Combine Mirror Therapy and tDCS on CPSP
Condition: Stroke; Pain
Study type: Interventional

Summary: 
      Central poststroke pain (CPSP) refers to the symptom of pain arising after a stroke. Patients
      with CPSP often complain of various painful or unpleasant sensation. Feelings of pain may
      interfere with sleep and hugely affect the patients' quality of life. Non-invasive brain
      stimulation, such as transcranial direct current stimulation (tDCS), is an emerging
      nonpharmacological treatment and has been shown to have promising pain reduction effects for
      patients with CPSP. Mirror therapy (MT), on the other hand, is a contemporary approach that
      has often been used to facilitate upper extremity motor recovery in patients with stroke. MT
      has been shown to be effective in ameliorating sensory deficits and reducing shoulder pain.
      To date, no study has determined whether combining MT with tDCS could reduce pain in patients
      with CPSP. The goal of this study is to determine the effect of combining MT and tDCS on
      pain, sensation, motor function, and quality of life in people with CPSP.

      Forty-five patients with CPSP will be randomly allocated to one of the 3 groups: combining MT
      with tDCS (MT+tDCS) group, MT with sham tDCS (MT+s-tDCS) group, and sham MT with tDCS
      (s-MT+tDCS) group. The participants in all groups will receive intervention 30 minutes/day, 3
      days/ week, for 3 weeks. The participants in the MT+tDCS group will receive tDCS applied
      simultaneously with MT for 20 minutes. For the following 10 minutes, the tDCS will be turned
      off while the electrodes will be kept on the scalp, and the participants will continue with
      MT. For the MT+s-tDCS group, same tDCS procedures will be applied to the participants except
      that the stimulator will be turned off within 30 seconds. As for the s-MT+tDCS group, the
      participants will receive the same tDCS procedure as the MT+tDCS group while a sham MT
      condition will be applied. Clinical and neurophysiological assessments will be conducted
      before the treatment (pretest), after 3 weeks of treatment (post-test), and 1 month after the
      treatment (follow-up test). The assessments will be performed by research assistants who will
      be blinded to the group allocation of the participants. Mix-model Group × Time repeated
      measures ANOVAs will be used to determine the intervention effects of the 3 groups.
    

Detailed description: 
      Central poststroke pain (CPSP) refers to the symptom of pain arising after a stroke. Patients
      with CPSP often complain of various painful or unpleasant sensation.The feelings of pain may
      interfere with sleep and hugely affect the patients' quality of life. Additionally, CPSP may
      compromise rehabilitation and hinder movement recovery after stroke.

      Non-invasive brain stimulation, such as repetitive transcranial magnetic stimulation (rTMS)
      or transcranial direct current stimulation (tDCS), is an emerging nonpharmacological
      treatment and has been shown to have promising pain reduction effects for patients with CPSP.
      Compared with rTMS, tDCS is less expensive, easier to implement, and requires less labor
      work. Via a weak current flow, tDCS can modulate neuronal excitability in a polarity-specific
      manner. Anodal electrode of tDCS can depolarize the membrane potential and enhance
      corticomotor excitability, while cathodal electrode could reduce neuronal excitability.

      Mirror therapy (MT) is a contemporary approach that has often been used to facilitate upper
      extremity motor recovery in patients with stroke. In addition to motor functions, MT has also
      been shown to be effective in ameliorating sensory deficits and reducing shoulder pain or
      reflex sympathetic dystrophy. Despite the evidence on the benefits of MT on sensation and
      shoulder pain, very few study specifically investigates the effect of MT on CPSP. One single
      case study reported benefits of MT on CPSP. A larger sample size is warranted to determine
      whether MT could effectively reduce CPSP. Furthermore, combining MT with non-invasive
      modulation tool may further intensify sensorimotor reorganization and reduce pain. Therefore,
      this proposed study aims to determine whether combining MT with tDCS could reduce pain in
      patients with CPSP.

      The goal of this study is to determine the effect of combining MT and tDCS on pain,
      sensation, motor function, and quality of life in people with CPSP. It is hypothesized that
      compared with the single treatment groups, combining MT and tDCS will induce greater
      improvement in pain, motor function, and quality of life in patients with CPSP.

