Background. Epidural spinal electrical stimulation at the lumbar spinal level evokes rhythmic muscle activation of lower-limb antagonists, attributed to the central pattern generator. However, the ...efficacy of noninvasive spinal stimulation for the activation of lower-limb muscles is not yet clear. This review aimed to analyze the feasibility and efficacy of noninvasive transcutaneous spinal cord stimulation (tSCS) on motor function in individuals with spinal cord injury. Methods. A search for tSCS studies was made of the following databases: PubMed; Cochrane Registry; and Physiotherapy Evidence Database (PEDro). In addition, an inverse manual search of the references cited by the identified articles was carried out. The keywords transcutaneous, non-invasive, electrical stimulation, spinal cord stimulation Mesh term, and spinal cord injury were used. Results. A total of 352 articles were initially screened, of which 13 studies met the inclusion criteria for systematic review. The total participant sample comprised 55 persons with spinal cord injury. All studies with tSCS provided evidence of induced muscle activation in the lower and upper limbs, and applied stimulation at the level of the T11-T12 and C4-C7 interspinous space, respectively. All studies reported an increase in motor response measured by recording surface electromyography, voluntary movement, muscle strength, or function. Conclusions. Although this review highlights tSCS as a feasible therapeutic neuromodulatory strategy to enhance voluntary movement, muscle strength, and function in patients with chronic spinal cord injury, the clinical impact and efficacy of electrode location and current intensity need to be characterized in statistically powered and controlled clinical trials.
The posterior root muscle response (PRM) is a monosynaptic reflex that is evoked by single pulse transcutaneous spinal cord stimulation (tSCS). The main aim of this work was to analyse how body ...weight loading influences PRM reflex threshold measured from several lower limb muscles in healthy participants. PRM reflex responses were evoked with 1‐ms rectangular monophasic pulses applied at an interval of 6 s via a self‐adhesive electrode (9 × 5 cm) at the T11–T12 vertebral level. Surface electromyographic activity of lower limb muscles was recorded during four different conditions, one in decubitus supine (DS) and the other three involving standing at 100%, 50%, and 0% body weight loading (BW). PRM threshold intensity, peak‐to‐peak amplitude, and latency for each muscle were analysed in different conditions study. PRM reflex threshold increased with body weight unloading compared with DS, and the largest change was observed between DS and 0% BW for the proximal muscles and between DS and 50% BW for distal muscles. Peak‐to‐peak amplitude analysis showed only a significant mean decrease of 34.6% (SD 10.4, p = 0.028) in TA and 53.6% (SD 15.1, p = 0.019) in GM muscles between DS and 50% BW. No significant differences were observed for PRM latency. This study has shown that sensorimotor networks can be activated with tSCS in various conditions of body weight unloading. Higher stimulus intensities are necessary to evoke reflex response during standing at 50% body weight loading. These results have practical implications for gait rehabilitation training programmes that include body weight support.
Percutaneous electrical nerve stimulation (PENS) consists of applying an electric current of <1,000 Hz to different neuromuscular structures through acupuncture needles. Currently, there is ...controversy surrounding the effect of PENS on muscle strength in the scientific literature. The main objective was to assess the effect of PENS applied to the median and cubital nerves on the maximum handgrip strength (MHS) compared to sham stimulation, as well as to determine the safety of the intervention. A parallel, randomized, double‐blind controlled trial in a sample of 20 healthy subjects. Participants were randomly allocated in the experimental (n = 10) and control (n = 10) groups. A blinded researcher measured MHS. Measurements of MHS of the dominant hand were taken at four time points: preintervention, immediately postintervention, 24 hr after the intervention, and at a 10‐day follow‐up. A 10‐Hz percutaneous electrical current stimulation was employed. The control group also received the same puncture method but with no electric stimulation. Compared to baseline, the MHS decreased 10.4% (SEM = 3.2, p = .02) in the PENS group at 24 hr postintervention, with no differences observed between baseline and at 10 days postintervention. No changes in grip strength were observed at any time point in the sham group. To sum up, PENS decreased MHS at 24 hr postintervention, which does not persist 10 days after the stimulation. PENS can be considered a safe technique. Trials with larger sample sizes are required to corroborate the findings of this study. Clinical Trials Registration: NCT, NCT04662229, filed on March 12th of 2020.
