Improved brain MRI indices in the acute brain stem infarct sites treated with hydroxyl radical scavengers, Edaravone and hydrogen, as compared to Edaravone alone. A non-controlled study - PubMed (original) (raw)

Improved brain MRI indices in the acute brain stem infarct sites treated with hydroxyl radical scavengers, Edaravone and hydrogen, as compared to Edaravone alone. A non-controlled study

Hirohisa Ono et al. Med Gas Res. 2011.

Abstract

Background: In acute stage of cerebral infarction, MRI indices (rDWI & rADC) deteriorate during the first 3-7 days after the ictus and then gradually normalize in approximately 10 days (pseudonormalization time), although the tissue is already infarcted. Since effective treatments improve these indices significantly and in less than the natural pseudonormalization time, a combined analysis of these changes provides an opportunity for objective evaluation on the effectiveness of various treatments for cerebral infarction. Hydroxyl radicals are highly destructive to the tissue and aggravate cerebral infarction. We treated brainstem infarction patients in acute stage with hydroxyl radical scavengers (Edaravone and hydrogen) by intravenous administration and evaluated the effects of the treatment by a serial observation and analysis of these MRI indices. The effects of the treatment were evaluated and compared in two groups, an Edaravone alone group and a combined group with Edaravone and hydrogen, in order to assess beneficial effects of addition of hydrogen.

Methods: The patients were divided in Edaravone only group (E group. 26 patients) and combined treatment group with Edaravone and hydrogen enriched saline (EH group. 8 patients). The extent of the initial hump of rDWI, the initial dip of rADC and pseudo-normalization time were determined in each patient serially and averages of these data were compared in these two groups and also with the natural course in the literatures.

Results: The initial hump of rDWI reached 2.0 in the E group which was better than 2.5 of the natural course but was not as good as 1.5 of the EH group. The initial dip of rADC was 0.6 in the E group which was close to the natural course but worse than 0.8 of the EH group. Pseudonormalization time of rDWI and rADC was 9 days only in EH group but longer in other groups. Addition of hydrogen caused no side effects.

Conclusions: Administration of hydroxyl radical scavengers in acute stage of brainstem infarction improved MRI indices against the natural course. The effects were more obvious and significant in the EH group. These findings may imply the need for more frequent daily administration of hydroxyl scavenger, or possible additional hydrogen effects on scavenger mechanisms.

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Figures

Figure 1

Figure 1

Serial MRI changes in the upper brain stem lesion slices (1st & 3rd row) and lower brain stem lesion slices (2nd and 4th row) of DWI (1st & 2nd row) and ADC (3rd & 4th row) images. upper. Serial MRI of a representative patient in E group on Day 1, 3, 6 (left to right). The lesion involved two adjacent slices at the upper (1st row) and lower (2nd row) brain stem. The DWI signal intensity (whiteness) of the upper slice increased on Day3 (presence of the initial hump), but remained almost unchanged on Day 1,3& 6 in the lower slice (2nd row) by the naked eye. The reduced ADC signal intensity (blackness) of the same lesion was seen even on Day6, particularly in the lower lesion slice (4th row). lower. Serial MRI of a representative patient in EH group on Day1, 2, 7, 9 (left to right). The lesions also involved two adjacent slices. The DWI signal intensity of the upper slice (1st row) was seen on Day1 but was invisible on the Day2 &7 (absence of the initial hump). The initial hump was seen only in the anterior part of the lower lesion slice (2nd row) but not in the posterior-lateral extension of the lesion towards the cerebellum which had disappeared on Day2 & 7(absence of the initial hump). The ADC signal was clearly darker in the lower brainstem lesion (4th row) on Day 2 but disappearing on Day7 and became grey colour on Day9 (shortened pseudonormalization time and late hike, 4th row, right end).

Figure 2

Figure 2

Serial changes in rDWI (upper) and rADC (lower). upper: Daily averages of rDWI in the E group patients showed a mild initial hump (Day4 to Day8, up to 2.2) but remained less than a natural course (rDWI of 2.5, Huang et al [3]). In the EH group, the initial hump was not seen (p < 0.05 on the Day 5, 8 and 9). No shortening of the pseudonormalization time was seen in E group (the rDWI average remained above 1.2 by Day9). In the EH group, the rDWI averages on Day 8 reached the normal level of 1.2 (shortened pseudonormalization time). Lower: Daily averages of rADCs in the E group patients showed a mild initial dip (Day4 to 7). In the EH group, the initial dip was rather short lived on Day 5 but no data available on Day6 & 7. No pseudonormalization of the rADC was noted within 9 days in the E group. In the EH group, however, the shortening was seen on Day 9. Then, the rADC of EH group increased (late hike). The differences of the rADC in the two groups reached a statistical significance on the Day5, 8 and 9.

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