Using Repetitive Transcranial Magnetic Stimulation (rTMS) in the Rehabilitation of Chronic Spatial Neglect After Stroke
Condition: Cerebrovascular Disorders; Cerebral Stroke; VISIO-spatial Neglect; VISUO-spatial Extinction
MeSH terms: Stroke; Cerebrovascular Disorders; Perceptual Disorders
Study type: Interventional
Phase: Phase 3

Summary: 
      Visuospatial neglect is a common neurological symptom which appears following strokes on
      regions of the right hemisphere of the brain. It affects patient's self representation and
      awareness of the space, impairing functional rehabilitation and adaptation back to a normal
      life. The primary purpose of this protocol is to assess the impact of 10 daily sessions of a
      non-invasive brain stimulation technique, low frequency repetitive Transcranial Magnetic
      Stimulation (rTMS), applied on the intact hemisphere of the brain to treat post stroke
      visuospatial neglect at the chronic stage. The hypothesis is that a regime of real but not
      sham rTMS on the left posterior parietal cortex of the brain will long-lastingly ameliorate
      visuospatial neglect in stroke patients as revealed by clinical paper-and-pencil and
      computer-based tests assessing search, detection and discrimination of stimuli presented in
      different areas of the visual field.
    

Detailed description: 
      Scientific aims and goals:

      The long-term goal aim of this application is to provide evidence of the role of a
      non-invasive neuromodulation technique such as rTMS in the treatment of chronic neurological
      sequels generated after strokes in human patients. Such interventions are based in an "at
      will" modulation the level of activity in intact regions, resulting in an enhancement of
      excitatory projections or the suppression of inhibitory influences driven through spared
      connectivity. They result in activity increases of the stroke surviving neurons, allowing the
      re-emergence of function after brain damage. Such principles can be applied to different
      sorts of neurological sequels for which the underlying connectivity and its post-stroke
      status is well known. In this specific project, we propose the use of low frequency rTMS on
      the intact left posterior parietal cortex (in the intraparietal sulcus, IPS) to improve the
      symptoms of visuospatial neglect derived form right stroke injuries including the posterior
      parietal cortex. Such project is based in the interhemispheric rivalry hypothesis, according
      to which, spatial neglect is in part caused by the over inhibition exerted from the intact
      left parietal cortex onto the injured left homologue regions, which are mediated by
      well-known overall inhibitory transcallosal projections between the left and the right
      hemispheres. According to this hypothesis and preliminary data, the reduction of the left
      parietal disinhibition should result into a lesser degree of suppression exerted by the
      intact left hemisphere sites onto the right injured parietal areas, process which will along
      the emergence of activity.In this context, we defined a primary aim accompanied by two
      secondary aims, which will be tackled in parallel:Primary AIMS AIM1: To assess the effects of
      repetitive Transcranial Magnetic Stimulation (rTMS) in the treatment of chronic visuospatial
      neglect generated by stroke Secondary AIMS AIM 2: To assess the durability of such a recovery
      over time once the treatment is completed and discontinued AIM 3: To further assess the
      safety of such therapeutic approach based in the deactivation of an intact -but hyperexcited
      region- holding connectivity with the damaged area.

      Evaluation criteria Main criteria -Changes in the Spatial Bias Compound Score (SBCS) between
      pre (baseline) and post 10 days of rTMS treatment Such score is calculated on the basis of
      the result of 4 subtests which include: (1) bells cancellation task, (2) a copy of the
      GAINOTTI figure, (3) identification of overlapping figures, and (4) line bisection, according
      to the following formula (SBCS=λ=ln(XR/XL), considering the identification or copying of
      elements presented on the right or the left visual fields of the patient. The subtests of the
      SBCS will be also individually assessed and followed.

      Secondary criteria

        1. Efficacy criteria

        2. Safety criteria

        3. Predictive factors assessmentStudy population and duration of studyWe will study a
           population of stroke patients with chronic signs of hemispatial neglect with at least 3
           months of evolution (n=148, 2 groups of 74 patients) recruited across 48 months at an
           approximate rate of 37 patients /year.
    

Intervention name(s): Real rTMS; Sham rTMS
Intervention type(s): Device; Device
Intervention description(s): Transcranial Magnetic Stimulation, in a low frequency (1 Hz) continuous train of 20 minutes (1200 pulses); two TMS coils will be used: a passive one which is placed flat on top of the "actively" targeted region which remains unplugged and generates a continuous scalp tactile sensation, and an active one located at a prudential distance from the scalp, which will deliver active pulses and its accompanying sensations
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Stroke; Visuospatial neglect; Visuospatial extinction; Transcranial Magnetic Stimulation (TMS); Non-invasive brain stimulation; Neuromodulation; Brain parietal cortex; Neurological sequels; Cognitive rehabilitation