Feasibility and efficacy of an early sensory-motor rehabilitation program on hand function in patients with stroke: a pilot, single-subject experimental design.

OBJECTIVE: Hand and upper limb functional impairments following stroke lead to limitations in performing activities of daily living. We aimed to investigate feasibility and efficacy of an early sensory-motor rehabilitation program on hand and upper limb function in patients with acute stroke. DESIGN: A pilot, single-subject experimental, A-B-A study. SETTING: Stroke unit of an educational hospital and an outpatient occupational therapy clinic. PARTICIPANTS: A convenience sample including five people with acute stroke. PROCEDURES: Participants received 3 h of an intensive hand and upper limb sensory and motor rehabilitation program, 5 days per week for 3 months (15-min mental imagery, 15-min action observation, 30-min mirror therapy, 1.5-h constraint-induced movement therapy, and 30-min bilateral arm training). Activities were chosen based on the task-oriented occupational therapy approach. OUTCOME MEASURES: An assessor blinded to intervention program measured sensory and motor functions using action research arm test, box and block test, Semmes-Weinstein monofilaments, and upper extremity section of Fugl-Meyer assessment. RESULTS: Assessment data points in intervention and follow-up phases compared to baseline were in higher levels, sloped upwardly, and increased significantly for all participants in all outcome measures. CONCLUSIONS: The present pilot study showed that a package of nowadays evidence-based rehabilitation methods including mental imagery, action observation, mirror therapy, modified constraint-induced movement therapy, bilateral arm training, and task-oriented occupational therapy approach is able to improve sensory and motor functions of the hand and upper limb in patients with acute stroke.

Unraveling Transformative Effects after tDCS and BCI Intervention in Chronic Post-Stroke Patient Rehabilitation-An Alternative Treatment Design Study.

Stroke is a debilitating clinical condition resulting from a brain infarction or hemorrhage that poses significant challenges for motor function restoration. Previous studies have shown the potential of applying transcranial direct current stimulation (tDCS) to improve neuroplasticity in patients with neurological diseases or disorders. By modulating the cortical excitability, tDCS can enhance the effects of conventional therapies. While upper-limb recovery has been extensively studied, research on lower limbs is still limited, despite their important role in locomotion, independence, and good quality of life. As the life and social costs due to neuromuscular disability are significant, the relatively low cost, safety, and portability of tDCS devices, combined with low-cost robotic systems, can optimize therapy and reduce rehabilitation costs, increasing access to cutting-edge technologies for neuromuscular rehabilitation. This study explores a novel approach by utilizing the following processes in sequence: tDCS, a motor imagery (MI)-based brain-computer interface (BCI) with virtual reality (VR), and a motorized pedal end-effector. These are applied to enhance the brain plasticity and accelerate the motor recovery of post-stroke patients. The results are particularly relevant for post-stroke patients with severe lower-limb impairments, as the system proposed here provides motor training in a real-time closed-loop design, promoting cortical excitability around the foot area (Cz) while the patient directly commands with his/her brain signals the motorized pedal. This strategy has the potential to significantly improve rehabilitation outcomes. The study design follows an alternating treatment design (ATD), which involves a double-blind approach to measure improvements in both physical function and brain activity in post-stroke patients. The results indicate positive trends in the motor function, coordination, and speed of the affected limb, as well as sensory improvements. The analysis of event-related desynchronization (ERD) from EEG signals reveals significant modulations in Mu, low beta, and high beta rhythms. Although this study does not provide conclusive evidence for the superiority of adjuvant mental practice training over conventional therapy alone, it highlights the need for larger-scale investigations.

[Effect and mechanism of Zuogui Pills on neural function recovery in ischemic stroke mice based on OPN/IGF-1/mTOR].

