Background Several double blind placebo controlled trials of relapsing remi tting multiple sclerosis have shown beneficial effects of intravenous immunoglob ulin (IVIG) on relapse rate and disability. The European Stu...Background Several double blind placebo controlled trials of relapsing remi tting multiple sclerosis have shown beneficial effects of intravenous immunoglob ulin (IVIG) on relapse rate and disability. The European Study on Intravenous I mmunoglobulin in Multiple Sclerosis set out to test IVIG in the secondary progre ssive phase of the disease. Methods 318 patients with clinically definite second ary progressive multiple sclerosis (mean age 44 years [SD 7]) were randomly as si gned IVIG 1 g/kg per month (n=159) or an equivalent volume of placebo (albumin 0 1%; n=159) for 27 months. After baseline investigation, clinical assessments were made every 3 months and MRI was repeated after 12 months and 24 months. The primary outcome was confirmed worsening of disability as defined by the time to first confirmed progression on the expanded disability status scale (EDSS). Ana lyses were by intention to treat. Findings 19 patients in the IVIG group and 39 in the placebo group terminated study treatment prematurely but were included in the analyses. IVIG treatment had no beneficial effect on time to confirmed EDSS progression (hazard ratio 1 11 [95%CI 0 80-1 53]-for IVIG versus placeb o) . The annual relapse rate was 0 46 in both groups. No significant differences b etween the treatment groups were found in any of the other clinical outcome meas ures or in the change of T2 lesion load over time. The treatment was generally well tolerated, although deep venous thrombosis, pulmonary embolism, or both occ urred in seven patients with risk factors for thromboembolism (IVIG six, placebo one). Interpretation Treatment with IVIG in this study did not show any clinica l benefit and therefore cannot be recommended for patients with secondary progre ssive multiple sclerosis.展开更多
The severity of tissue changes associated with incidental white matter hyperintensities (WMH) in the elderly cannot be sufficiently determined by conventional MRI. We, therefore, performed a regional analysis of the m...The severity of tissue changes associated with incidental white matter hyperintensities (WMH) in the elderly cannot be sufficiently determined by conventional MRI. We, therefore, performed a regional analysis of the magnetization transfer ratio (MTR) maps obtained on a 1.5 T scanner from 198 neurologically asymptomatic participants of the Austrian Stroke Prevention Study (mean age 70, age range 52-87 years) in regard to WMH and predefined areas of normal appearing brain tissue. Fluid attenuated inversion recovery MRI was used to grade lesion severity and for lesion volume measurements. The MTR of WMH was always significantly lower than that of normal appearing white matter (NAWM) with an overall relative reduction of 10%and decreased significantly with increasing scores of WMH severity (P = 0.02) and WMH volume (r = -0.24, P = 0.0016). NAWM MTR was not different between subjects with very few and extensive WMH and the WMH volume was associated with NAWM MTR of the frontal lobes only. Concerning a possible impact on cerebral functioning the MTR of the frontal NAWM was significantly associated with fine motor dexterity (P = 0.04) but not with cognitive performance. A significant decline of the MTR with aging was seen in both NAWM and cortex but not in WMH. We conclude that MTR measurements can serve to quantify WMH associated tissue damage. It is predominantly focal, relatively mild, increases with lesion size and may have remote effects on the frontal white matter.展开更多
文摘Background Several double blind placebo controlled trials of relapsing remi tting multiple sclerosis have shown beneficial effects of intravenous immunoglob ulin (IVIG) on relapse rate and disability. The European Study on Intravenous I mmunoglobulin in Multiple Sclerosis set out to test IVIG in the secondary progre ssive phase of the disease. Methods 318 patients with clinically definite second ary progressive multiple sclerosis (mean age 44 years [SD 7]) were randomly as si gned IVIG 1 g/kg per month (n=159) or an equivalent volume of placebo (albumin 0 1%; n=159) for 27 months. After baseline investigation, clinical assessments were made every 3 months and MRI was repeated after 12 months and 24 months. The primary outcome was confirmed worsening of disability as defined by the time to first confirmed progression on the expanded disability status scale (EDSS). Ana lyses were by intention to treat. Findings 19 patients in the IVIG group and 39 in the placebo group terminated study treatment prematurely but were included in the analyses. IVIG treatment had no beneficial effect on time to confirmed EDSS progression (hazard ratio 1 11 [95%CI 0 80-1 53]-for IVIG versus placeb o) . The annual relapse rate was 0 46 in both groups. No significant differences b etween the treatment groups were found in any of the other clinical outcome meas ures or in the change of T2 lesion load over time. The treatment was generally well tolerated, although deep venous thrombosis, pulmonary embolism, or both occ urred in seven patients with risk factors for thromboembolism (IVIG six, placebo one). Interpretation Treatment with IVIG in this study did not show any clinica l benefit and therefore cannot be recommended for patients with secondary progre ssive multiple sclerosis.
文摘The severity of tissue changes associated with incidental white matter hyperintensities (WMH) in the elderly cannot be sufficiently determined by conventional MRI. We, therefore, performed a regional analysis of the magnetization transfer ratio (MTR) maps obtained on a 1.5 T scanner from 198 neurologically asymptomatic participants of the Austrian Stroke Prevention Study (mean age 70, age range 52-87 years) in regard to WMH and predefined areas of normal appearing brain tissue. Fluid attenuated inversion recovery MRI was used to grade lesion severity and for lesion volume measurements. The MTR of WMH was always significantly lower than that of normal appearing white matter (NAWM) with an overall relative reduction of 10%and decreased significantly with increasing scores of WMH severity (P = 0.02) and WMH volume (r = -0.24, P = 0.0016). NAWM MTR was not different between subjects with very few and extensive WMH and the WMH volume was associated with NAWM MTR of the frontal lobes only. Concerning a possible impact on cerebral functioning the MTR of the frontal NAWM was significantly associated with fine motor dexterity (P = 0.04) but not with cognitive performance. A significant decline of the MTR with aging was seen in both NAWM and cortex but not in WMH. We conclude that MTR measurements can serve to quantify WMH associated tissue damage. It is predominantly focal, relatively mild, increases with lesion size and may have remote effects on the frontal white matter.
