Xu-Yun Hua

Long-term ongoing cortical remodeling after contralateral C-7 nerve transfer

OBJECT Contralateral C-7 nerve transfer was developed for the treatment of patients with brachial plexus avulsion injury (BPAI). In the surgical procedure the affected recipient nerve is connected to the ipsilateral motor cortex, and the dramatic peripheral alteration may trigger extensive cortical reorganization. However, little is known about the long-term results after such specific nerve transfers. The purpose of this study was to investigate the long-term cortical adaptive plasticity after BPAI and contralateral C-7 nerve transfer. METHODS In this study, 9 healthy male volunteers and 5 male patients who suffered from right-sided BPAI and had undergone contralateral C-7-transfer more than 5 years earlier were included. Functional MRI studies were used for the investigation of long-term cerebral plasticity. RESULTS The neuroimaging results suggested that the ongoing cortical remodeling process after contralateral C-7 nerve transfer could last for a long period; at least for 5 years. The motor control of the reinnervated limb may finally transfer from the ipsilateral to the contralateral hemisphere exclusively, instead of the bilateral neural network activation. CONCLUSIONS The authors believe that the cortical remodeling may last for a long period after peripheral rearrangement and that the successful cortical transfer is the foundation of the independent motor recovery.

Contralateral Peripheral Neurotization for Hemiplegic Upper Extremity After Central Neurologic Injury

BACKGROUND Central neurological injury (CNI) is a major contributor to physical disability that affects both adults and children all over the world. The main sequelae of chronic stage CNI are spasticity, paresis of specific muscles, and poor selective motor control. Here, we apply the concept of contralateral peripheral neurotization in spasticity releasing and motor function restoration of the affected upper extremity. OBJECTIVE A clinical investigation was performed to verify the clinical efficacy of contralateral C7 neurotization for rescuing the affected upper extremity after CNI. METHODS In the present study, 6 adult hemiplegia patients received the nerve transfer surgery of contralateral C7 to C7 of the affected side. Another 6 patients with matched pathological and demographic status were assigned to the control group that received rehabilitation only. During the 2-year follow-up, muscle strength of bilateral upper extremities was assessed. The Modified Ashworth Scale and Fugl-Meyer Assessment Scale were used for evaluating spasticity and functional use of the affected upper extremity, respectively. RESULTS Both flexor spasticity release and motor functional improvements were observed in the affected upper extremity in all 6 patients who had surgery. The muscle strength of the extensor muscles and the motor control of the affected upper extremity improved significantly. There was no permanent loss of sensorimotor function of the unaffected upper extremity. CONCLUSION This contralateral C7 neurotization approach may open a door to promote functional recovery of upper extremity paralysis after CNI.

Trial of Contralateral Seventh Cervical Nerve Transfer for Spastic Arm Paralysis

BACKGROUND Spastic limb paralysis due to injury to a cerebral hemisphere can cause long‐term disability. We investigated the effect of grafting the contralateral C7 nerve from the nonparalyzed side to the paralyzed side in patients with spastic arm paralysis due to chronic cerebral injury. METHODS We randomly assigned 36 patients who had had unilateral arm paralysis for more than 5 years to undergo C7 nerve transfer plus rehabilitation (18 patients) or to undergo rehabilitation alone (18 patients). The primary outcome was the change from baseline to month 12 in the total score on the Fugl–Meyer upper‐extremity scale (scores range from 0 to 66, with higher scores indicating better function). RESULTS The mean increase in Fugl–Meyer score in the paralyzed arm was 17.7 in the surgery group and 2.6 in the control group (difference, 15.1; 95% confidence interval, 12.2 to 17.9; P<0.001). With regard to improvements in spasticity as measured on the Modified Ashworth Scale (an assessment of five joints, each scored from 0 to 5, with higher scores indicating more spasticity), the smallest between‐group difference was in the thumb, with 6, 9, and 3 patients in the surgery group having a 2‐unit improvement, a 1‐unit improvement, or no change, respectively, as compared with 1, 6, and 7 patients in the control group (P=0.02). Transcranial magnetic stimulation and functional imaging showed connectivity between the ipsilateral hemisphere and the paralyzed arm. There were no significant differences from baseline to month 12 in power, tactile threshold, or two‐point discrimination in the hand on the side of the donor graft. CONCLUSIONS In this single‐center trial involving patients who had had unilateral arm paralysis due to chronic cerebral injury for more than 5 years, transfer of the C7 nerve from the nonparalyzed side to the side of the arm that was paralyzed was associated with a greater improvement in function and reduction of spasticity than rehabilitation alone over a period of 12 months. Physiological connectivity developed between the ipsilateral cerebral hemisphere and the paralyzed hand. (Funded by the National Natural Science Foundation of China and others; Chinese Clinical Trial Registry number, 13004466.)

