Prevention of post-stroke disuse muscle atrophy with a free radical scavenger

In spite of appropriate treatment in the acute phase of stroke, quite a few patients with hemiparetic stroke become disabled and stay in a wheelchair or bedridden state in the chronic phase. In stroke patients, gait dysfunction results mainly from severe hemiparesis due to ischemic damage to the motor neuron tract and partly from disuse muscle atrophy in paretic and nonparetic legs. Disuse muscle atrophy occurs even in healthy subjects as early as 4 days after bed rest immobilization and progresses further correlating with the duration of immobilization. Although detailed mechanisms of disuse muscle atrophy remain unclear, free radical scavengers are known to play an important role in the development of disuse muscle atrophy. One of the neuroprotective agents, edaravone, a free radical scavenger, succeeded in proving clinical usefulness in a phase III clinical trial in Japan. In this trial, stroke patients were administered edaravone for 14 days consecutively. The results of the edaravone trial are taken to indicate that long-term administration of a free radical scavenger may prevent disuse atrophy thereby improving functional outcome. We performed a randomized pilot study in hemiparetic stroke patients to test the validity of this view. Acute stroke patients were randomly allocated to two groups, one receiving edaravone for 3 days (short-term group) and the other for 10-14 days (long-term group). At 3 months after stroke, the grade of femoral muscle atrophy was significantly milder and the maximum walking speed was significantly faster in the long-term group than in the short-term group. The study suggests that long-term administration of a free radical scavenger may prevent the development of leg disuse atrophy thereby ameliorating locomotor function. Attention should be paid to myoprotective drug therapy in acute stroke, since it may be easier and clinically more effective than neuroprotective therapy from the viewpoint of functional prognosis.