Physical exercise to promote regeneration after peripheral nerve injury in animal models: A systematic review.

Peripheral nerve injuries are common injuries that often have a drastic effect on patient's activities of daily living and physical function. While techniques for the surgical repair of these injuries have improved over time, rehabilitation methods following these repairs have been non-standardized and under researched. Electronic searches were conducted in Ovid/Medline and SCOPUS to identify articles that discuss rehabilitation and exercise following peripheral nerve injury in animal models and its effects on peripheral nerve regeneration and recovery of function. Thirty-eight articles met inclusion criteria; all were prospective studies in animal models. This systematic review suggests that exercise is a useful tool in returning autonomy to the individual and has beneficial effects in the recovery from peripheral nerve injury. It is beneficial to use rehabilitation exercises following the repair of peripheral nerve injuries to promote regeneration, and timing of that exercise may be just as important as the exercise prescribed. However, further studies with standardized models and outcome measures need to be conducted before translation to clinical trials.

Efeitos de um protocolo de exercícios de força, flexibilidade e equilíbrio nas lesões de nervos periféricos: um estudo de caso / Effects of a strength, flexibility, and balance exercise protocol on peripheral nerve injuries: a case study

Introdução: As lesões de nervos periféricos são mais frequentes em membros superiores (MMSS), que são importantes para as atividades de vida diárias, equilíbrio e reflexos de proteção. Alterações no sistema de controle postural podem impactar na funcionalidade desses indivíduos. Portanto, é necessário alternativas para melhorar as alterações secundárias à lesão. Objetivo: Avaliar os efeitos de um protocolo de exercícios de força, flexibilidade e equilíbrio em paciente com lesão de nervos periféricos. Métodos: Estudo de caso de abordagem quantitativa realizado na Clínica Escola de Fisioterapia da Unochapecó, entre abril e julho de 2021, totalizando 30 intervenções de 60 minutos cada. A amostra foi constituída por um paciente do sexo masculino, 46 anos com diagnóstico de lesão de nervos periféricos no MMSS direito, decorrente de um acidente motociclístico. Foi realizada avaliação inicial, aplicação do protocolo, após a realização das escalas e testes: BESTest, MiniBESTest, Romberg-Barré, Dinamometria manual isométrica, Teste de Sentar e Alcançar e Mini-Exame do Estado Mental. O protocolo continha exercícios de força, flexibilidade e equilíbrio. Os dados foram analisados através de estatística descritiva comparativa, antes e após o protocolo (média e porcentagem). Resultados: Houve melhora na força muscular, flexibilidade toracolombar (aumento de 13 cm "61,90%") e testes de equilíbrio (15,81% BESTest, 21,42% MiniBESTest e 67,16% Romberg-Barré). Conclusão: O protocolo de exercícios refletiu positivamente na melhora da flexibilidade, força muscular e equilíbrio do paciente, tornando-se uma alternativa viável para melhorar as alterações secundárias a lesão. (AU)

The effects of sensory re-education on hand function recovery after peripheral nerve repair: A systematic review.

BACKGROUND: Peripheral nerve injury can result in both sensory and motor deficits, and these impairments can last for a long period after nerve repair. OBJECTIVE: To systematically review the effects of sensory re-education (SR) on facilitating hand function recovery after peripheral nerve repair. METHODS: This systematic review was limited to articles published from 1970 to 20 December 2020. Electronic searching was performed in CINAHL, Embase, PubMed, Web of Science, and Medline databases to include trials investigating the effects of SR training on hand function recovery after peripheral nerve repair and included only those studies with controlled comparisons. RESULTS: Sixteen articles were included in final data synthesis. We found that only four studies could be rated as having good quality and noted obvious methodological limitations in the remaining studies. The current evidence showed that early SR with mirror visual feedback and the combinational use of classic SR and topical temporary anesthetic seemed to have long- and short-term effects, respectively on improving the sensibility and reducing the disabilities of the hand. The evidence to support the effects of conventional classical SR on improving hand functions was not strong. CONCLUSIONS: Further well-designed trials are needed to evaluate the effects of different SR techniques on hand function after nerve repair over short- and long-term periods.

Electromagnetic field and TGF-ß enhance the compensatory plasticity after sensory nerve injury in cockroach Periplaneta americana.

