SUMMARY1. In ten normal volunteers, a transcranial magnetic or electric stimulus that was subthreshold for evoking an EMG response in relaxed muscles was used to condition responses evoked by a later, suprathreshold magnetic or electric test shock. In most experiments the test stimulus was given to the lateral part of the motor strip in order to evoke EMG responses in the first dorsal interosseous muscle (FDI).2. A magnetic conditioning stimulus over the hand area of cortex could suppress responses produced in the relaxed FDI by a suprathreshold magnetic test stimulus at interstimulus intervals of 1-6 ms. At interstimulus intervals of 10 and 15 ms, the test response was facilitated.3. Using a focal magnetic stimulus we explored the effects of moving the conditioning stimulus to different scalp locations while maintaining the magnetic test coil at one site. If the conditioning coil was moved anterior or posterior to the motor strip there was less suppression of test responses in the FDI. In contrast, stimulation at the vertex could suppress FDI responses by an amount comparable to that seen with stimulation over the hand area. With the positions of the two coils reversed, conditioning stimuli over the hand area suppressed responses evoked in leg muscles by vertex test shocks.4. The intensity of both conditioning and test shocks influenced the amount of suppression. Small test responses were more readily suppressed than large responses. The best suppression was seen with small conditioning stimuli (0 7-0 9 times motor threshold in relaxed muscle); increasing the intensity to motor threshold or above resulted in less suppression or even facilitation.5. Two experiments suggested that the suppression was produced by an action * Present address: Third Department of Internal Medicine, Division of Neurology, Yamagata University, School of Medicine, 2-2-2 Iida-Nishi, Yamagata City 990-23, Yamagata, Japan.

SUMMARY1. Using two magnetic stimulators, we investigated the effect of a conditioning magnetic stimulus over the motor cortex of one hemisphere on the size of EMG responses evoked in the first dorsal interosseous (FDI) muscle by a magnetic test stimulus given over the opposite hemisphere.2. A single conditioning shock to one hemisphere produced inhibition of the test response evoked from the opposite hemisphere when the conditioning-test interval was 5-6 ms or longer. We shall refer to this as interhemispheric inhibition. However, the minimum latency of inhibition observed using surface EMG responses may have underestimated the true interhemispheric conduction time. Single motor unit studies suggested values 4-7 ms longer than the minimum interval observed with surface EMG.3. Interhemispheric inhibition was seen when the test muscle was active or relaxed. Increasing the intensity of the conditioning stimulus increased the duration of inhibition: increasing the intensity of the test stimulus reduced the depth of inhibition.4. The conditioning coil had to be placed on the appropriate area of scalp for inhibition to occur. The effect of the conditioning stimulus was maximal when it was applied over the hand area of motor cortex, and decreased when the stimulus was moved medial or lateral to that point. A. FERBERT AND OTHERS 6. When the test muscle was relaxed, the amount of interhemispheric inhibition could be increased slightly by voluntary contraction of the muscles in the hand contralateral to the conditioning hemisphere. This effect disappeared if the test muscle was held active throughout the experiment.7. Magnetic conditioning stimuli over one hemisphere were also capable of affecting on-going voluntary EMG activity in the ipsilateral FDI. Inhibition began 10-15 ms after the minimum corticospinal conduction time to the muscle, and lasted for about 30 ms. The depth of inhibition was approximately proportional to the level of on-going EMG. A similar period of inhibition was also observed in the forearm flexor muscles, but in biceps it was less clear and sometimes preceded by excitation.8. The interhemispheric inhibition described in these experiments is probably produced via a transcallosal pathway.

An open angiography-based, dose rate escalation study on the effect of intravenous infusion of recombinant tissue plasminogen activator (rt-PA) on cerebral arterial recanalization in patients with acute focal cerebral ischemia was performed at 16 centers. Arterial occlusions consistent with acute ischemia in the carotid or vertebrobasilar territory in the absence of detectable intracerebral hemorrhage were prerequisites for treatment. After the 60-minute rt-PA infusion, arterial perfusion was assessed by repeat angiography and computed tomography scans were performed at 24 hours to assess hemorrhagic transformation. Of 139 patients with symptoms of focal ischemia, 80.6% (112) had complete occlusion of the primary vessel at a mean of 5.4 +/- 1.7 hours after symptom onset. No dose rate response of cerebral arterial recanalization was observed in 93 patients who completed the rt-PA infusion. Middle cerebral artery division (M2) and branch (M3) occlusions were more likely to undergo recanalization by 60 minutes than were internal carotid artery occlusions. Hemorrhagic infarction occurred in 20.2% and parenchymatous hematoma in 10.6% of patients over all dose rates, while neurological worsening accompanied hemorrhagic transformation (hemorrhagic infarction and parenchymatous hematoma) in 9.6% of patients. All findings were within prospective safety guidelines. No dose rate correlation with hemorrhagic infarction, parenchymatous hematoma, or both was seen. Hemorrhagic transformation occurred significantly more frequently in patients receiving treatment at least 6 hours after symptom onset. No relationship between hemorrhagic transformation and recanalization was observed. This study indicates that site of occlusion, time to recanalization, and time to treatment are important variables in acute stroke intervention with this agent.

In this retrospective analysis we report our treatment experience in 65 consecutive patients with clinical signs of severe brainstem ischemia with angiographically demonstrated thrombotic vertebrobasilar artery occlusions who received either local intra-arterial thrombolytic therapy (urokinase or streptokinase) (43 patients) or conventional therapy (antiplatelet agents or anticoagulants) (22 patients). We analyzed the data with respect to cerebral artery occlusion patterns, posttreatment arterial recanalization, and the clinical categories of favorable/unfavorable outcome and survival/death. In subgroup analyses, recanalization in patients who received thrombolytic therapy correlated significantly with clinical outcome; in 19 of 43 patients, recanalization was demonstrated angiographically, while in 24 patients the occlusion persisted. All patients without recanalization died, but 14 of the 19 patients displaying recanalization survived (p = 0.000007), 10 with a favorable clinical outcome. Only three of the 22 patients who received conventional therapy survived, all with a moderate clinical deficit. When we compared the treatment groups, highly significant differences in both outcome quality (p = 0.017) and survival (p = 0.0005) were found to depend on establishing recanalization. Our data support the concept that technically successful thrombolysis of vertebrobasilar artery occlusions is associated with beneficial clinical outcome.