Brain Electrical Stimulation to Enhance Recovery After Stroke
Condition: Stroke
MeSH terms: Stroke
Study type: Observational

Summary: 
      This study will examine whether brain stimulation using transcranial direct current
      stimulation (tDCS) in stroke patients undergoing rehabilitation therapy can help patients
      recover strength and motor function more than rehabilitation therapy alone. For tDCS, two
      small metal disks (electrodes) attached to wires are placed on small cotton pads and taped to
      the subject's head, one on the forehead above the eye and the other on the top of the head.
      The electrodes deliver a brief electrical current that stimulates the cortex, the part of the
      brain responsible for motor function.

      Adult patients who have weakness on one side of their body as a result of a stroke occurred
      within the last 15 days may be eligible for this study. NIH is not directly recruiting
      patients for this study. Patients will be selected through the National Rehabilitation
      Hospital (NRH) Research Center personnel in Washington, DC, from patients under treatment at
      that facilitiy. Candidates are screened with a physical and neurologic examination, a review
      of tests done on admission to NRH, and a magnetic resonance imaging (MRI) scan, if one has
      not been done since the stroke. MRI uses a strong magnetic field and radio waves to obtain
      images of the brain. The MRI scanner is a metal cylinder surrounded by a strong magnetic
      field. During the MRI, the patient lies on a table that can slide in and out of the cylinder.
      Scanning time for this study takes about 30 to 45 minutes.

      Participants are randomly assigned to receive tDCS or placebo stimulation, along with
      rehabilitation therapy, for 2 to 3 weeks, depending on the patient's length of stay at the
      NRH. For the placebo stimulation, electrodes are placed on the patient's scalp as with tDCS,
      but no current is delivered. Before and after each rehabilitation session with electrodes,
      patients undergo Jebsen Taylor motor testing, in which they are asked to lift small objects,
      turn cards, use a spoon, stack checkers, and lift cans as fast as they can.

      On the day of discharge, patients have physical and neurological examinations and the motor
      function tests described below. The motor tests are repeated, along with standard care and a
      review of their health status, during outpatient follow-up visits scheduled at 3, and 12
      months. The motor tests are:

        -  Wolf motor function test - Patients are asked to raise a forearm on a table, on a box,
           to reach across a table, push a sandbag, place a hand on the table, pull a weight, lift
           a can, pick up a pencil, pick up a paper clip, stack checkers, flip cards, use a key,
           fold a towel, and pick up a basket.

        -  Barthel index - Patients are timed for the speed with which they perform certain tasks,
           such as feeding, grooming, or moving a wheelchair.

        -  Abilhand questionnaire - Patients answer questions about how they perform routine daily
           activities.

        -  GOT test of tactile discrimination - Patients describe objects they feel with their
           hand.

        -  Ashworth spasticity scale - A medical staff person moves the patient's arm back and
           forth to see how stiff it is.
    

Detailed description: 
      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.
    

Keywords: Direct Current Stimulation; Cortical Reorganization; Rehabilitation; Acute Stroke; Stroke