To explore the effect and mechanism of Zuogui Pills in promoting neural tissue recovery and functional recovery in mice with ischemic stroke. Male C57BL/6J mice were randomly divided into a sham group, a model group, and low-, medium, and high-dose Zuogui Pills groups(3.5, 7, and 14 g·kg~(-1)), with 15 mice in each group. The ischemic stroke model was established using photochemical embolization. Stiker remove and irregular ladder walking behavioral tests were conducted before modeling and on days 7, 14, 21, and 28 after medication. Triphenyl tetrazolium chloride(TTC) staining was performed on day 3 after modeling, and T2-weighted imaging(T2WI) and diffusion-weighted imaging(DWI) were performed on day 28 after medication to evaluate the extent of brain injury. Hematoxylin-eosin(HE) staining was performed to observe the histology of the cerebral cortex. Axonal marker proteins myelin basic protein(MBP), growth-associated protein 43(GAP43), mammalian target of rapamycin(mTOR), and its downstream phosphorylated s6 ribosomal protein(p-S6), as well as mechanism-related proteins osteopontin(OPN) and insulin-like growth factor 1(IGF-1), were detected using immunofluorescence and Western blot. Zuogui Pills had a certain restorative effect on the neural function impairment caused by ischemic stroke in mice. TTC staining showed white infarct foci in the sensory-motor cortex area, and T2WI imaging revealed cystic necrosis in the sensory-motor cortex area. The Zuogui Pills groups showed less brain tissue damage, fewer scars, and more capillaries. The number of neuronal axons in those groups was higher than that in the model group, and neuronal activity was stronger. The expression of GAP43, OPN, IGF-1, and mTOR proteins in the Zuogui Pills groups was higher than that in the model group. In summary, Zuogui Pills can promote the recovery of neural function and axonal growth in mice with ischemic stroke, and its mechanism may be related to the activation of the OPN/IGF-1/mTOR signaling pathway.

Relationship between resting-state functional connectivity and change in motor function after motor imagery intervention in patients with stroke: a scoping review.

BACKGROUND: In clinical practice, motor imagery has been proposed as a treatment modality for stroke owing to its feasibility in patients with severe motor impairment. Motor imagery-based interventions can be categorized as open- or closed-loop. Closed-loop intervention is based on voluntary motor imagery and induced peripheral sensory afferent (e.g., Brain Computer Interface (BCI)-based interventions). Meanwhile, open-loop interventions include methods without voluntary motor imagery or sensory afferent. Resting-state functional connectivity (rs-FC) is defined as a significant temporal correlated signal among functionally related brain regions without any stimulus. rs-FC is a powerful tool for exploring the baseline characteristics of brain connectivity. Previous studies reported changes in rs-FC after motor imagery interventions. Systematic reviews also reported the effects of motor imagery-based interventions at the behavioral level. This study aimed to review and describe the relationship between the improvement in motor function and changes in rs-FC after motor imagery in patients with stroke. REVIEW PROCESS: The literature review was based on Arksey and O'Malley's framework. PubMed, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science were searched up to September 30, 2023. The included studies covered the following topics: illusion without voluntary action, motor imagery, action imitation, and BCI-based interventions. The correlation between rs-FC and motor function before and after the intervention was analyzed. After screening by two independent researchers, 13 studies on BCI-based intervention, motor imagery intervention, and kinesthetic illusion induced by visual stimulation therapy were included. CONCLUSION: All studies relating to motor imagery in this review reported improvement in motor function post-intervention. Furthermore, all those studies demonstrated a significant relationship between the change in motor function and rs-FC (e.g., sensorimotor network and parietal cortex).

Scalp Acupuncture on the Immediate and Prolonged Motor Recovery in Spinal Cord Injury: a Case Report.

Spinal cord injury (SCI) is one of the main causes of lifelong motor impairment and is associated with important secondary complications. Thus, multifaceted treatments are needed for early functional recovery. Currently, in cases of SCI, surgery, stem cell treatment, medication, and physical therapy are used to repair and restore neuronal activity. Additionally, encouraging results have been reported on the use of acupuncture to modulate neuronal plasticity. Here, we present an SCI case involving a burst fracture at the L3 level, which was treated for 21 days using scalp acupuncture with residential physical therapy. Activation of the motor area was observed after the 1st day of treatment, with the patient completely regaining power and range of motion in the knees, Additionally, over 21 days, the patient exhibited markedly improved motor recovery and functional outcomes, which had not been observed over the previous six months. This report highlights the importance of complementing scalp acupuncture with intensive physical therapy for better motor recovery.

Combined effect of Brunnstrom's hand rehabilitation and functional electrical stimulation for improving hand function in patients with chronic stroke: A randomized controlled trial.

