Peripheral Cross-neurotization Inducing Unaffected Hemisphere Reorganization To Enhance The Motor Control Of The Spastic Hemiplegic Hand After Central Neurologic Injury

Background:Central neurologic injury which was resulted from different etiologies may lead to dysfunction and disability in patients. Typical treatments for the central neurologic injury are insufficient and far from satisfied, esepecially for the upper extremity. Many researches explored the recovery mechanisms after contral neurologic injury. It was realized that the ipsilateral motor pathway originating from the unaffected hemisphere may be accessed or recruited to compensate for damage to the crossed pathways which is usually limited by the quantity of spared projection fibers in the spinal cord. In the present study, we demonstrated that the ipsilateral neural projection could be enhanced significantly and the unaffected hemisphere could control both the unaffected and paralyzed upper extremities after a peripheral neurotization surgery named cross-neck C7-C7neurotization.Methods:In the animal experiment we established a rat model of middle cerebral artery occlusion and the contralateral C7nerve transfer. Both forelimb use asymmetry test and reaching task were used for the behavior assessment. Micro PET was used to explore the brain plasticity correspond to the contralateral C7nerve transfer. In the clinical investigation, we performed the operation on6young patients (median age11years old. range4-13) with at least2years follow-up. Modified Ashworth Scale (MAS) and Quality of Upper Extremity Skills Test (QUEST) were used for evaluations of spasticity and functional use of the paralyzed upper extremity. Both neurophysiological (transcranial magnetic stimulation-motor evoked potential, TMS-MEP) and neuroimaging (fMRI. PET) studies were used for detecting the cerebral plasticity after peripheral neurotization. Results:In the animal experiment we found the behavior scores decreased significantly after the brian ischmic injury in both the control group (left cerebral ischemia) and experimental group (left cerebral ischemia+contralateral C7transfer) at2weeks after operation. The scores improved at1month after the injury, howvere, it is far from satisfied. The rat in the control group would not regain any improvements in the behavior test until10months after the injury while the experimental group started to recover at5months after injury. In the Micro PET test, we found that the neural activation in the ipsilateral cortex of the experiemental group was much higher than that in control group (P<0.05. FDR correction). Longitudinal analyzed showed that elevation of the cerebral glucose metabolism (CGM) in ipsilateral motor cortex correlated with the scores of reaching task, suggesting a significant positive correlation with the recovery of the affected forpaw. At the follow-up of the clinical investigation, we observed significant motor recovery and release of flexion deformity of the paralyzed upper extremities in all6patients. The scores of MAS and QUEST improved significantly. Transcranial magnetic stimulation of the unaffected ipsilateral motor cortex could effectively induce motor action potentials in both unaffected and paralyzed upper extremities. fMRI imaging showed significant activation of ipsilateral primary motor cortex (MI) while activating extension of the affected wrists. PET longitudinal imaging showed elevation of the cerebral glucose metabolism (CGM) in ipsilateral primary motor cortex (MI) and supplementary motor area (SMA) correlated with the QUEST scores, suggesting a significant positive correlation with the recovery of the affected arm in all the patients.Conclusion:The results demonstrate improvement of the strength and motor function of the whole limb in response to the ipsilateral motor control over the paralyzed upper extremity. Cross-neck C7-C7neurotization is a novel surgical strategy for treating a paralyzed upper extremity caused by a central neurologic injury.