Contralateral cervical seventh nerve transfer for spastic arm paralysis via a modified prespinal route: a cadaveric study.

BACKGROUND: We proposed contralateral cervical seventh nerve transfer for spastic arm paralysis after central neurological injury in the New England Journal of Medicine (NEJM) in 2018. In this surgery, we applied a new surgical route for nerve transfer, the Huashan prespinal route. The objective of this study was to elaborate our new surgical technique, clarify its relationship to the vertebral artery, and provide anatomical data on this novel method. METHODS: The effectiveness and safety of the Huashan prespinal route in contralateral C7 nerve transfer were evaluated anatomically. Nine cadavers (4 males, 5 females) were available for this study. Among these, anatomical parameters of the vertebral artery were obtained from 6 cadavers, and the anastomosis of the bilateral cervical seventh nerve was observed on 3 cadavers undergoing contralateral C7 nerve transfer via the Huashan prespinal route. RESULTS: Tension-free anastomosis of the bilateral cervical seventh nerve was achieved through the Huashan prespinal route. The tilt angle of the vertebral artery to the sagittal plane (with thyroid cartilage as the origin) was 25.5 ± 4.5°, at 22.5 ± 1.6° and 28.7 ± 4.3° on the left and right side, respectively. The safe drilling angle to penetrate through the longus colli muscles for the creation of a longus colli muscle tunnel to avoid injury to the vertebral artery in our surgical technique was above 33.2°. CONCLUSIONS: The cadaveric study confirms that the presented technique allowed simple, effective, and safe contralateral C7 nerve transfer. This technique can be used in the treatment of hemiplegia and brachial plexus injury. There is a safe scope of drilling angle for creating the longus colli muscle tunnel required for this surgical route. The anatomical parameters obtained in this study will be helpful for the performance of this operation.

Actomyosin-II protects axons from degeneration induced by mild mechanical stress.

Whether, to what extent, and how the axons in the central nervous system (CNS) can withstand sudden mechanical impacts remain unclear. By using a microfluidic device to apply controlled transverse mechanical stress to axons, we determined the stress levels that most axons can withstand and explored their instant responses at nanoscale resolution. We found mild stress triggers a highly reversible, rapid axon beading response, driven by actomyosin-II-dependent dynamic diameter modulations. This mechanism contributes to hindering the long-range spread of stress-induced Ca2+ elevations into non-stressed neuronal regions. Through pharmacological and molecular manipulations in vitro, we found that actomyosin-II inactivation diminishes the reversible beading process, fostering progressive Ca2+ spreading and thereby increasing acute axonal degeneration in stressed axons. Conversely, upregulating actomyosin-II activity prevents the progression of initial injury, protecting stressed axons from acute degeneration both in vitro and in vivo. Our study unveils the periodic actomyosin-II in axon shafts cortex as a novel protective mechanism, shielding neurons from detrimental effects caused by mechanical stress.

Outcomes and prognostic factors for nerve grafting following high radial nerve injury.

In this study, we examined the prognostic factors affecting outcomes following nerve grafting in high radial nerve injuries. Thirty-three patients with radial nerve injuries at a level distal to the first branch to the triceps and proximal to the posterior interosseous nerve were retrospectively studied. After a follow-up of at least 1 year, 24 patients (73%) obtained M3+ wrist extension, 16 (48%) obtained M3+ finger extension and only ten (30%) obtained M3+ thumb extension. Univariate, multivariate and receiver operating characteristic analyses showed that a delay in the repair of less than 6 months, a defect length of less than 5 cm or when grafted with three or more donor nerve cables achieved better recovery. Number of cables used was related to muscle strength recovery but not time to reinnervation. Nerve grafting for high radial nerve injury achieved relatively good wrist extension but poor thumb extension and is affected by certain prognostic factors. Level of evidence: IV.

Restoring After Central Nervous System Injuries: Neural Mechanisms and Translational Applications of Motor Recovery.