Recovery of function after sensory nerves injury involves compensatory plasticity, which can be observed in invertebrates. The aim of the study was the evaluation of compensatory plasticity in the cockroach (Periplaneta americana) nervous system after the sensory nerve injury and assessment of the effect of electromagnetic field exposure (EMF, 50 Hz, 7 mT) and TGF-ß on this process. The bioelectrical activities of nerves (pre-and post-synaptic parts of the sensory path) were recorded under wind stimulation of the cerci before and after right cercus ablation and in insects exposed to EMF and treated with TGF-ß. Ablation of the right cercus caused an increase of activity of the left presynaptic part of the sensory path. Exposure to EMF and TGF-ß induced an increase of activity in both parts of the sensory path. This suggests strengthening effects of EMF and TGF-ß on the insect ability to recognize stimuli after one cercus ablation. Data from locomotor tests proved electrophysiological results. The takeover of the function of one cercus by the second one proves the existence of compensatory plasticity in the cockroach escape system, which makes it a good model for studying compensatory plasticity. We recommend further research on EMF as a useful factor in neurorehabilitation.

The tactile experience paired with vagus nerve stimulation determines the degree of sensory recovery after chronic nerve damage.

Loss of sensory function is a common consequence of neurological injury. Recent clinical and preclinical evidence indicates vagus nerve stimulation (VNS) paired with tactile rehabilitation, consisting of delivery of a variety of mechanical stimuli to the hyposensitive skin surface, yields substantial and long-lasting recovery of somatosensory function after median and ulnar nerve transection and repair. Here, we tested the hypothesis that a specific component of the tactile rehabilitation paired with VNS is necessary for recovery of somatosensory function. In a second experiment in a separate cohort, we investigated whether VNS paired with tactile rehabilitation could improve skilled forelimb motor function. Elements of the study design, including planned sample size, assessments, and statistical comparisons, were preregistered prior to beginning data collection (https://osf.io/3tm8u/). Animals received a peripheral nerve injury (PNI) causing chronic sensory loss. Eight weeks after injury, animals were given a VNS implant followed by six weeks of tactile rehabilitation sessions consisting of repeated application of one of two distinct mechanical stimuli, a filament or a paintbrush, to the previously denervated forepaw. VNS paired with either filament indentation or brushing of the paw significantly improved recovery of forelimb withdrawal thresholds after PNI compared to tactile rehabilitation without VNS. The effect size was twice as large when VNS was paired with brushing compared to VNS paired with point indentation. An independent replication in a second cohort confirmed that VNS paired with brush restored forelimb withdrawal thresholds to normal. These rats displayed significant improvements in performance on a skilled forelimb task compared to rats that did not receive VNS. These findings support the utility of pairing VNS with tactile rehabilitation to improve recovery of somatosensory and motor function after neurological injury. Additionally, this study demonstrates that the sensory characteristics of the rehabilitation paired with VNS determine the degree of recovery.

Analyzing the functional effects of dynamic and static splints after radial nerve injury.

The radial nerve is a commonly injured upper extremity peripheral nerve. The inability to extend the wrist results in a loss of hand function and dexterity that affects patients' ability to perform their activities of daily living. There is no strong evidence to support a particular splint design for improving dexterity. This cohort study compared whether a static or dynamic splint can improve hand dexterity when assessed with the 9-hole peg test (9-HPT) after radial nerve injury. Thirty-four subjects with radial nerve palsy participated in the study. The test was repeated three times for each subject, first without the splint, and then while wearing the control static wrist splint, and finally while wearing the dynamic splint. The 9-HPT was used as the outcome measure. The 9-HPT times were 36.4±4.8seconds without a wrist splint and improved when using the static and the dynamic splints to 33.5±4.5seconds (P<0.01) and 25.7±3.5seconds (P<0.01) respectively. The use of a dynamic splint after radial nerve palsy can provide the patient with greater manual dexterity when compared to using no splint or a static splint.

Cold intolerance and neuropathic pain after peripheral nerve injury in upper extremity.

