Brain Electrical Stimulation to Enhance Recovery After Stroke

OBJECTIVES

There is no universally accepted strategy to promote recovery of motor function after stroke, the main cause of long-term disability among adults. Neurorehabilitation contributes to recovery during the first days to weeks after stroke and later decelerates. Therefore, it is desirable to develop strategies to enhance rehabilitative effects on motor recovery particularly in the early phase after stroke in this patient group. We have recently demonstrated that cortical stimulation in the form of TMS enhances the beneficial effects of motor training and cortical plasticity in healthy volunteers and that tDCS (another noninvasive more comfortable stimulating technique than TMS transiently improves functional motor skills of the paretic hand of chronic stroke patients in the absence of training. Given the paucity of strategies available to enhance neurorehabilitation after stroke, it is now crucial to determine if tDCS can enhance the beneficial effects of customarily used rehabilitative treatment. tDCS has been used in several hundred subjects worldwide and in approximately 9 stroke patients, 15 Parkinson's disease patients and 15 healthy volunteers in our lab in the absence of undesirable side effects.

In addition to the above objectives, we will also apply functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) techniques to determine the extent of changes in neural responses and functional shift in cortical representations/reorganization as a result of the proposed intervention strategies. fMRI as a measure is important in understanding changes in brain activation prior to, during, and after motor recovery and the effects of tDCS and the rehabilitative treatment strategies under investigation. Integrating TMS together with fMRI studies will provide crucial information on the functional role of brain regions activated in neuroimaging studies in association with functional recovery.

STUDY POPULATION

We plan to study 120 patients with a single cortical or subcortical subacute stroke. Thirty healthy volunteers and a sub-group of 30 patients from the 120 patient population will also be recruited in the fMRI and TMS part of the study. The reason for including 30 patients in the fMRI and TMS components of the study is that it is anticipated that not all the 120 patients recruited in the initial study (i.e., the tDCS and therapeutic intervention phase) may be able to perform the tasks required for the fMRI part of the study and also satisfy the Exclusion criteria for fMRI scans. In addition, based on previous studies and preliminary fMRI power analysis, we estimate that 30 patients is likely to be sufficient to provide a representative sample of the patient group for the testing of the hypotheses stated in the protocol. Thirty healthy volunteers are necessary for the fMRI and TMS components of the study in order to obtain normative data for the TMS and fMRI components of the investigation. They will have the multiple number of TMS and fMRI sessions as patients in order to obtain descriptive information on the variability of these measures in both groups.

DESIGN

The purpose of this protocol is to test the hypothesis that tDCS applied in combination with customary rehabilitative training as used in the community (RT) will enhance motor recovery 3 months after admission relative to placebo and RT, and that functional recovery is associated with changes in cortical excitability in the ipsilesional primary motor cortex (M1) and dorsal pre-motor cortex. The tDCS part of the study will be done at the NRH (where is being evaluated in parallel with the NINDS review process). Patients will be included in the protocol as soon as they are admitted to the NRH for RT (usually 3-10 days after the ictal event). Patients, who are eligible for the protocol will be randomized in one of the two study arms: RT + tDCS or RT + placebo stimulation. In both study arms patients will take part in daily customary RT procedures. We will record the specific rehabilitative therapy received by the patient. In the tDCS study arm, patients will receive tDCS of the motor cortex associated with RT every other day for the time of the inpatient stay (14 days). Placebo will be implemented in the same way and with the same stimulating equipment in place as tDCS. Patient and therapist (who will provide treatment and determine the primary outcome measure) will not be aware of arm participation (double-blind study design).

Normal volunteers will be recruited only for the fMRI and TMS part of the study which will be carried out at the NIH. They will be screened based on the criteria listed in the protocol and receive a neurological exam to determine their qualification for the proposed studies.

OUTCOME MEASURES

Primary outcome measure will be the Jebsen-Tailor-Test (JTT), a test measuring the functional abilities of the hand in daily living activities. Secondary outcome measures will include the Wolf Motor Function Test (WMFT), the Fugl-Meyer-scale (FMS), the MRC scale, the Abilhand scale (AHS), Barthel Index, Ashworth-Spasticity scale (ASS), and grating orientation task (GOT) and the NIH stroke scale. For the fMRI and TMS studies, changes in BOLD (blood oxygenation level dependent) response and delayed reaction time will be the outcome measures.