We have synthesized a family of rhein–huprine hybrids to hit several key targets for Alzheimer’s disease. Biological screening performed in vitro and in Escherichia coli cells has shown that these ...hybrids exhibit potent inhibitory activities against human acetylcholinesterase, butyrylcholinesterase, and BACE-1, dual Aβ42 and tau antiaggregating activity, and brain permeability. Ex vivo studies with the leads (+)- and (−)-7e in brain slices of C57bl6 mice have revealed that they efficiently protect against the Aβ-induced synaptic dysfunction, preventing the loss of synaptic proteins and/or have a positive effect on the induction of long-term potentiation. In vivo studies in APP-PS1 transgenic mice treated ip for 4 weeks with (+)- and (−)-7e have shown a central soluble Aβ lowering effect, accompanied by an increase in the levels of mature amyloid precursor protein (APP). Thus, (+)- and (−)-7e emerge as very promising disease-modifying anti-Alzheimer drug candidates.
Motor impairments are very common in neurological diseases such as multiple sclerosis. Noninvasive brain stimulation could influence the motor function of patients.
The aim of this meta-analysis was ...to evaluate the effectiveness of transcranial direct current stimulation (tDCS) on balance and gait ability in patients with multiple sclerosis. Additionally, a secondary aim was to compare the influence of the stimulation location of tDCS on current effectiveness.
A search was conducted for randomized controlled trials published up to May 2023 comparing the application of tDCS versus a sham or control group. The primary outcome variables were balance and gait ability.
Eleven studies were included in the qualitative analysis, and ten were included in the quantitative analysis, which included 230 patients with multiple sclerosis. The average effect of tDCS on gait functionality was superior to that of the control group (SMD = -0.71; 95% CI, -1.05 to -0.37). However, the overall results of the tDCS vs. sham effect on static balance did not show significant differences between groups (MD = 1.26, 95% CI, -1.31 to 3.82). No significant differences were found when different locations of tDCS were compared.
These results reveal that tDCS is an effective treatment for improving gait ability with a low quality of evidence. However, the application of tDCS has no effect on static balance in patients with multiple sclerosis with very low quality of evidence. Similarly, there seems to be no difference regarding the stimulation area with tDCS.
Transcranial direct-current stimulation (tDCS) is an easy-to-apply, cheap, and safe technique capable of affecting cortical brain activity. However, its effectiveness has not been proven for many ...clinical applications.
The aim of this systematic review was to determine whether the effect of different strategies for gait training in patients with neurological disorders can be enhanced by the combined application of tDCS compared to sham stimulation. Additionally, we attempted to record and analyze tDCS parameters to optimize its efficacy.
A search in Pubmed, PEDro, and Cochrane databases was performed to find randomized clinical trials that combined tDCS with gait training. A chronological filter from 2010 to 2018 was applied and only studies with variables that quantified the gait function were included.
A total of 274 studies were found, of which 25 met the inclusion criteria. Of them, 17 were rejected based on exclusion criteria. Finally, 8 trials were evaluated that included 91 subjects with stroke, 57 suffering from Parkinson's disease, and 39 with spinal cord injury. Four of the eight assessed studies did not report improved outcomes for any of its variables compared to the placebo treatment.
There are no conclusive results that confirm that tDCS can enhance the effect of the different strategies for gait training. Further research for specific pathologies, with larger sample sizes and adequate follow-up periods, are required to optimize the existing protocols for applying tDCS.
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method able to modulate neuronal activity after stroke. The aim of this systematic review was to determine if tDCS ...combined with robotic therapy (RT) improves limb function after stroke when compared to RT alone.
A search for randomized controlled trials (RCTs) published prior to July 15, 2021 was performed. The main outcome was function assessed with the Fugl-Meyer motor assessment for upper extremities (FM/ue) and 10-m walking test (10MWT) for the lower limbs. As secondary outcomes, strength was assessed with the Motricity Index (MI) or Medical Research Council scale (MRC), spasticity with the modified Ashworth scale (MAS), functional independence with the Barthel Index (BI), and kinematic parameters.
