Using tDCS as an Add-On Treatment Prior to FES Therapy in Improving Upper Limb Function in Severe Chronic Stroke Patients: A Randomized Controlled Study

Where the fuck is the protocol located?  I want to bring it to my doctor and therapists attention. They will never find it on their own or even look for it.  Since this is for chronic it could actually help me.
https://www.frontiersin.org/articles/10.3389/fnhum.2018.00233/full?

Nuerjiayi Shaheiwola^1†, Bin Zhang^1†, Jie Jia² and Dingguo Zhang^1*

• ¹State Key Laboratory of Mechanical System and Vibration, Robotics Institute, Shanghai Jiao Tong University, Shanghai, China
• ²Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai, China

Background: Upper limb function recovery is of vital importance for stroke patients. However, it is difficult to get ideal recovery, especially for patients with severe chronic stroke. As the first randomized controlled long-term trial combining bilateral transcranial direct current stimulation (tDCS) and functional electrical stimulation (FES) therapy, this study examined the efficacy of a novel protocol that included applying tDCS as an add-on treatment prior to FES therapy over the course of a 4-week program.

Methods: Thirty subjects with severe chronic stroke were randomized to either Group A (active tDCS+FES) (N = 15) or Group B (sham tDCS+FES) (N = 15). Five assessments including 3 behavioral outcome measurement scales [the Fugl-Meyer scale (cFMA), the Wolf motor function test (WMFT) and the modified Ashworth scale (MAS)], the surface electromyography (sEMG) evaluation and the transcranial magnetic stimulation (TMS) assessment were performed to evaluate subjects before and after the overall therapy.

Results: In Group A, the combined protocol was well tolerated by all patients and induced significant improvements in upper extremity motor abilities in terms of the assessments of cFMA [t₍₁₄₎ = −5.658, p < 0.05], WMFT [t₍₁₄₎ = −3.746, p < 0.05], MAS [t₍₁₄₎ = 5.236, p < 0.05], sEMG and TMS. The results of between-group comparisons showed there was a significant difference between Group A and Group B in terms of the assessments of cFMA [t₍₂₈₎ = 2.223, p < 0.05], WMFT [t₍₂₈₎ = −2.152, p < 0.05] and sEMG [F_{(1, 196)} = 0.918, p < 0.05].

Conclusion: The proposed protocol can facilitate improvements in upper extremity motor abilities in severe chronic stroke patients and is more beneficial than the protocol with FES therapy alone. Our results showed efficacy of the new paradigm with combined intervention in both the central nervous system and the peripheral nervous system.

Trial registration: ChiCTR-ICR-15006108

1. Introduction

As one of the most devastating neurological conditions, stroke results in approximately 5.5 million deaths annually worldwide (Prentice et al., 2004). The worldwide prevalence of stroke survivors was estimated to be 62 million in 2005 and is predicted to reach 77 million by 2030 (Strong et al., 2007). About 65% of the patients experience upper-limb function impairment after 6 months of the stroke onset (Dobkin, 2005). Upper limb function accounts for approximately 60% of the whole body function, indicating that the self-managing ability and independence of patients after stroke mainly depends on upper limb recovery levels (Veerbeek et al., 2011). However, limb motor function recovery usually reaches a plateau 6 months after the onset of the stroke (Stinear, 2010; Stinear et al., 2012). Therefore, it is important to choose effective evidence-based interventions to further promote the recovery of hand function of chronic stroke patients.

Functional electrical stimulation (FES) is a well-studied technique that incorporates electrical stimulation to peripheral sensory and motor nerves with repetitive functional movement of the affected arm (Plonsey and Barr, 2000). Studies that used FES therapy reported significant improvements in upper limb functions of both chronic and acute stroke patients (Popovic et al., 2004, 2005). However, even with the help of regular FES therapy, acute and subacute stroke patients still suffer from a high risk of the upper limb function loss. Central to this problem is the lack of complimentary therapies that can better assist stroke patients in upper limb function recovery.

There is another non-invasive technique called transcranial direct current stimulation (tDCS) which may shed light on the problem (Bindman et al., 1964). The technique is able to induce sustained cortical excitability changes and modify cortical plasticity in the human cortex by shifting the resting potential of neuronal membranes (Nitsche and Paulus, 2001). Anodal tDCS facilitates motor-evoked potentials (MEPs) (Nitsche and Paulus, 2000, 2001) while cathodal tDCS inhibits them in contrast (Nitsche et al., 2003). Related studies have demonstrated the potential effects of tDCS on motor performance of stroke subjects (Fregni et al., 2005; Hummel et al., 2005; Boggio et al., 2007; Hesse et al., 2011). Particularly, cathodal stimulation is used to inhibit the non-lesioned hemisphere as the non-lesioned hemisphere partially overrides the lesioned hemisphere as a result of disturbed interhemispheric competition following stroke (Perez and Cohen, 2009). One study comparing different tDCS electrode montages on stroke subjects showed patients who responded to unilateral tDCS also responded to bilateral motor cortex stimulation, however, the effect of bilateral tDCS (with anodal stimulation in the affected hemisphere vs. cathodal stimulation in the unaffected hemisphere) might differ across patients and stroke characteristics (Mahmoudi et al., 2011).

Since both tDCS and FES therapy have been regarded as promising techniques for stroke rehabilitation, a combination of them may induce significant improvements compared with either one alone. There is some research on simultaneous application of non-invasive cortex stimulation and neuromuscular electrical stimulation on healthy subjects and stroke patients (Rosenkranz et al., 2000; Nitsche et al., 2007; Schabrun et al., 2013). One study evaluating motor task performance of subjects with chronic stroke revealed that combining peripheral nerve stimulation with anodal brain polarization induced superior improvements in performance of a motor task relative to the use of each intervention alone in combination with sham stimulation and training (Celnik et al., 2009). In terms of the combination of tDCS and FES therapy, one recent study by Menezes et al. (2017) assessed the short-term effect of different combinations of tDCS and repetitive peripheral nerve sensory stimulation (RPSS) as add-on treatments to the FES therapy in single sessions (Menezes et al., 2017). However, the long-term efficacy of combining both therapies, to our knowledge, has never been investigated.

In this research, we aimed to examine the long-term efficacy of this combined protocol over upper extremity motor abilities in severe chronic stroke patients. The bilateral montage was used in tDCS intervention. Our hypothesis was that the protocol of combining tDCS as an add-on treatment prior to the FES therapy would be superior to the FES therapy alone in the recovery of upper extremity motor abilities.