score (MSFC). Clinical and MRI correlations were investigated. Statistical models adjusted for covariates including total intracranial volume. Results: Longitudinal analysis showed a significant decrease in UCCA in patients both within the patient cohort (p < 0.001) and in comparison with controls (p = 0.001). There was a significant increase in EDSS (p = 0.008) but no significant change in MSFC. The rate of UCCA loss did not correlate with clinical change or with change in brain volume. Conclusions: In summary, serial UCCA measurement detects the development of spinal cord atrophy in clinically early RR MS.展开更多
The EVIDENCE study was a direct comparative study of two dose regimens of interferon (IFN) beta- 1a used in the treatment of relapsing- remitting multiple sclerosis (RRMS): 30 mcg intramuscularly once weekly (qw; n=33...The EVIDENCE study was a direct comparative study of two dose regimens of interferon (IFN) beta- 1a used in the treatment of relapsing- remitting multiple sclerosis (RRMS): 30 mcg intramuscularly once weekly (qw; n=338) and 44 mcg subcutaneously three times weekly (tiw; n = 339). The study continued for an average of 64 weeks. The safety population consisted of all patients receiving at least one dose of study drug. Clinical assessments occurred every 4 weeks for 24 weeks and then every 12 weeks. Blood tests for safety were taken at baseline and at weeks 4 and 12, and every 12 weeks thereafter. Overall adverse events were more common with the 44 mcg tiw regimen (p = 0.007), and were due predominantly to differences in injection- site reactions. The majority of adverse events were rated mild by investigators. Hepatic and haematological adverse events and asymptomatic laboratory abnormalities were more common with 44 mcg tiw (p < 0.001), with no difference seen for severe events. Flu- like symptoms were more common with 30 mcg qw (p = 0.031), were more severe and persisted for longer. Serious adverse events were comparable for both groups, as were drug discontinuations. In conclusion, although adverse events were more common with high- dose, high- frequency IFN therapy, differences were primarily for mild events and did not affect treatment adherence. Based on superior clinical and magnetic resonance imaging outcomes over an average of 64 weeks, coupled with modest safety differences, the riskbenefit ratio for IFN therapy in RRMS favours the 44 mcg tiw regimen over this period of time.展开更多
Objective: Multiple sclerosis (MS) is a chronic progressive disease with multiple neurological impairments. The disease can also dramatically affect the health-related quality of life of patients. The objective of thi...Objective: Multiple sclerosis (MS) is a chronic progressive disease with multiple neurological impairments. The disease can also dramatically affect the health-related quality of life of patients. The objective of this study was to investigate the validation of the translated and cross-culturally adapted MSQOL- 54 in 183 Turkish MS patients. Methods: 183 adults classified as having definite MS patients were enrolled into the study. Patients were classified into four severity groups according to the expanded disability status scale (EDSS); group I(EDSS 0- 4), group II (EDSS 4.5- 5.5), group III (EDSS 6- 6.5) and group IV (EDSS 7- 8). MSQOL- 54 questionnaire were translated and culturally adapted into Turkish. Associations between age, gender, disease duration,EDSS score, marital status, education and health insurance and the MSQOL- 54 physical and mental health composite scores were determined. Results: The mean age of the 183 patients (138 female and 45 male) was 39 ± 10 years. The questionnaire was well accepted but small cultural adaptations were required. EDSS scores showed significant associations with the MSQOL- 54 physical and mental health composite scores. From the different EDSS groups only, the group I (EDSS 0- 4) score was significantly associated with the physical health composite as well as the disease duration showed significant correlation with the physical and mental composite scores. None of the other EDSS groups and the other parameters showed correlation with physical health composite or mental health composite. Conclusion: Assessment of quality of life of MS patients in addition to disease severity and disability level is important, because it provides unique information that is important to patients and to clinicians. A translation of an existing MS-targeted HRQOL measure from US English into Turkish was easily administered and well accepted in a Turkish MS sample.展开更多
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.