Ten studies were included for analysis (n = 368 enrolled participants). The results showed a non-significant effect for tDCS combined with RT to improve upper limb function standardized mean difference (SMD) = - 0.12; 95% confidence interval (CI): - 0.35-0.11). However, a positive effect of the combined therapy was observed in the lower limb function (SMD = 0.48; 95% CI: - 0.15-1.12). Significant results favouring tDCS combined with RT were not found in strength (SMD = - 0.15; 95% CI: - 0.4-0.1), spasticity mean difference (MD) = - 0.15; 95% CI: - 0.8-0.5), functional independence (MD = 2.5; 95% CI: - 1.9-6.9) or velocity of movement (SMD = 0.06; 95% CI: - 0.3-0.5) with a "moderate" or "low" recommendation level according to the GRADE guidelines.
Current findings suggest that tDCS combined with RT does not improve upper limb function, strength, spasticity, functional independence or velocity of movement after stroke. However, tDCS may enhance the effects of RT alone for lower limb function. tDCS parameters and the stage or type of stroke injury could be crucial factors that determine the effectiveness of this therapy.
The intensity used during transcutaneous electrical nerve stimulation (TENS) in both, clinical practice and research studies, is often based on subjective commands such as "strong but comfortable ...sensation". There is no consensus regarding the effectiveness dose of TENS. The objective was to determine the difference in the effect of spinal TENS on soleus H-reflex modulation when applied by two therapists instructed to apply the stimulation at a "strong but comfortable" intensity. Twenty healthy volunteers divided into two groups: Therapist 1 (n = 10) and Therapist 2 (n = 10). Both therapist applied spinal TENS and sham stimulation at the T10-12 spinal level for 40min in random order to each subject, at an intensity designed to produce a "strong but comfortable" sensation. To avoid habituation, the intensity was adjusted every 2min. Soleus H-reflex was recorded before, during, and 10min after TENS by an observer blinded to the stimulus applied. Despite the instruction to apply TENS at a "strong comfortable" level, a significant difference in current density was identified: Therapist 1 (0.67mA/cm2, SD 0.54) applied more than Therapist 2 (0.53mA/cm2, SD 0.57; p<0.001) at the onset of the intervention. Maximal peak-to-peak H-reflex amplitude was inhibited significantly more 10min following TENS applied by Therapist 1 (-0.15mV, SD 0.16) compared with Therapist 2 (0.04mV, SD 0.16; p = 0.03). Furthermore, current density significantly correlated with the inhibitory effect on peak-to-peak Soleus H-reflex amplitude 10 min after stimulation (Rho = -0.38; p = 0.04). TENS intensity dosage by the therapist based on the subjective perception of the participants alone is unreliable and requires objective standardization. In addition, higher current density TENS produced greater inhibition of the Soleus H-reflex.
Unmodulated high-frequency alternating currents (HFAC) are employed for producing peripheral nerves block. HFAC have been applied in humans with frequencies up to 20 kHz, whether transcutaneously, ...percutaneously, or
surgically-implanted electrodes. The aim of this study was to assess the effect of percutaneous HFAC, applied with ultrasound-guided needles at 30 kHz, on the sensory-motor nerve conduction of healthy volunteers.
A parallel, double-blind, randomized clinical trial with a placebo control was conducted. Percutaneous HFAC at 30 kHz or sham stimulation was applied
ultrasound-guided needles in 48 healthy volunteers (
= 24 in each group) for 20 min. The assessed outcome variables were pressure pain threshold (PPT), mechanical detection threshold (MDT), maximal finger flexion strength (MFFS), antidromic sensory nerve action potential (SNAP), hand temperature, and subjective sensations by the participants. The measurements were recorded pre-intervention, during the stimulation (at 15 min), immediately post-intervention (at 20 min), and 15 min after the end of treatment.
The PPT increased in the active group compared with sham stimulation, both during the intervention 14.7%; 95% confidence interval (CI): 4.4-25.0, immediately post-intervention (16.9%; 95% CI: -7.2-26.5), and 15 min after the end of the stimulation (14.3%; 95% CI: 4.4-24.3) (
< 0.01). The proportion of participants who reported feelings of numbness and heaviness was significantly higher in the active group (46 and 50%, respectively) than in the sham group (8 and 18%, respectively) (
< 0.05). No intergroup differences were observed in the remaining outcome variables. No unexpected adverse effects derived from the electrical stimulation were reported.
Percutaneous stimulation with HFAC at 30 kHz applied to the median nerve increased the PPT and subjective perception of numbness and heaviness. Future research should evaluate its potential therapeutic effect in people with pain.
https://clinicaltrials.gov/ct2/show/NCT04884932, identifier NCT04884932.
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