Cold intolerance and pain can be a substantial problem in patients with peripheral nerve injury. We aimed at investigating the relationships among sensory recovery, cold intolerance, and neuropathic pain in patients affected by upper limb peripheral nerve injury (Sunderland type V) treated with microsurgical repair, followed by early sensory re-education. In a cross-sectional clinical study, 100 patients (male/female 81/19; age 40.5 ± 14.8 years and follow-up 17 ± 5 months, mean ± SD), with microsurgical nerve repair and reconstruction in the upper extremity and subsequent early sensory re-education, were evaluated, using Cold Intolerance Symptoms Severity questionnaire-Italian version (CISS-it, cut-off pathology >30/100 points), CISS questionnaire-12 item version (CISS-12, 0-46 points-grouping: healthy that means no cold intolerance [0-14], mild [15-24], moderate [25-34], severe [35-42], very severe [43-46] cold intolerance), probability of neuropathic pain (DouleurNeuropathique-4; [DN4] 4/10), deep and superficial sensibility, tactile threshold (monofilaments), and two-point discrimination (cutoff S2; Medical Research Council scale for sensory function; [MRC-scale]). A high CISS score is associated with possible neuropathic pain (DN4 ≥ 4). Both a low CISS-it score (ie, < 30) and DN4 < 4 is associated with good sensory recovery (MRC ≥ 2). In conclusion patients affected by upper limb peripheral nerve injuries with higher CISS scores more often suffer from cold intolerance and neuropathic pain, and the better their sensory recovery is, the less likely they are to suffer from cold intolerance and neuropathic pain.

Calotropis procera (root) escalates functions rehabilitation and attenuates oxidative stress in a mouse model of peripheral nerve injury.

Peripheral nerve injuries result in sensorimotor functional loss, leading to permanent disability and physical dependency with immense cost and reduced quality of life. These injuries are among those complicated medical situations which still are waiting for their first-line treatment. This study was designed to investigate the role of Calotropis procera (crude roots) in accelerating functional retrieval following mechanically induced sciatic nerve injury in healthy albino male mice. Following acclimatization, mice were grouped equally as "Control" fed on normal chow and "Root" fed on C. procera root (100mg/kg/day) mixed chow. A mechanical crush was induced in right sciatic nerve of animals. Behavioral analyses (grip strength, SFI, pinprick and hot plate tests) were conducted for assessing sensorimotor function reclamation and blood was collected for oxidative stress assessment. Significantly earlier retrieval of sensorimotor activities (p<0.05), reduced total oxidant status, increased total antioxidant capacity with prominently enhanced arylesterase and paraoxonase activities (p<0.001) in treatment group suggested positive impact of C. procera roots on quickening functional recovery and combating oxidative stress following nerve injury. Thus C. procera root can be considered as potential candidate drug for further investigation to seek bioactive compound/s that may actually responsible for ameliorative functional recovery following nerve injury.

Enhancing function after radial nerve injury with a high-profile orthosis and a bio-occupational orthotic framework.

STUDY DESIGN: Case report. INTRODUCTION: Radial nerve injury can cause severe functional impairment due to paralysis of wrist and digit extensors. Various orthotic designs have been described, including static, dynamic, and tenodesis. All provide wrist stabilization or extension assistance. Some, but not all, also provide extension assistance to the wrist, thumb, and fingers. PURPOSE AND METHODS: This article tells the story of Max, a 27-year-old male university student, who sustained a radial nerve injury after a left humeral shaft fracture. He was treated at a Brazilian tertiary hospital, where the choice of thermoplastics and dynamic components resulted in limited options for orthotic fabrication. Max was provided with custom-molded static wrist orthosis and a bulky, older style, high-profile dynamic forearm-based wrist-finger-thumb assistive-extension orthosis. RESULTS AND DISCUSSION: Grip strength and functional status improved, and Max was completely satisfied because with the dynamic orthosis, he could play the guitar again, which was his favorite activity. CONCLUSION: Max's story illustrates that a convenient functionally oriented orthotic intervention can be performed even in resource-limited environments by following the client-centered bio-occupational orthotic framework proposed by McKee and Rivard. This framework addresses the client's biological needs (addressing paralyzed muscles and maintaining length of soft tissues) and occupational/functional needs.

Motoneuron activity is required for enhancements in functional recovery after peripheral nerve injury in exercised female mice.