Different cerebral plasticity of intrinsic and extrinsic hand muscles after peripheral neurotization in a patient with brachial plexus injury: A TMS and fMRI study

Contralateral C7 (CC7) neurotization has been an important approach for brachial plexus injury (BPI). Patients can achieve relatively good grasping function driven by the proximal extrinsic hand muscle (flexor digitorum, FD) after CC7 neurotization, whereas the thumb opposition function driven by the distal intrinsic muscle (abductor pollicis brevis, APB) is poor. The present study aimed to investigate the brain reorganization patterns of the recovery processes of intrinsic and extrinsic hand functions after repairing the median nerve by CC7 neurotization. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) were used to evaluate the cerebral plasticity in one BPI patient after CC7 neurotization. After the CC7 neurotization, the patient showed improvements in the paralyzed hand. Combination of TMS and fMRI investigations demonstrated different cortical reshaping patterns of APB and FD. It was also found that the activated cortical areas of FD were located in bilateral motor cortices, but the area of APB was only located in ipsilateral motor cortex. The cerebral plasticity procedure appeared to be different in the gross and fine motor function recovery processes. It provided a new perspective into the cerebral plasticity induced by CC7 neurotization.

Interhemispheric functional reorganization after cross nerve transfer: via cortical or subcortical connectivity?

It has been demonstrated that there could be long range interhemispheric reorganization between bilateral hemispheres after peripheral cross nerve transfer. Our previous studies found a striking dynamic process of interhemispheric functional reorganization in adult rats with cross seventh cervical nerve transfer. But it remains a question whether the extensive interhemispheric functional reorganization after cross nerve transfer depends on connectivities at the cortical or subcortical level. In the present study, 18 rats with cross C7 transfer were concurrently treated with corpus callosotomy while the other 18 were not. Intracortical microstimulation was performed in the primary motor cortex (M1) at intervals of 5, 7, and 10 months postoperatively. The neural electrophysiology study showed that the representation of the injured forepaw appeared in the ipsilateral cortex at 5 months after the cross nerve transfer combined with corpus callosotomy, and it shared great overlapping zones with the representation of the health forepaw. And then, at 7-10 months, the cortical representation of the paralyzed forepaw was still located in the ipsilateral motor cortex, although significantly contracted. In contrast, rats with mere cross nerve transfer still presented interhemispheric reorganization. The results indicated that corpus callosotomy in the early stage after cross C7 transfer may had interrupted the interhemispheric functional reorganization. Combined the present study with our previous research findings, we explored the possible pathway and mechanisms of the interhemispheric functional reorganization. Thus we came to the conclusion that interhemispheric connectivity at the cortical level was essential in establishing the new contralateral control of the paralyzed limb at the initial stage after cross nerve transfer.

Diagnosing neurogenic thoracic outlet syndrome with the triple stimulation technique.

OBJECTIVE We assessed the diagnostic value of triple stimulation technique (TST) in eight patients with neurogenic thoracic outlet syndrome (TOS) by revealing the conduction block of the proximal lower trunk of the brachial plexus and locating the compression site. METHODS Eight patients fulfilling the conventional criteria of the lower-trunk neurogenic TOS were enrolled in our study. TST along with the central motor-conduction time was evaluated. The parameters including the TST amplitude ratio and the TST area ratio were compared between patients and controls. RESULTS The amplitude ratio was significantly lower in the patient group than in the control group (patients: 0.518 ± 0.113; control: 0.954 ± 0.020, P<0.01), so was the area ratio (patients: 0.453 ± 0.194; control group: 0.955 ± 0.192, P<0.01). No significant difference of central motor-conduction time (CMCT) was seen between the patient group and the control group (patients: 6.62 ± 0.36 ms; control: 6.54 ± 0.36 ms; P=0.528). Surgical procedures proved the compression of the lower trunk in all patients. CONCLUSION Our results indicated that there was conduction block besides axon loss in neurogenic TOS patients, and the conduction block was located between the nerve root emerging site and the supraclavicular stimulation site. SIGNIFICANCE We first applied TST in diagnosing neurogenic TOS, and we showed that the patients TST ratio was significantly lower than normal. Combined with clinical manifestations, TOS can be more precisely diagnosed.

