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Effects of Edaravone on Muscle Atrophy and Locomotor Function in Patients with Ischemic Stroke (a Randomized Controlled Pilot Study)

Background and Objective: Stroke patients with severe leg paralysis are often bedridden in the acute and subacute phase, which increases the risk of disuse muscle atrophy in the chronic phase. The evidence to date indicates that oxidative stress plays an important role in the mechanism of disuse muscle atrophy. Therefore, the aim of this study was to determine if long-term radical scavenger treatment with edaravone following an acute stroke prevents the progression of disuse muscle atrophy and improves leg locomotor function in the chronic phase.

Methods: This randomized controlled pilot study was conducted at 19 acute stroke and rehabilitation centers across Japan. Forty-seven ischemic stroke patients with at least leg motor weakness admitted within 24 hours of onset were randomly assigned to receive continuous intravenous infusions of edaravone 30mg twice daily for 3 days (short-term group) or 10–14 days (long-term group).

The primary endpoints of the study included the degree of leg disuse muscle atrophy, as measured by the percentage change from baseline in femoral muscle circumference 15 cm above the knee, and the improvement in leg locomotor function, as assessed by the maximum walking speed over 10 m, 3 months after the onset of stroke.

Results: Three-month follow-up was completed by a total of 41 patients (21 in the short-term group and 20 in the long-term group). On admission, there was no significant difference in the severity of stroke or the grade of leg paresis between the two treatment groups. The grade of disuse muscle atrophy and incidence of gait impairment 3 weeks after stroke onset were also similar between the short- and long-term groups.

However, disuse muscle atrophy of the paretic and non-paretic legs was significantly less severe in the long-term versus the short-term treatment group (3.6 – 5.9% and 1.5 – 6.0% vs 8.3 – 5.2% and 5.7 – 6.4%; p< 0.01 and p < 0.05) 3 months after stroke onset. Additionally, the maximum walking speed over a distance of 10m was significantly greater in the long-term group (98 – 67 vs 54 – 55 cm/sec; p < 0.05).

Conclusion: Edaravone treatment for up to 14 days suppresses the progression of disuse muscle atrophy and improves leg locomotor function to a greater extent than shorter-term treatment in acute stroke patients. This suggests that the management of stroke may be improved with long-term edaravone therapy by providing myoprotective effects that ameliorate functional outcome in the chronic phase.

Literature

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Authors: Hiroaki Naritomi, Hiroshi Moriwaki, Norifumi Metoki, Hiroyuki Nishimura, Yasuto Higashi, Yasumasa Yamamoto, Hiroyuki Yuasa, Hiroshi Oe, Kortaro Tanaka, Kozue Saito, Yasuo Terayama, Tadafumi Oda, Norio Tanahashi, Hisao Kondo
Posted: Drugs R D 2010; 10 (3)
Final Evaluation of the Results of the СТІКс Study (Concomitant Xavron Stroke Therapy)

Abstract. Ischemic stroke remains a pressing problem today. Its pathogenesis consists of a sequential cascade of reactions in the brain, which, in addition to ischemia, are responsible for further damage to brain tissue and slow down the development of compensatory and regenerative mechanisms. Attempts to break the pathological cascade have been going on for decades.

The first promising molecule that demonstrated the potential of a scavenger (cleaner, absorber) of excessive aggressive peroxides in preclinical studies was MCI-186, which is used in clinical practice under the name edaravone. The aim of the study the results of which are presented in this paper was to establish the clinical effects of edaravone (Xavron) as a concomitant therapy of acute ischemic stroke (СТІКс) in real clinical practice.

Background

Effects on the damaging mechanisms of active oxygen radicals in the hyperacute period of stroke (including cases of recanalization therapy) may increase the potential for recovery in the future.

Aim

Assess the impact of radical scavenger use on the long-term effects of stroke in routine clinical practice.

Material and methods

The open case-control study covered 53 stroke departments in Ukraine. 570 patients with ischemic stroke received additional therapy with “Xavron” (edaravone, Yuria-Pharm, Ukraine) – 30 mg twice daily, by infusion, during the hospitalization staying, starting 1 hour after admission (active treatment group, ATG).