Inhibitory luminopsins (iLMO2) integrate opto- and chemo-genetic approaches and allow for cell-type specific inhibition of neuronal activity. When exposed to a Renilla luciferase substrate, Coelenterazine (CTZ), iLMO2 generates bioluminescence-mediated activation of its amino-terminal halorhodopsin, resulting in neuronal inhibition. Moderate daily exercise in the form of interval treadmill-training (IT) applied following a peripheral nerve injury results in enhanced motor axon regeneration and muscle fiber reinnervation in female mice. We hypothesized that iLMO2 mediated inhibition of motoneuron activity during IT would block this enhancement. Unilateral intramuscular injections of Cre-dependent AAV2/9-EF1a-DIO-iLMO2 (∼8.5 x 1013 vg/ml) were made into the gastrocnemius and tibialis anterior muscles of young female ChAT-IRES-Cre mice, thereby limiting iLMO2 expression specifically to their motoneurons. Four to six weeks were allowed for retrograde viral transduction after which a unilateral sciatic nerve transection (Tx) and repair was performed. Animals were randomized into four groups: IT only, IT + CTZ, CTZ only, and untreated (UT). Three weeks post Tx-repair, the maximal amplitude direct muscle responses (M-max) in both muscles in the IT only group were significantly greater than in UT mice, consistent with the enhancing effects of this exercise regimen. Inhibiting motoneuron activity during exercise by a single injection of CTZ, administered 30 minutes prior to exercise, completely blocked the enhancing effect of exercise. Similar treatments with CTZ in mice without iLMO2 had no effect on regeneration. Neuronal activity is required for successful enhancement of motor axon regeneration by exercise.

Management of large peripheral nerve defects with autografting.

INTRODUCTION: A segmental nerve defect from trauma results in significant loss of function of the extremity, and rarely occurs in isolation. Autografting of the nerve defect is the current gold standard. METHODS: A review of the recent literature regarding peripheral nerve defects after trauma treated with autograft. RESULTS: Identification of the zone of nerve injury is difficult and appropriate resection is critical for good outcomes. Meaningful recovery is more likely with application of excellent technique. Many of the factors affecting outcomes are not modifiable. CONCLUSION: Nerve grafting for segmental nerve injuries continues to be an essential and appropriate treatment.

Effects of Repeated 20-Hz Electrical Stimulation on Functional Recovery Following Peripheral Nerve Injury.

One hour of 20-Hz continuous electrical stimulation (ES) applied at the time of injury promotes the regeneration of axons in cut peripheral nerves. A more robust enhancement of peripheral axon regeneration is achieved by 2 weeks of daily treadmill exercise. We investigated whether repeated applications of brief ES (mES) would be more effective in promoting regeneration than a single application. Sciatic nerves of C57B6 mice were cut and repaired by end-to-end anastomosis. At that time and every third day for 2 weeks, the repaired nerve was stimulated for 1 hour at 20 Hz. In controls, injured mice were either untreated or treated with ES only once. Direct muscle responses recorded from reinnervated muscles in awake animals were observed earlier both in mice treated with ES and mES than untreated controls. Their amplitudes increased progressively over the post transection study period, but the rate of this progression was increased significantly only in animals treated once with ES. Monosynaptic H reflexes recovered to pretransection levels in both untreated and singly treated mice but in the animals treated repeatedly, they were maintained at more than twice that of the same reflexes recorded prior to injury. In anatomical analyses, both excitatory and inhibitory synaptic contacts with the cell bodies of injured motoneurons, including those expressing the vesicular glutamate transporter 1 (VGLUT1), were sustained in mice treated repeatedly but not in singly treated or untreated mice. Repeated ES does not enhance the rate of restoration of functional muscle reinnervation and results in the retention of exaggerated reflexes.

A Touch-Observation and Task-Based Mirror Therapy Protocol to Improve Sensorimotor Control and Functional Capability of Hands for Patients With Peripheral Nerve Injury.

IMPORTANCE: To develop a practical program in the early phase after nerve repair for more rapid return of function. OBJECTIVE: To investigate the effects of touch-observation and task-based mirror therapy on the sensorimotor outcomes of patients with nerve repair. DESIGN: An assessor-blinded study with a randomized controlled design. SETTING: University hospital. PARTICIPANTS: We recruited 12 patients with median or ulnar nerve repair between the level of midpalm and elbow referred by the plastic surgeons. INTERVENTION: The patients were randomized into touch-observation and task-based mirror therapy or control groups, and both groups received training for 12 wk. OUTCOMES AND MEASURES: The Semmes-Weinstein monofilament (SWM) test, two-point discrimination test, Purdue Pegboard Test (PPT), Minnesota Manual Dexterity Test (MMDT), and pinch-holding-up activity test were assessed at pretreatment, immediately after treatment, and 12 wk after the last treatment. RESULTS: The experimental group showed greater improvements in the results of the pinch-holding-up activity test and the PPT Unilateral Pin Insertion, Bilateral Pin Insertion, and Assembly subtests. However, change on the SWM test revealed no significant difference between the two groups. CONCLUSIONS AND RELEVANCE: Touch-observation and task-based mirror therapy is an effective but low-cost treatment protocol to optimize sensorimotor control and functional capability of the upper limb in patients with peripheral nerve injury.