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are leading causes of long-term disability. It is estimated that more than half of the survivors of severe unilateral injury are unable to use the denervated limb. Previous studies have focused on neuroprotective interventions in the affected hemisphere to limit brain lesions and neurorepair measures to promote recovery. However, the ability to increase plasticity in the injured brain is restricted and difficult to improve. Therefore, over several decades, researchers have been prompted to enhance the compensation by the unaffected hemisphere. Animal experiments have revealed that regrowth of ipsilateral descending fibers from the unaffected hemisphere to denervated motor neurons plays a significant role in the restoration of motor function. In addition, several clinical treatments have been designed to restore ipsilateral motor control, including brain stimulation, nerve transfer surgery, and brain-computer interface systems. Here, we comprehensively review the neural mechanisms as well as translational applications of ipsilateral motor control upon rehabilitation after CNS injuries.

Crossing nerve transfer drives sensory input-dependent plasticity for motor recovery after brain injury.

Restoring limb movements after central nervous system injury remains a substantial challenge. Recent studies proved that crossing nerve transfer surgery could rebuild physiological connectivity between the contralesional cortex and the paralyzed arm to compensate for the lost function after brain injury. However, the neural mechanism by which this surgery mediates motor recovery remains still unclear. Here, using a clinical mouse model, we showed that this surgery can restore skilled forelimb function in adult mice with unilateral cortical lesion by inducing cortical remapping and promoting corticospinal tract sprouting. After reestablishing the ipsilateral descending pathway, resecting of the artificially rebuilt peripheral nerve did not affect motor improvements. Furthermore, retaining the sensory afferent, but not the motor efferent, of the transferred nerve was sufficient for inducing brain remapping and facilitating motor restoration. Thus, our results demonstrate that surgically rebuilt sensory input triggers neural plasticity for accelerating motor recovery, which provides an approach for treating central nervous system injuries.

Aberrant central plasticity underlying synchronous sensory phenomena in brachial plexus injuries after contralateral cervical seventh nerve transfer.

BACKGROUNDS: Contralateral cervical seventh (C7) nerve transfer aids motor and sensory recovery in total brachial plexus avulsion injuries (TBPI), but synchronous sensation often persists postoperatively. The mechanism underlying synchronous sensory phenomena remain largely unknown. OBJECTIVE: To investigate the role of central plasticity in sensory recovery after contralateral C7 nerve transfer. METHODS: Sixteen right TBPI patients who received contralateral C7 nerve transfer for more than 2 years were included. Sensory evaluations included Semmes-Weinstein monofilament assessment (SWM), synchronous sensation test, and sensory evoked action potential (SNAP) test. Smaller value in the SWM assessment and larger amplitude of SNAP indicates better tactile sensory. Functional magnetic resonance imaging was performed while stimulations delivered to each hand separately in block-design trials for central plasticity analysis. RESULTS: The SWM value of the injured right hand was increased compared with the healthy left side (difference: 1.76, 95% confidence interval: 1.37-2.15, p < .001), and all 16 patients developed synchronous sensation. In functional magnetic resonance imaging analysis, sensory representative areas of the injured right hand were located in its ipsilateral S1, and 23.4% of this area overlapped with the representative area of the left hand. The ratio of overlap for each patient was significantly correlated with SWM value and SNAP amplitude of the right hand. CONCLUSION: The tactile sensory functioning of the injured hand was dominated by its ipsilateral SI in long-term observation, and its representative area largely overlapped with the representative area of the intact hand, which possibly reflected a key mechanism of synchronous sensation in patients with TBPI after contralateral C7 transfer.

A Mouse Model of Direct Anastomosis via the Prespinal Route for Crossing Nerve Transfer Surgery.

Crossing nerve transfer surgery has been a powerful approach for repairing injured upper extremities in patients with brachial plexus avulsion injuries. Recently, this surgery was creatively applied in the clinical treatment of brain injury and achieved substantial rehabilitation of the paralyzed arm. This functional recovery after the surgery suggests that peripheral sensorimotor intervention induces profound neuroplasticity to compensate for the loss of function after brain damage; however, the underlying neural mechanism is poorly understood. Therefore, an emergent clinical animal model is required. Here, we simulated clinical surgery to establish a protocol of direct anastomosis of bilateral brachial plexus nerves via the prespinal route in mice. Neuroanatomical, electrophysiological, and behavioral experiments helped identify that the transferred nerves of these mice successfully reinnervated the impaired forelimb and contributed to accelerating motor recovery after brain injury. Therefore, the mouse model revealed the neural mechanisms underlying rehabilitation upon crossing nerve transfer after central and peripheral nervous system injuries.