BACKGROUND: Motor recovery of the upper extremity is one of the most common challenging outcomes after stroke. OBJECTIVE: To find out the combined effects of Brunnstrom hand rehabilitation (BHR) and functional electrical stimulation for improving hand functions in patients with chronic stroke. STUDY DESIGN: Randomized controlled trial. METHOD: 25 participants, both male (n = 11) and female (n = 14), age group between 40 and 70 years were randomly divided into control group (n = 12) and experimental group (n = 13). The treatment protocol was continued 5 days per week, for 4 weeks. The experimental group received Brunnstrom hand training and functional electrical stimulation (FES) along with conventional physiotherapy. The control group received only conventional physiotherapy. Participants were evaluated at baseline and after 4 weeks of intervention. OUTCOME MEASURES: Fugl Meyer Assessment scale-upper extremity, Modified Ashworth scale, Handheld Dynamometer, and Jabsen Taylor Hand Function Test. Paired t-test was used to compare within-group variables and an independent t-test was used for between-group comparisons. P-value was set as 0.05 to minimize type-1 error. RESULTS: Statistically significant difference was obtained in favor of the experimental group undergoing FMA (p < .001), MAS (p = .004), JTHF (p = .018), and HHD (p < .001) in between-group analysis. However, both groups showed significant improvement [experimental group; FMA-UE (p < .001), MAS (p < .001); JTHF (p < .001), and HHD (p < .001), and control group; FMA-UE (p < .001), MAS (p < .001), JTHF (p < .001) and HHD (p < .001)] in within-group analysis at post-intervention. CONCLUSION: Brunnstrom hand rehabilitation and FES in combination were found to be more effective in improving hand function than conventional physiotherapy treatment. CLINICAL TRIAL REGISTRATION: URL: http://www.ctri.nic.in. No: CTRI/2019/06/019,905.

Effects of programmed flexor-extensor alternating electrical acupoint stimulation on upper limb motor functional reconstruction after stroke: study protocol for a double-blind, randomized controlled trial.

BACKGROUND: Stroke's prevalence and morbidity are increasing (Guano, et al. Neuro 89:53-61, 2017), and limb motor dysfunction is left in most patients (Gittler, et al. JAMA 319:820-821, 2018). Particularly, the rehabilitation of upper limbs is more difficult and time-consuming (Borges, et al. The Cochrane database of systematic reviews 10:CD011887, 2018). METHODS: A double-blind randomized controlled trial (RCT) will be conducted to investigate whether a new functional electrical stimulation (FES) combined with acupoint therapy is more effective in the rehabilitation of upper limb motor dysfunction after stroke. Patients who meet the inclusion criteria will be randomly divided into two groups: programmed flexor-extensor alternating electrical acupoint stimulation group (PES group) and conventional flexor-extensor alternating electrical acupoint stimulation group (CES group), which will be treated for 3 weeks. The primary outcome measures are electroencephalogram (EEG) and surface electromyogram (sEMG). The secondary outcome variables include MBI (modified Barthel index), China Stroke Scale (CSS), FMA-U (Fugl-Meyer assessment upper limb), MMT (manual muscle testing), and Brunnstrom. DISCUSSION: The results of this study are expected to verify the efficacy of PES therapy in the rehabilitation of upper limb motor function after stroke. This may promote the widespread use of the therapy in hospitals, communities, and homes for early and continuous treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT05333497. Registered on April 11, 2022.

Multiple sessions of therapeutic electrical stimulation using implantable thin-film wireless nerve stimulators improve functional recovery after sciatic nerve isograft repair.

INTRODUCTION/AIMS: Although therapeutic electrical stimulation (TES) of injured peripheral nerve promotes axon regeneration and functional recovery, clinical applications of this therapy are limited to the intraoperative timeframe. Implantable, thin-film wireless nerve stimulators offer a potential solution to this problem by enabling delivery of electrical stimuli to an injured nerve over a period of several days post-surgery. The aim of this study was to determine the optimal time course of stimulation for maximizing functional recovery in a rat sciatic nerve isograft repair model. METHODS: Adult male Lewis rats underwent thin-film wireless nerve stimulator implantation following sciatic nerve transection and 40 mm nerve isograft repair. Immediately after surgery, animals began a daily regimen of TES for up to 12 consecutive days. Functional recovery was assessed by compound muscle action potential (CMAP), evoked muscle force, wet muscle mass, and axon counting. RESULTS: Serial CMAP measurements increased in amplitude over the course of the study, yet no significant difference between cohorts for serial or terminal CMAPs was observed. Axon counts and wet muscle mass measurements were greatest in the 6-day stimulation group, which correlated with a significant increase in evoked muscle force for the 6-day stimulation group at the terminal time point. DISCUSSION: Six daily sessions of TES were found to be most effective for augmenting functional recovery compared to other time courses of stimulation. Future studies should incorporate additional subjects and track axonal sprouting or measure neurotrophin levels during the therapeutic window to further elucidate the mechanisms behind, and ideal amount of, TES.

