Transcranial Direct Current Stimulation (tDCS) in Acute Stroke Patients

In a murine model, it has been demonstrated that a cathodic polarization of cortical surface with intensities of 30 µA and higher blocked the spreading depression completely. There is no study demonstrating this in stroke patients. tDCS is a powerful tool to modulate the excitability of motor areas. Cathodal tDCS induces a decrease of 30-50% of motor evoked potentials amplitudes. In another study, cathodal stimulation compared with sham induced a prolonged decrease of tactile discrimination, while sham stimulation did not. In our study, cathodal stimulation will be delivered over lateral motor area (C3 or C4, 10-20 system) using an intensity of 2 mA, in order to assess if an inhibition, a hyperpolarization of the middle cerebral artery stroke ischemic penumbra could be obtained.

tDCS is characterized by an excellent safety profile. tDCS studies in patients were performed with intensities comprised between 1 and 2 mA. Safety for these intensities has been demonstrated. Minor tDCS adverse effects in healthy humans and patients with varying neurological disorders were reported. These tDCS studies were performed for a wide range of neurological and psychiatric conditions including pain, depression, Parkinson disease and stroke rehabilitation. Mild tingling sensation, moderate fatigue, itching sensation under the stimulating electrodes, headache were described. Tinnitus was also reported.

In human studies, durations of tDCS stimulation are generally comprised between 3 and 40 minutes, in iterative sessions. In our study, tDCS will be begun less than 4h30 after the beginning of symptoms. Studies with murine stroke models demonstrated that cathodal tDCS starting 45 minutes after middle cerebral artery occlusion and lasting 6 hours had a neuroprotective effect reducing the infarct volume by 30% (20% in the group 4 hours of duration, compared to sham). Based on these data, in our study, tDCS will be delivered 20 minutes per hour, during 6 hours. Usual neurovascular cares (IV thrombolysis, thrombectomy if indicated) will be unchanged.

Some simulation studies have demonstrated that approximately half of the current injected during tDCS is shunted through the scalp. Using stimulating currents of 2 mA, the magnitude of the current density in relevant regions of the brain is of the order of 0.1 A/m2, corresponding to an electric field of 0.22 V/m. Induced skin burns are rare. Skin burns are preceded by a painful sensation. Saline-soaked sponges placed under the electrodes have to remain moist in order to avoid these burns. In our study, patients will be questioned about the tolerance of tDCS stimulation each hour. Impedance values of the tDCS electrodes will be checked each hour.

A cephalic electrode montage has been chosen. A setup with M1 placement of the target electrode (C3 or C4, 10-20 system) and an extra-cephalic placement of the return electrode (shoulder) leads to a twofold to threefold higher electric field in the brainstem as compared to the more commonly used cephalic setup with the target electrode over M1, and the return electrode over the contralateral fronto-polar area (FP2 or FP1, 10-20 system). Reported cerebral autoregulation changes may have been mediated via stimulation of brainstem autonomic centers. The use of a cephalic return electrode montage is thus recommended. Accordingly to these recommendations, in our study, the two electrodes are in a cephalic position: C3 or C4 and FP2 or FP1 (10-20 system).