Reversion of transcallosal interhemispheric neuronal inhibition on motor cortex after contralateral C7 neurotization.

Department of Hand Surgery, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China Department of Radiology, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China PET Center, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China State Key Laboratory of Medical Neuroscience, Fudan University, 138, Yi Xue Road, Shanghai 200032, China

Supplementary motor area deactivation impacts the recovery of hand function from severe peripheral nerve injury

Although some patients have successful peripheral nerve regeneration, a poor recovery of hand function often occurs after peripheral nerve injury. It is believed that the capability of brain plasticity is crucial for the recovery of hand function. The supplementary motor area may play a key role in brain remodeling after peripheral nerve injury. In this study, we explored the activation mode of the supplementary motor area during a motor imagery task. We investigated the plasticity of the central nervous system after brachial plexus injury, using the motor imagery task. Results from functional magnetic resonance imaging showed that after brachial plexus injury, the motor imagery task for the affected limbs of the patients triggered no obvious activation of bilateral supplementary motor areas. This result indicates that it is difficult to excite the supplementary motor areas of brachial plexus injury patients during a motor imagery task, thereby impacting brain remodeling. Deactivation of the supplementary motor area is likely to be a serious problem for brachial plexus injury patients in terms of preparing, initiating and executing certain movements, which may be partly responsible for the unsatisfactory clinical recovery of hand function.

Brain functional network abnormality extends beyond the sensorimotor network in brachial plexus injury patients

Brachial plexus injury (BPI) is a type of severe peripheral nerve trauma that leads to central remodeling in the brain, as revealed by functional MRI analysis. However, previously reported remodeling is mostly restricted to sensorimotor areas of the brain. Whether this disturbance in the sensorimotor network leads to larger-scale functional remodeling remains unknown. We sought to explore the higher-level brain functional abnormality pattern of BPI patients from a large-scale network function connectivity dimension in 15 right-handed BPI patients. Resting-state functional MRI data were collected and analyzed using independent component analysis methods. Five components of interest were recognized and compared between patients and healthy subjects. Patients showed significantly altered brain local functional activities in the bilateral fronto-parietal network (FPN), sensorimotor network (SMN), and executive-control network (ECN) compared with healthy subjects. Moreover, functional connectivity between SMN and ECN were significantly less in patients compared with healthy subjects, and connectivity strength between ECN and SMN was negatively correlated with patients’ residual function of the affected limb. Functional connectivity between SMN and right FPN were also significantly less than in controls, although connectivity between ECN and default mode network (DMN) was greater than in controls. These data suggested that brain functional disturbance in BPI patients extends beyond the sensorimotor network and cascades serial remodeling in the brain, which significantly correlates with residual hand function of the paralyzed limb. Furthermore, functional remodeling in these higher-level functional networks may lead to cognitive alterations in complex tasks.

Local and Extensive Neuroplasticity in Carpal Tunnel Syndrome: A Resting-State fMRI Study:

Carpal tunnel syndrome (CTS) is a most common peripheral nerve entrapment neuropathy characterized by sensorimotor deficits in median nerve innervated digits. Block-design task-related functional magnetic resonance imaging (fMRI) studies have been used to investigate CTS-related neuroplasticity in the primary somatosensory cortices. However, considering the persistence of digital paresthesia syndrome caused by median nerve entrapment, spontaneous neuronal activity might provide a better understanding of CTS-related neuroplasticity, which remains unexplored. The present study aimed to investigate both local and extensive spontaneous neuronal activities with resting-state fMRI. A total of 28 bilateral CTS patients and 24 normal controls were recruited, and metrics, including amplitude of low-frequency fluctuation (ALFF) and voxel-wise functional connectivity (FC), were used to explore synaptic activity at different spatial scales. Correlations with clinical measures were further investigated by linear regression. Decreased amplitudes of low-frequency fluctuation were observed in the bilateral primary sensory cortex (SI) and secondary sensory cortex (SII) in CTS patients (AlphaSim corrected P < .05). This was found to be negatively related to the sensory thresholds of corresponding median nerve innervated fingers. In the voxel-wise FC analysis, with predefined seed regions of interest in the bilateral SI and primary motor cortex, we observed decreased interhemispheric and increased intrahemispheric FC. Additionally, both interhemispheric and intrahemispheric FC were found to be significantly correlated with the mean ALFF.