Warm acupuncture therapy alleviates neuronal apoptosis after spinal cord injury via inhibition of the ERK signaling pathway.

PURPOSE: Warm acupuncture (WA) therapy has been applied to treat spinal cord injury (SCI), but the underlying mechanism is unclear. The current study attempted to explore the WA therapy on neuronal apoptosis of SCI and the relationship with the extracellular signal-regulated kinase (ERK) signaling pathway. METHODS: The rat SCI models were established by the impact method. SCI rat models were subjected to WA treatment at Dazhui (GV14) and Jiaji points (T10), Yaoyangguan (GV3), Zusanli (ST36), and Ciliao (BL32). The rat SCI models were established by the impact method. WA and U0126 treatments were performed on the SCI rats. Motor function and neuronal apoptosis were detected. The relative mRNA of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), the phosphorylation level of ERK 1/2 and levels of B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), and caspase-3 in spinal cord tissue were tested. RESULTS: After WA treatment, the Basso, Beattie & Bresnahan locomotor rating scale (BBB scale) of SCI rats in the WA treatment was significantly raised from 7 to 14 days after SCI. WA and U0126 treatment significantly diminished apoptotic cells and preserved the neurons in the injured spinal cord. WA and U0126 treatment alleviated the production of inflammatory cytokines in the spinal cord. The distinct increase of p-ERK 1/2 induced by SCI was reversed in WA and U0126 treatment groups. WA and U0126 treatment augmented the level of Bcl-2 and reversed the elevated cleaved caspase-3 protein level after SCI. CONCLUSION: Our study demonstrated that WA might be associated with the downregulation of the ERK signaling pathway. In summary, our findings indicated that WA promotes the recovery of SCI via the protection of nerve cells and the prevention of apoptosis. Meanwhile, the anti-apoptotic effect of WA might be associated with the downregulation of the ERK signaling pathway, which could be one of the mechanisms of WA in the treatment of SCI.

Enhancement of nerve regeneration with nimodipine treatment after sciatic nerve injury.

Peripheral nerve injuries (PNI/s) are common orthopedic conditions, characterized by motor and sensory deficits in the damaged region. There is growing evidence that the L-type calcium channel antagonist nimodipine has neuroprotective and neuroregenerative effects in animal models of neurological disorders. The efficacy of nimodipine on improving motor function and sensation following a sciatic nerve crush model was investigated in male Wistar rats as a model of PNI. At different time periods following damage, we evaluated motor function, sensory recovery, electrophysiology, histomorphometry, and gene expression. Moreover, we used histological and mass ratio analysis of the gastrocnemius muscle to assess atrophy. Our findings suggest that the nimodipine improves motor and sensory function more quickly in the damaged region 2, 4, and 6 weeks after 1 week of treatment. Nimodipine treatment also increased the number of myelinated fibers while decreasing their thickness, as shown by histomorphometry. Additionally, nimodipine treatment increases the mRNA levels of neurotrophic factors (BDNF and NGF), which are known to contribute to the regeneration of injured neurons. The impact of nimodipine in PNI recovery may be due to its stimulation of the CREB signaling pathway and suppression of pro-inflammatory factor production.

[Progress of researches on involvement of corticospinal tract in the effect of acupuncture on improvement of post-stroke motor dysfunction].

