Reimplantation of ventral rootlets into the cervical spinal cord after their avulsion: an anterior surgical approach
Abstract
Root avulsions from the cervical spinal cord due to traction injuries are beyond repair up to the present day. An anterior surgical approach has been developed in cats for reimplantation of the ventral rootlets into the site of avulsion. The consecutive surgical steps towards exposure of the ventral surface of the cervical cord are given in detail. The morphological relations during the operative procedure are explained in the text and by illustrations. In this study the surgery related mortality rate was 16% and the overall mortality rate amounted to 21%. Loss of blood, initially a major problem, was coped with by increasing technical experience and the infusion of plasma expanding fluid. In 2 animals with survival times of 209 and 293 days respectively, many ventral horn motoneurons were found HRP-positive after retrograde HRP transport through the site of reimplantation. The findings provide evidence that the axonal continuity between reimplanted ventral roots and their motoneurons may be restored.
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Cited by (33)
Brachial Plexus Avulsion: A Model for Axonal Regeneration Study
2015, Neural RegenerationRoot avulsion of the brachial plexus is a devastating injury that results in massive motoneuron death and paralysis of the corresponding muscle groups. Various approaches such as pharmaceutical applications and microsurgical interventions have been extensively studied to restore the loss of injured motoneurons and recover function. However, the treatment for brachial plexus injury is still a challenging problem. The challenge that lies in brachial plexus injury treatment is that motoneuron death in the lesioned segments is relatively high and little is known about how inhibitory signals or lack of appropriate guidance molecules influences regeneration. This chapter summarizes the anatomical structure of the brachial plexus, the experimental models of brachial plexus avulsion, neuronal and glial responses to avulsion injury, and cellular and molecular profiles in the avulsed spinal cord at various ages and in various species. This chapter also summarizes a number of potential strategies for the treatment of brachial plexus avulsion, including microsurgical interventions using peripheral nerve graft or ventral root reimplantation; the use of small molecules, trophic factors, or small interfering RNA to promote motoneuron survival and regeneration; the application of inhibitors of the degeneration pathway; cell-based therapies; and, last, combined therapies for brachial plexus avulsion. We believe that a combination of multiple treatments may be necessary to acquire the most beneficial effects in treating the devastating injury characterized by motoneuron loss.
Spinal repair of ventral root avulsions after brachial plexus injuries: Towards new surgical strategies?
2006, NeurochirurgieLes avulsions radiculaires du plexus brachial sont des lésions dramatiques dont le pronostic fonctionnel reste très mauvais. Regardées comme des lésions du système nerveux central, elles sont toujours considérées comme irréparables. Pourtant de nombreuses expériences chez l’animal ont montré que si la continuité est rétablie entre la moelle cervicale et un muscle dénervé ou l’extrémité distale de son nerf, les axones des motoneurones spinaux peuvent repousser à travers un greffon de nerf périphérique avec récupération fonctionnelle. Une première expérience a été réalisée chez l’homme par une équipe anglaise avec de modestes résultats. Malgré les controverses issues de ces premiers travaux, nous avons voulu démontrer que la repousse axonale après réimplantation intra-spinale d’une racine avulsée est une réalité chez l’homme, qu’elle s’accompagne d’une récupération fonctionnelle, et qu’elle devrait pouvoir constituer la base de nouvelles stratégies chirurgicales.
Nous avons dans un premier temps étudié l’anatomie du compartiment intra-dural et développé l’abord postérieur du plexus brachial pour une implantation dans le cordon ventro-latéral de la moelle. Le caractère non permissif à la repousse axonale de la substance blanche du système nerveux central nous a ensuite conduit à démontrer l’intérêt d’implanter directement le greffon dans le sillon ventro-latéral pour atteindre la corne antérieure de la substance grise. Dans ce but, nous avons développé au laboratoire l’abord chirurgical direct de la corne antérieure, et appliqué cette technique chez des patients qui présentaient des avulsions radiculaires multiples et étagées.