文摘Background: Patients with primary progressive multiple sclerosis (PPMS) often develop severe disability despite low levels of abnormality on conventional magnetic resonance imaging (MRI). This may relate to diffuse pathological processes occurring in normal appearing brain tissue (NABT) involving both white matter (NAWM) and grey matter (NAGM). Magnetisation transfer imaging (MTI) is capable of identifying these processes and may be particularly informative when applied to patients with early PPMS. Aim: To assess the relationship between abnormalities in NABT identified by MTI and disability and other radiological data in patients with early PPMS. Methods: We studied 43 patients within 5 years of disease onset and 43 controls. The Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) were scored. Magnetisation transfer ratios (MTR) of NABT, NAWM, and NAGM were calculated and the following MTR parameters were measured: mean, peak height, peak location, and MTR value at the 25th, 50th, and 75th percentiles. Proton density, T2, T1, and gadolinium enhancing lesion loads were also calculated. Results: Differences were found between patients and controls in mean, peak height, and peak location of NAWM and NAGM (p≤ 0.001). Weak to moderate correlations were found between MTR parameters and disability in both NAWM and NAGM. Strong correlations between MTR parameters and lesion loads were found, particularly in NAWM. Conclusion: MTR abnormalities are seen in NAWM and NAGM in early PPMS and both are associated with disability. NAWM MTR abnormalities are more closely related to conventional MRI measures than those seen in NAGM.
文摘There are few longitudinal studies of cognition in patients with multiple sclerosis, and the results of these studies remain inconclusive. No serial neuropsychological data of an exclusively primary progressive series are available. Cross-sectional analyses have revealed significant correlations between cognition and magnetic resonance imaging (MRI) parameters in primary progressive multiple sclerosis (PPMS). This study investigated cognitive and MRI change in 99 PPMS patients from five European centres for 2 years. They were assessed at 12 month intervals using the Brief Repeatable Battery, a reasoning test, and a measure of depression. The MRI parameters of T1 hypointensity load, T2 lesion load, and partial brain volume were also calculated at each time point. There were no significant differences between the mean cognitive scores of the patients at year 0 and year 2. However, one-third of the patients demonstrated absolute cognitive decline on individual test scores. Results indicated that initial cognitive status on entry into the study was a good predictor of cognitive ability at 2 years. There was only a small number of significant correlations between changes in cognition and changes on MRI, notably T1 hypointensity load with the two attentional tasks (r = -0.266, P = 0.017; r = -0.303, P = 0.012). It is probable that multiple factors underlie this weak relation between the cognitive and MRI measures.
文摘Objective: To determine the time course of brain atrophy during treatment with once- weekly IM interferon β - 1a (IFNβ - 1a). Methods: The MRI cohort (n = 386) of the European IFNβ - 1a dose comparison study in relapsing multiple sclerosis (MS)- was analyzed. In addition to baseline and three annual scans, a frequent subgroup (n = 138) had two scans before treatment initiation and scans at months 4, 5, 6, 10, and 11. Brain parenchymal fraction (BPF), a normalized measure of whole- brain atrophy, and volume of Gd- enhancing lesions (T1Gd) and T2 hyperintense lesions (T2LL) were evaluated. Results: BPF decrease was - 0.686% (first year), - 0.377% (second year), and - 0.378% (third year). Analysis of the frequent subgroup showed that 68% of the first- year BPF decrease occurred during the first 4 months of treatment. This change was paralleled by a drop in T1Gd and T2LL. In the frequent subgroup, an annualized atrophy rate was determined by a regression slope for the pretreatment period and from month 4 of treatment onward. Annualized pretreatment rate (- 1.06% ) was significantly higher than the under- treatment rate (- 0.33% ). Conclusions: In the first year of treatment with anti- inflammatory agents, atrophy measurements are possibly confounded by resolution of inflammatory edema or more remote effects of previous damage to the CNS. The atrophy rate reduction observed after treatment month 4 may reflect a beneficial but partial effect of interferon β - 1a and was sustained over the 3- year study period.