The corticospinal tract (CST), descending from the frontoparietal cortex and traveling down to terminate at the anterior horn of the spinal cord to mediate voluntary movements, is frequently injured from the infarcted or hemorrhagic cerebrovascular insults due to stroke. Under the circumstances, motor dysfunction seriously affects the patient's quality of life. Acupuncture therapy has a sequelae, especially in improving motor deficits. In the present paper, we reviewed the current development of researches on acupuncture treatment of poststroke motor dysfunction and its biological mechanisms from 1) delaying patients' development of neuronal degeneration and white matter fibrosis (Wallerian degeneration), 2) improving patients' upper limb motor function and daily life ability by promoting the repair of white matter tracts and CST on the affected side, 3) promoting the compensation of CST on the healthy side, 4) reconstructing the motor conduction pathway to strengthen the bilateral brain connection in ex-perimental animals, and 5) strengthening the sprouting of the contralateral CST to dominate the affected side again across the midline. In addition, acupuncture stimulation induced improvement of axonal rewiring for corticospinal innervation is also possibly related to its functions in accelerating the synthesis and release of neurotrophic factors, down-regulating Nogo-A/RhoA signaling and activating vascular epithelial growth factor/Dll4/Notch signaling pathways.

Effects of myofascial release with tennis ball on spasticity and motor functions of upper limb in patients with chronic stroke: A randomized controlled trial.

BACKGROUND: Impaired motor function and upper extremity spasticity are common concerns in patients after stroke. It is essential to plan therapeutic techniques to recover from the stroke. The objective of this study was to investigate the effects of myofascial release with the tennis ball on spasticity and motor functions of the upper extremity in patients with chronic stroke. METHODS: Twenty-two chronic stroke patients (male-16, female-6) were selected to conduct this study. Two groups were formed: the control group (n=11) which included conventional physiotherapy only and the experimental group (n=11) which included conventional physiotherapy along with tennis ball myofascial release - in both groups interventions were performed for 6 sessions (35 minutes/session) per week for a total of 4 weeks. The conventional physiotherapy program consisted of active and passive ROM exercises, positional stretch exercises, resistance strength training, postural control exercises, and exercises to improve lower limb functions. All patients were evaluated with a modified Ashworth scale for spasticity of upper limb muscles (biceps brachii, pronator teres, and the long finger flexors) and a Fugl-Meyer assessment scale for upper limb motor functions before and after 4 weeks. Nonparametric (Mann-Whitney U test and Wilcoxon signed-rank test) tests were used to analyze data statistically. This study has been registered on clinicaltrial.gov (ID: NCT05242679). RESULTS: A significant improvement (P < .05) was observed in the spasticity of all 3 muscles in both groups. For upper limb motor functions, significant improvement (P < .05) was observed in the experimental group only. When both groups were compared, greater improvement (P < .05) was observed in the experimental group in comparison to the control group for both spasticity of muscles and upper limb motor functions. CONCLUSION: Myofascial release performed with a tennis ball in conjunction with conventional physiotherapy has more beneficial effects on spasticity and motor functions of the upper extremity in patients with chronic stroke compared to conventional therapy alone.

Supplementation With Vitamin E, Zinc, Selenium, and Copper Re-Establishes T-Cell Function and Improves Motor Recovery in a Rat Model of Spinal Cord Injury.

Spinal cord injury (SCI) causes a dysfunction of sympathetic nervous system innervation that affects the immune system, leading to immunosuppression syndrome (ISS) and contributing to patient degeneration and increased risk of several infections. A possible therapeutic strategy that could avoid further patient deterioration is the supplementation with Vitamin E or trace elements, such as Zinc, Selenium, and Copper, which individually promotes T-cell differentiation and proliferative responses. For this reason, the aim of the present study was to evaluate whether Vitamin E, Zinc, Selenium, and Copper supplementation preserves the number of T-lymphocytes and improves their proliferative function after traumatic SCI. Sprague-Dawley female rats were subjected to moderate SCI and then randomly allocated into three groups: (1) SCI + supplements; (2) SCI + vehicle (olive oil and phosphate-buffered saline); and (3) sham-operated rats. In all rats, the intervention was initiated 15 min after SCI and then administered daily until the end of study. Locomotor recovery was assessed at 7 and 15 days after SCI. At 15 days after supplementation, the quantification of the number of T-cells and its proliferation function were examined. Our results showed that the SCI + supplements group presented a significant improvement in motor recovery at 7 and 15 days after SCI. In addition, this group showed a better T-cell number and proliferation rate than that observed in the group with SCI + vehicle. Our findings suggest that Vitamin E, Zinc, Selenium, and Copper supplementation could be part of a therapy for patients suffering from acute SCI, helping to preserve T-cell function, avoiding complications, and promoting a better motor recovery. All procedures were approved by the Animal Bioethics and Welfare Committee (Approval No. 201870; CSNBTBIBAJ 090812960).