Electrophysiologic recovery of the abductor pollicis brevis after contralateral C7 nerve transfer in 95 patients with global brachial plexus avulsion.

In this study, we investigated the electrophysiologic recovery of the abductor pollicis brevis (APB) muscle after contralateral seventh cervical (cC7) nerve transfer for the treatment of global brachial plexus avulsion (GBPA). We retrospectively analyzed the electromyography records of 95 patients with GBPA, comprising 81 men and 14 women, focusing on the motor unit potential (MUP) recovery of the APB. All patients underwent cC7-median nerve (MN) transfer. The cC7 nerve was transferred to the MN alone in 58 patients (One-Nerve Group), whereas 37 patients underwent cC7 transfer to the MN and another nerve (Two-Nerve Group). Fifty-three patients (MUP Group) exhibited MUP recovery of the APB, whereas 42 patients did not (No-MUP Group). The MUP Group comprised 32 patients from the One-Nerve Group and 21 patients from the Two-Nerve Group. The mean age of the MUP Group was significantly lower than that of the No-MUP Group. In summary, electrophysiologic recovery of the APB was common in patients with GBPA after cC7-MN transfer, indicating that it may be possible to restore the function of the intrinsic muscles of the hand after GBPA. The rehabilitation strategy for patients with GBPA, which overlooks the restoration of intrinsic hand muscle function, may require amendment.

Luxatio erecta humeri with humeral greater tuberosity fracture and axillary nerve injury.

Luxatio erecta humeri is the rarest type of glenohumeral dislocation, which has been reported to be associated with humeral fracture, rotator cuff tear and neurovascular injury. To our knowledge, a single-sided acute inferior glenohumeral dislocation associated with humeral greater tuberosity fracture and axillary nerve injury has not yet been reported. Here, we reported a traumatic first-time inferior shoulder dislocation from a construction worker who got hyperflexion of the left shoulder when fell and grasped the railing causing. The patient underwent traction counter-traction closed reduction followed by proper immobilization, and rehabilitation therapy. At thirteen months follow-up, the patient had returned to the workload that required high stress on shoulder joint with an excellent outcome.

Electromyographic Biofeedback in Motor Function Recovery After Peripheral Nerve Injury: An Integrative Review of the Literature.

Electromyographic biofeedback (EMG-BF) has been applied to treat different types of peripheral nerve injuries (PNI). However, despite the clinical practice widespread use its evidence is controversial. With the objective of summarize the available evidence on the electromyographic biofeedback effectiveness and efficacy to help motor function recovery after PNI an integrative review was performed. A secondary objective was to identify the conceptual framework and strategies of EMG-BF intervention, and the quality of technical description of EMG-BF procedures. To conduct this integrative review a systematic search of the literature was performed between October 2013 and July 2018, in PUBMED, ISI and COCHRANE databases for EMG-BF original studies in PNI patients of any etiology, in English, Portuguese, Spanish or French, published after 1990. Exclusion criteria were poor description of EMG-BF treatment, associated treatment that could impair EMG-BF effect, inclusion of non-PNI individuals and case studies design. The PEDro scale was used to evaluate study quality of randomized clinical trials (RCTs) included. This resulted in 71 potential articles enrolled to full reading, although only nine matched the inclusion criteria. PNI included facial paralysis, acute sciatic inflammation and carpal tunnel syndrome. The average quality score of the included RCTs was five, corresponding to low methodological quality. Due to the small number of included articles, low quality studies and heterogeneity of interventions, outcomes and population we concluded that there is limited evidence of EMG-BF effectiveness and efficacy for motor function recovery in PNI patients.

Management of an iatrogenic injury to the tibial nerve in a 24-year-old hurdle runner.

According to previously published papers, neurovascular injuries seem to be the most unfortunate complications after surgical procedures. In this report, we present our therapeutic approach to iatrogenic injury of the posterior tibial nerve that occurred during ankle arthroscopy in a 24-year-old patient. The outcome of the therapy was a full sensory return and partial motor return (S4 and M3 according to the Medical Research Council Grading System for Nerve Recovery). Our patient was able to resume her typical training. In comparison with available reports, our therapeutic approach enabled earlier functional recovery after nerve injury. While sensory return is beneficial, motor improvement is also important. However, we are conscious of the poor functional outcomes reported by other researchers.