文摘Objectives: Previous studies have shown that upper cervical cord atrophy (UCCA) occurs in multiple sclerosis (MS), particularly in those disabled and with primary or secondary progressive disease. It is less clear how early it can be detected in relapsing-remitting (RR) MS, and whether early cord atrophy relates to the concurrent or future clinical course. Methods: Twenty seven RR MS patients (median disease duration 1.7 years, in all cases < 3 years from onset) were recruited along with 20 controls. They were followed for up to 3 years with a yearly assessment of UCCA and clinical function measured by the Expanded Disability Status Scale (EDSS) and MS Functional Composite Score (MSFC). Clinical and MRI correlations were investigated. Statistical models adjusted for covariates including total intracranial volume. Results: Longitudinal analysis showed a significant decrease in UCCA in patients both within the patient cohort (p < 0.001) and in comparison with controls (p = 0.001). There was a significant increase in EDSS (p = 0.008) but no significant change in MSFC. The rate of UCCA loss did not correlate with clinical change or with change in brain volume. Conclusions: In summary, serial UCCA measurement detects the development of spinal cord atrophy in clinically early RR MS.
文摘The EVIDENCE study was a direct comparative study of two dose regimens of interferon (IFN) beta- 1a used in the treatment of relapsing- remitting multiple sclerosis (RRMS): 30 mcg intramuscularly once weekly (qw; n=338) and 44 mcg subcutaneously three times weekly (tiw; n = 339). The study continued for an average of 64 weeks. The safety population consisted of all patients receiving at least one dose of study drug. Clinical assessments occurred every 4 weeks for 24 weeks and then every 12 weeks. Blood tests for safety were taken at baseline and at weeks 4 and 12, and every 12 weeks thereafter. Overall adverse events were more common with the 44 mcg tiw regimen (p = 0.007), and were due predominantly to differences in injection- site reactions. The majority of adverse events were rated mild by investigators. Hepatic and haematological adverse events and asymptomatic laboratory abnormalities were more common with 44 mcg tiw (p < 0.001), with no difference seen for severe events. Flu- like symptoms were more common with 30 mcg qw (p = 0.031), were more severe and persisted for longer. Serious adverse events were comparable for both groups, as were drug discontinuations. In conclusion, although adverse events were more common with high- dose, high- frequency IFN therapy, differences were primarily for mild events and did not affect treatment adherence. Based on superior clinical and magnetic resonance imaging outcomes over an average of 64 weeks, coupled with modest safety differences, the riskbenefit ratio for IFN therapy in RRMS favours the 44 mcg tiw regimen over this period of time.
文摘Objective: Multiple sclerosis (MS) is a chronic progressive disease with multiple neurological impairments. The disease can also dramatically affect the health-related quality of life of patients. The objective of this study was to investigate the validation of the translated and cross-culturally adapted MSQOL- 54 in 183 Turkish MS patients. Methods: 183 adults classified as having definite MS patients were enrolled into the study. Patients were classified into four severity groups according to the expanded disability status scale (EDSS); group I(EDSS 0- 4), group II (EDSS 4.5- 5.5), group III (EDSS 6- 6.5) and group IV (EDSS 7- 8). MSQOL- 54 questionnaire were translated and culturally adapted into Turkish. Associations between age, gender, disease duration,EDSS score, marital status, education and health insurance and the MSQOL- 54 physical and mental health composite scores were determined. Results: The mean age of the 183 patients (138 female and 45 male) was 39 ± 10 years. The questionnaire was well accepted but small cultural adaptations were required. EDSS scores showed significant associations with the MSQOL- 54 physical and mental health composite scores. From the different EDSS groups only, the group I (EDSS 0- 4) score was significantly associated with the physical health composite as well as the disease duration showed significant correlation with the physical and mental composite scores. None of the other EDSS groups and the other parameters showed correlation with physical health composite or mental health composite. Conclusion: Assessment of quality of life of MS patients in addition to disease severity and disability level is important, because it provides unique information that is important to patients and to clinicians. A translation of an existing MS-targeted HRQOL measure from US English into Turkish was easily administered and well accepted in a Turkish MS sample.