Effectiveness of Repetitive Facilitative Exercise Combined with Electrical Stimulation Therapy to Improve Very Severe Paretic Upper Limbs in with Stroke Patients: A Randomized Controlled Trial.

Background: The difference in the effects of combined therapy with repetitive facilitative exercise (RFE) and neuromuscular electrical stimulation (NMES) on stroke upper limb paralysis was only reported by a pilot study; it has not been investigated in many patients. Objective: We investigated the effect of combined therapy with RFE and NMES on stroke patients with severe upper paresis. Methods: This study included 99 of the very severe paresis stroke patients with scores of zero or 1a in the Finger-Function test of the Stroke Impairment Assessment Set (SIAS). We randomly divided the patients into four groups, namely, NMES, RFE, RFE under NMES, and conventional training (CT) groups. A total of 20 min of group-specific training in addition to 40 min of conventional exercise per day, seven times a week for 4 weeks after admission, was performed. The upper extremity items of the Fugl-Meyer Assessment (FMA) were evaluated before and after the training period. Results: The total score gains of the FMA, FMA wrist item, and FMA finger item were significantly larger in the RFE under NMES group than those in the CT group (p < 0.05). Conclusion: The combination of voluntary movement and electrical stimulation may promote the activation of paralyzed muscles and improve distal function for very severe paralyzed upper limbs.

Effectiveness of Tai Chi Yunshou motor imagery training for hemiplegic upper extremity motor function in poststroke patients: study protocol for a randomized clinical trial.

BACKGROUND: Evidence concerning the effect of Tai Chi Yunshou motor imagery training (TCY-MIT) on upper extremity motor function (UE-MF) recovery in poststroke patients is lacking, and few studies have examined the neural mechanisms of MIT. The study was designed to assess the effectiveness of TCY-MIT and its possible neural mechanisms. METHODS/DESIGN: The study is an assessor-blinded, parallel, superiority, randomized clinical trial. A total of 78 eligible participants will be randomly assigned to 2 groups in a 1:1 ratio. Participants in the control group will receive (conventional rehabilitation therapies) CRTs for 40 min per day, 6 days per week, for 3 weeks. Participants in the intervention group will receive CRTs combined with TCY-MIT (30 min per day, 6 days per week, for 3 weeks). The primary outcome measure is the Fugl-Meyer Assessment of Upper Extremity. Secondary outcome measures are the Box and Block Test, muscle strength test, modified Barthel index, and Pearson correlation coefficients. All outcomes will be assessed at baseline, after completion of the intervention (1, 2, and 3 weeks), and at the end of follow-up (2 months). The outcome assessor will be blinded to the group allocation of the participants. DISCUSSION: We expect this assessor-blinded, parallel, superiority, randomized clinical trial to explore the effectiveness of TCY-MIT combined with CRTs compared with CRTs alone for UE-MF in poststroke patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ID: ChiCTR2100048868 . Registered on 19 July 2021.

Time to Functional Recovery After Laser Tonsillotomy Performed Under Local Anesthesia vs Conventional Tonsillectomy With General Anesthesia Among Adults: A Randomized Clinical Trial.