A novel mouse model of contralateral C7 transfer via the pretracheal route: A feasibility study.

BACKGROUND: Contralateral seventh cervical nerve transfer (contralateral C7 transfer) is a novel treatment for patients with spastic paralysis, including stroke and traumatic brain injury. However, little is known on changes in plasticity that occur in the intact hemisphere after C7 transfer. An appropriate surgical model is required. NEW METHOD: We described in detail the anatomy of the C7 in a mouse model. We designed a pretracheal route by excising the contralateral C6 lamina ventralis, and the largest nerve defect necessary for direct neurorrhaphy was compared with defect lengths in a prespinal route. To test feasibility, we performed in-vivo surgery and assessed nerve regeneration by immunofluorescence, histology, electrophysiology, and behavioral examinations. RESULTS: Two types of branching were found in the anterior and posterior divisions of C7, both of which were significantly larger than the sural nerve. The length of the nerve defect was drastically reduced after contralateral C6 lamina ventralis excision. Direct tension-free neurorrhaphy was achieved in 66.7% of mice. The expression of neurofilament in the distal segment of the regenerated C7 increased. Histological examination revealed remyelination. Behavioral tests and electrophysiology tests showed functional recovery in a traumatic brain injury mouse. COMPARISON WITH EXISTING METHODS: This is the first direct tension-free neurorrhaphy mouse model of contralateral C7 transfer which shortened the time of nerve regeneration; previous models have used nerve grafting. CONCLUSIONS: This paper describes a simple, reproducible, and effective mouse model of contralateral C7 transfer for studying brain plasticity and exploring potential new therapies after unilateral cerebral injury.

Contralateral C7 to C7 nerve root transfer in reconstruction for treatment of total brachial plexus palsy: anatomical basis and preliminary clinical results.

OBJECTIVEContralateral C7 (CC7) nerve root has been used as a donor nerve for targeted neurotization in the treatment of total brachial plexus palsy (TBPP). The authors aimed to study the contribution of C7 to the innervation of specific upper-limb muscles and to explore the utility of C7 nerve root as a recipient nerve in the management of TBPP.METHODSThis was a 2-part investigation. 1) Anatomical study: the C7 nerve root was dissected and its individual branches were traced to the muscles in 5 embalmed adult cadavers bilaterally. 2) Clinical series: 6 patients with TBPP underwent CC7 nerve transfer to the middle trunk of the injured side. Outcomes were evaluated with the modified Medical Research Council scale and electromyography studies.RESULTSIn the anatomical study there were consistent and predominantly C7-derived nerve fibers in the lateral pectoral, thoracodorsal, and radial nerves. There was a minor contribution from C7 to the long thoracic nerve. The average distance from the C7 nerve root to the lateral pectoral nerve entry point of the pectoralis major was the shortest, at 10.3 ± 1.4 cm. In the clinical series the patients had been followed for a mean time of 30.8 ± 5.3 months postoperatively. At the latest follow-up, 5 of 6 patients regained M3 or higher power for shoulder adduction and elbow extension. Two patients regained M3 wrist extension. All regained some wrist and finger extension, but muscle strength was poor. Compound muscle action potentials were recorded from the pectoralis major at a mean follow-up of 6.7 ± 0.8 months; from the latissimus dorsi at 9.3 ± 1.4 months; from the triceps at 11.5 ± 1.4 months; from the wrist extensors at 17.2 ± 1.5 months; from the flexor carpi radialis at 17.0 ± 1.1 months; and from the digital extensors at 22.8 ± 2.0 months. The average sensory recovery of the index finger was S2. Transient paresthesia in the hand on the donor side, which resolved within 6 months postoperatively, was reported by all patients.CONCLUSIONSThe C7 nerve root contributes consistently to the lateral pectoral nerve, the thoracodorsal nerve, and long head of the triceps branch of the radial nerve. CC7 to C7 nerve transfer is a reconstructive option in the overall management plan for TBPP. It was safe and effective in restoring shoulder adduction and elbow extension in this patient series. However, recoveries of wrist and finger extensions are poor.