      Methods: This study plans to recruit 45 patients with CPSP. The proposed study is designed to
      be a randomized controlled trial with pretest, posttest, and 1-month follow-up test. After
      signing the informed consent, eligible participants will be randomly allocated to one of the
      3 groups: combining MT with tDCS (MT+tDCS) group, MT with sham tDCS (MT+s-tDCS) group, and
      sham MT with tDCS (s-MT+tDCS) group.

      Clinical and neurophysiological assessments will be conducted before the treatment (pretest),
      after 3 weeks of treatment (post-test), and 1 month after the treatment (follow-up test). The
      assessments will be performed by research assistants who will be blinded to the group
      allocation of the participants.

      Throughout the study, all participants will be required to keep their regular treatment
      regimen, and the current intervention will be an add on treatment for the patients. The
      participants in all groups will receive intervention 30 minutes/day, 3 days/ week, for 3
      weeks resulting in 9 training sessions. The participants in the MT+tDCS group will receive
      tDCS applied simultaneously with MT for 20 minutes. For the following 10 minutes, the tDCS
      will be turned off while the electrodes will be kept on the scalp, and the participants will
      continue with MT. For the MT+s-tDCS group, same tDCS procedures will be applied to the
      participants except that the stimulator will be turned off within 30 seconds. The
      participants will perform MT with sham tDCS. As for the s-MT+tDCS group, the participants
      will receive the same tDCS procedure as the MT+tDCS group while a sham MT condition will be
      applied.

      The outcome measures of this study will include the Mini-Mental Screening Examination (MMSE),
      subjective pain, pressure pain threshold, Neuropathic pain symptom inventory (NPSI),
      Quantitative sensory test (QST), Fugl-Mayer Assessment-Upper Extremity (UE-FMA), Box and
      block test (BBT), Motor activity log (MAL), WHOQOL-BREF Taiwan Version, and Transcranial
      magnetic stimulation (TMS) assessment, Somatosensory evoked potentials (SSEP), Nerve
      conduction velocity (NCV). The mix-model Group × Time repeated measures ANOVAs will be used
      to determine the intervention effects of the 3 groups.
    

Intervention name(s): mirror therapy; tDCS; sham mirror therapy; sham tDCS
Intervention type(s): Behavioral; Device; Behavioral; Device
Intervention description(s): a mirror box will be placed in front of the participants with the mirror reflection side toward the non-paretic limb. The paretic arm will be placed behind the mirror, and the mirror box will block the vision of the paretic limb. Through this method, the patients can only view the movement of the non-paretic limb and its mirror reflection from the mirror. The participants will be instructed to move or perform functional tasks with their non-paretic limb and look at the mirror reflection of the non-paretic limb and mentally imagine that it is the paretic arm moving. At the same time, the participants will be encouraged to move the paretic arm along with the mirror reflection of the non-paretic arm. Activities practice during MT will include gross motor movements, fine motor movements, and functional tasks.; The tDCS will be delivered by a DC-stimulator (Soterix Medical Inc, New York, USA) through 2 saline-soaked surface sponge electrodes (anodal electrode size: 25 cm2; cathode electrode size: 25 cm2). The anodal electrode will be placed over the ipsilesional M1 while the cathodal electrode will be placed over the contralesional M1. The stimulation intensity will be ramped up to 2mA in 15 seconds, and maintained at 2mA throughout the 20-minute stimulation for the MT+tDCS group.; For the sham MT (s-MT) condition, the same mirror box will be used except that the mirror side will be made blurred to view; thus, the participants will not be able to view the mirror reflection of the paretic limb. The participants will perform the same activities as the real MT condition.; For the sham tDCS group, the electrodes will be placed on the brain regions as the real tDCS group. The intensity will first be ramped up to 2mA within 15 seconds and then the stimulator will be turned off gradually within the next 30 seconds.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 3 groups of different interventions
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: central poststroke pain; mirror therapy; transcranial direct current stimulation; transcranial magnetic stimulation