Importance: Carbon dioxide laser tonsillotomy performed under local anesthesia may be an effective and less invasive alternative than dissection tonsillectomy for treatment of tonsil-related afflictions. Objective: To compare functional recovery and symptom relief among adults undergoing tonsillectomy or tonsillotomy. Design, Setting, and Participants: This randomized clinical trial was conducted at 5 secondary and tertiary hospitals in the Netherlands from January 2018 to December 2019. Participants were 199 adult patients with an indication for surgical tonsil removal randomly assigned to either the tonsillectomy or tonsillotomy group. Interventions: For tonsillotomy, the crypts of the palatine tonsil were evaporated using a carbon dioxide laser under local anesthesia, whereas tonsillectomy consisted of total tonsil removal performed under general anesthesia. Main Outcomes and Measures: The primary outcome was time to functional recovery measured within 2 weeks after surgery assessed for a modified intention-to-treat population. Secondary outcomes were time to return to work after surgery, resolution of primary symptoms, severity of remaining symptoms, surgical complications, postoperative pain and analgesics use, and overall patient satisfaction assessed for the intention-to-treat population. Results: Of 199 patients (139 [70%] female; mean [SD] age, 29 [9] years), 98 were randomly assigned to tonsillotomy and 101 were randomly assigned to tonsillectomy. Recovery within 2 weeks after surgery was significantly shorter after tonsillotomy than after tonsillectomy (hazard ratio for recovery after tonsillectomy vs tonsillotomy, 0.3; 95% CI, 0.2-0.5). Two weeks after surgery, 72 (77%) patients in the tonsillotomy group were fully recovered compared with 26 (57%) patients in the tonsillectomy group. Time until return to work within 2 weeks was also shorter after tonsillotomy (median [IQR], 4.5 [3.0-7.0] days vs 12.0 [9.0-14.0] days; hazard ratio for return after tonsillectomy vs tonsillotomy, 0.3; 95% CI, 0.2-0.4.). Postoperative hemorrhage occurred in 2 patients (2%) in the tonsillotomy group and 8 patients (12%) in the tonsillectomy group. At 6 months after surgery, fewer patients in the tonsillectomy group (25; 35%) than in the tonsillotomy group (54; 57%) experienced persistent symptoms (difference of 22%; 95% CI, 7%-37%). Most patients with persistent symptoms in both the tonsillotomy (32 of 54; 59%) and tonsillectomy (16 of 25; 64%) groups reported mild symptoms 6 months after surgery. Conclusions and Relevance: This randomized clinical trial found that compared with tonsillectomy performed under general anesthesia, laser tonsillotomy performed under local anesthesia had a significantly shorter and less painful recovery period. A higher percentage of patients had persistent symptoms after tonsillotomy, although the intensity of these symptoms was lower than before surgery. These results suggest that laser tonsillotomy performed under local anesthesia may be a feasible alternative to conventional tonsillectomy in this population. Trial Registration: Netherlands Trial Register Identifier: NL6866 (NTR7044).

Short-Duration, Pulsatile, Electrical Stimulation Therapy Accelerates Axon Regeneration and Recovery following Tibial Nerve Injury and Repair in Rats.

BACKGROUND: Repair of nerve injuries can fail to achieve adequate functional recovery. Electrical stimulation applied at the time of nerve repair can accelerate axon regeneration, which may improve the likelihood of recovery. However, widespread use of electrical stimulation may be limited by treatment protocols that increase operative time and complexity. This study evaluated whether a short-duration electrical stimulation protocol (10 minutes) was efficacious to enhance regeneration following nerve repair using rat models. METHODS: Lewis and Thy1-green fluorescent protein rats were randomized to three groups: 0 minutes of electrical stimulation (no electrical stimulation; control), 10 minutes of electrical stimulation, and 60 minutes of electrical stimulation. All groups underwent tibial nerve transection and repair. In the intervention groups, electrical stimulation was delivered after nerve repair. Outcomes were assessed using immunohistochemistry, histology, and serial walking track analysis. RESULTS: Two weeks after nerve repair, Thy1-green fluorescent protein rats demonstrated increased green fluorescent protein-positive axon outgrowth from the repair site with electrical stimulation compared to no electrical stimulation. Serial measurement of walking tracks after nerve repair revealed recovery was achieved more rapidly in both electrical stimulation groups as compared to no electrical stimulation. Histologic analysis of nerve distal to the repair at 8 weeks revealed robust axon regeneration in all groups. CONCLUSIONS: As little as 10 minutes of intraoperative electrical stimulation therapy increased early axon regeneration and facilitated functional recovery following nerve transection with repair. Also, as early axon outgrowth increased following electrical stimulation with nerve repair, these findings suggest electrical stimulation facilitated recovery because of earlier axon growth across the suture-repaired site into the distal nerve to reach end-organ targets. CLINICAL RELEVANCE STATEMENT: Brief (10-minute) electrical stimulation therapy can provide similar benefits to the 60-minute protocol in an acute sciatic nerve transection/repair rat model and merit further studies, as they represent a translational advantage.

Effectiveness of a Novel Contralaterally Controlled Neuromuscular Electrical Stimulation for Restoring Lower Limb Motor Performance and Activities of Daily Living in Stroke Survivors: A Randomized Controlled Trial.