430 patients corresponding by age and sex received conventional treatment (control group, CG). The average length of hospital stay was 9.690.19 days. The average score on NIHSS in the ATG was 11.670.26 and 10.930.29 in CG. The number of thrombolysis procedures was 25 (4.4%) in ATG and 30 (6.98%) in CG.

Results. At the time of discharge, the NIHSS score was 6.340,22 in ATG versus 7.460.27 in CG, p=0,001. The mean mRS score was almost the same at discharge (2.660.06 in ATG and 2.770.22 in CG). But after 3 months, the average score of mRS in ATG was significantly lower – 1.871.36 against 2.561.49, p <0.01. Dichotomous comparison of mRS 0-1 vs. 2-6: 42.47% in ATG vs. 32.74% in CG, p = 0.0018.

For mRS 0-2 / 3-6: 65.4% in ATG and 56.1% in CG, p = 0.0029. Positive dynamics of mRS “-1 point” for 90 days was observed in 62.6% of ATG patients against 34.8% in CG: OR = 2.42 (95% CI – 2.42 – 4.17). Hemorrhagic transformation of stroke was observed in 9 (1.84%) ATG patients and 22 (5.67%) CG patients, p = 0.0012. Hospital mortality was 0.7% in ATG and 2% in CG, p = 0.0713.

Conclusions

Additional therapy with free radical scavengers is perspective approach to strengthening the restorative potential after stroke.

Literature

  1. Московко С.П., Кириченко О.В., Руденко Г.С. Протокол відкритого багатоцентрового дослідження «випадок — контроль» щодо безпеки та ефективності використання едаравону (Ксаврон®) у гострому періоді ішемічного інсульту в умовах реальної клінічної практики. Здоров’я України. Спецвипуск «Інсульт». 2020. 1(52). С. 15-16.
  2. Ganesh A., Luengo-Fernandes R., Wharton R.M., Rothwell P.M. Ordinal vs dichotomous analysis of modified Rankin Scale, 5-year outcome, and cost of stroke. Neurology. 2018. 91. e1951-e1960. Doi: 10.1212/WNL.00000000006554.
  3. Chen C., Li M., Lin L., Chen S., Chen Y., Hong L. Clinical effects and safety of edaravone in treatment of acute ischaemic stroke: A meta-analysis of randomized controlled trials. J. Clin. Pharm. Ther. 2021 Feb 27. doi: 10.1111/jcpt.13392.
  4. Московко С.П., Кириченко О.В., Руденко Г.С. Проміжні результати дослідження СТІКс (Супутня Терапія Інсульту Ксавроном) — відкритого багатоцентрового дослідження «випадок — контроль». Журнал неврології ім. Б.М. Маньковського. 2021. Т. 9. № 1.
  5. Watanabe K. How is edaravone effective against acute ischemic stroke and amyotrophic lateral sclerosis? Journal of Clinical Biochemistry and Nutrition. 2018. Vol. 62. Issue 1. P. 20-8. https://doi.org/10.3164/ jcbn.17-622.
Authors: S.P. Moskovko, O.V. Kyrychenko, H.S. Rudenko et al. National Pirogov Memorial Medical University, Vinnytsya, Ukraine
Posted: International Neurological Journal, Volume 17, N 5, 2021
Соchrane Database of Systematic Rewiews. Edaravone for acute ischaemic stroke

Edaravone is a neuroprotective agent, and several studies have suggested that it may be beneficial in acute ischaemic stroke.

Objectives. To assess the efficacy and safety of edaravone for acute ischaemic stroke.

Main results. Authors included three trials. All three included trials were of edaravone plus another treatment compared with the other treatment alone. The dose of edaravone injections in the three trials was the same at 60 mg per day. The course of treatment in all three trials is 14 days. All three trials reported adverse events; there were no differences between the treatment group and the control group. Overall, edaravone appeared to increase the proportion of participants with marked neurological improvement compared with the control group, and the difference was significant (risk ratio (RR) 1.99, 95% confidence interval (CI) 1.60 to 2.49).

Authors: Feng S, Yang Q, Liu M, Li W, Yuan W, Zhang S, Wu B, Li J.
Posted: Соchrane Database of Systematic Rewiews, 2011.