Background: Contralaterally controlled neuromuscular electrical stimulation (CCNMES) is a novel electrical stimulation treatment for stroke; however, reports on the efficacy of CCNMES on lower extremity function after stroke are scarce. Objective: To compare the effects of CCNMES versus NMES on lower extremity function and activities of daily living (ADL) in subacute stroke patients. Methods: Forty-four patients with a history of subacute stroke were randomly assigned to a CCNMES group and a NMES group (n = 22 per group). Twenty-one patients in each group completed the study per protocol, with one subject lost in follow-up in each group. The CCNMES group received CCNMES to the tibialis anterior (TA) and the peroneus longus and brevis muscles to induce ankle dorsiflexion motion, whereas the NMES group received NMES. The stimulus current was a biphasic waveform with a pulse duration of 200 µs and a frequency of 60 Hz. Patients in both groups underwent five 15 min sessions of electrical stimulation per week for three weeks. Indicators of motor function and ADL were measured pre- and posttreatment, including the Fugl-Meyer assessment of the lower extremity (FMA-LE) and modified Barthel index (MBI). Surface electromyography (sEMG) assessments included average electromyography (aEMG), integrated electromyography (iEMG), and root mean square (RMS) of the paretic TA muscle. Results: Values for the FMA-LE, MBI, aEMG, iEMG, and RMS of the affected TA muscle were significantly increased in both groups after treatment (p < 0.01). Patients in the CCNMES group showed significant improvements in all the measurements compared with the NMES group after treatment. Within-group differences in all post- and pretreatment indicators were significantly greater in the CCNMES group than in the NMES group (p < 0.05). Conclusion: CCNMES improved motor function and ADL ability to a greater extent than the conventional NMES in subacute stroke patients.

Types of Vascular Response to Direct Intraoperative Electrical Stimulation of the Sciatic Nerve after Autoneuroplasty and Their Effect on Limb Function Recovery.

We studied different types of the vascular response to direct intraoperative low-frequency electrical stimulation of the sciatic nerve after autoneuroplasty of its tibial portion and analyzed their effects on the limb function recovery. Rats (n=20) underwent 40-min intraoperative electrical stimulation, and hemodynamics in the leg was recorded by photoplethysmography. Functional recovery of the tibial nerve was assessed using a walking path analysis within 12 weeks after surgery. Three types of the vascular response to electrical stimulation were identified: the absence of pronounced hemodynamic changes during the electrostimulation session, hyperkinetic type of hemodynamics, and venous outflow disturbances. In rats demonstrating vascular responses of types I and II during the postoperative period, the functional index of the tibial nerve partially recovered within 12 weeks; in type III, no recovery was observed. It was concluded that the type of hemodynamics during intraoperative electrical stimulation of the damaged nerve subjected to autoneuroplasty affects further restoration of the motor function of the limb.

Combining Optogenetic Stimulation and Motor Training Improves Functional Recovery and Perilesional Cortical Activity.

Background. An ischemic stroke is followed by the remapping of motor representation and extensive changes in cortical excitability involving both hemispheres. Although stimulation of the ipsilesional motor cortex, especially when paired with motor training, facilitates plasticity and functional restoration, the remapping of motor representation of the single and combined treatments is largely unexplored. Objective. We investigated if spatio-temporal features of motor-related cortical activity and the new motor representations are related to the rehabilitative treatment or if they can be specifically associated to functional recovery. Methods. We designed a novel rehabilitative treatment that combines neuro-plasticizing intervention with motor training. In detail, optogenetic stimulation of peri-infarct excitatory neurons expressing Channelrhodopsin 2 was associated with daily motor training on a robotic device. The effectiveness of the combined therapy was compared with spontaneous recovery and with the single treatments (ie optogenetic stimulation or motor training). Results. We found that the extension and localization of the new motor representations are specific to the treatment, where most treatments promote segregation of the motor representation to the peri-infarct region. Interestingly, only the combined therapy promotes both the recovery of forelimb functionality and the rescue of spatio-temporal features of motor-related activity. Functional recovery results from a new excitatory/inhibitory balance between hemispheres as revealed by the augmented motor response flanked by the increased expression of parvalbumin positive neurons in the peri-infarct area. Conclusions. Our findings highlight that functional recovery and restoration of motor-related neuronal activity are not necessarily coupled during post-stroke recovery. Indeed the reestablishment of cortical activation features of calcium transient is distinctive of the most effective therapeutic approach, the combined therapy.