La réimplantation médullaire n’a entraîné aucune complication neurologique. Aucun des patients ne présente de co-contraction musculaire. Une ré-innervation partielle des muscles triceps et biceps, et a été obtenue selon le type de lésion et de greffe. La supplémentation neurotrophique constitue une voie de recherche parallèle qui pourrait permettre d’améliorer les résultats fonctionnels de la réparation spinale des avulsions radiculaires.
Avulsion of nerve roots associated with the brachial plexus results in dramatic lesions with a prognosis which remains poor to this day. These lesions are considered as involving the central nervous system and therefore not amenable to surgical repair. However, the results of many experiments in animals have shown that if continuity can be re-established between the cervical cord and a denervated muscle or the distal end of its nerve, spinal motor neurons can regrow into a peripheral nerve graft, ultimately leading to the restoration of functional contraction. A preliminary experiment was attempted in humans but the outcomes were modest. In light of all the controversy raised by these preliminary results, we sought to demonstrate that axons can indeed regrow after intra-spinal re-implantation of an avulsed nerve root, that such re-growth can lead to the recovery of function, and that the phenomenon should be focused upon for the development of new surgical modalities to correct this serious condition.
We first studied the anatomy of the intradural compartment and developed a posterior approach to the brachial plexus for implantation in the ventrolateral aspect of the spinal cord. The fact that the white matter of the central nervous system is not propitious for axon re-growth led us to investigate the advantages of directly implanting the graft in the ventrolateral sulcus of the spinal cord in order that it might reach the anterior horn of the gray matter. In order to do this, we developed in the laboratory a direct surgical approach to the anterior horn, an approach which we subsequently used in patients with avulsion of multiple nerve roots at different levels.
Intraspinal re-implantation did not induce any neurological complications and co-contraction of different muscles was not observed in any of the patients. Partial re-innervation was obtained of the triceps, biceps and deltoid muscles, the exact pattern depending on the type of lesion and the type of graft. Treatment with neurotrophic factors represents a parallel line of research which might well help improve outcomes in spinal surgery to repair nerve root avulsion.
Polyneuropathies
2006, Consultations in Feline Internal MedicineEffects of root replantation and neurotrophic factor treatment on long-term motoneuron survival and axonal regeneration after C7 spinal root avulsion
2005, Experimental NeurologyIn order to determine the effect of nerve root replantation on motoneuron survival and regeneration, we have avulsed and replanted C7 ventral rootlets in adult rabbits under various conditions. Intraspinal alterations and exact positions of ventrolateral replantations were studied in each animal, and the effects of BDNF and/or CNTF administration during replantation investigated in different experimental groups. Six months after lesion, about 70% of motoneurons were lost on the lesioned sides in the C7 segment, without significant differences between groups. Retrograde fluorescent tracing and histological analysis documented that many axons had regrown through the original ventral exit zones or had exited the spinal cord at the lateral replantation site. However, many laterally exiting axons had not grown out directly from the ventral horn through the lateral white matter but had elongated vertically before leaving the spinal cord. The mean axonal diameter was significantly higher in regenerated axons that had exited through the original ventral exit zones in comparison with axons which had grown out laterally. Application of BDNF and/or CNTF did not show any effects on the pathways of regeneration into the replanted root. The results indicate that motoneuron survival cannot be significantly improved by a single dose of neurotrophic factors applied to a ventrolateral replantation site. However, a significant number of myelinating axons are found in replanted roots, and regeneration may be more efficient when outgrowth through the original ventral exit zone is supported.
Le transfert controlatéral du rameau ventral C8 droit (neurotisation croisée de C8) a été réalisé chez 6 chats adultes chez lesquels la partie caudale du plexus brachial (C8 et T1) avait été sectionnée du côté gauche afin de mimer la clinique observée lors d’avulsion du plexus brachial caudal.
Une évaluation clinique, électrophysiologique et histologique a été réalisée ainsi que la mesure des forces de contraction développées par les muscles extenseurs pour connaître le résultat de cette intervention après 14 à 36 mois.
Le membre droit (côté du prélèvement) était cliniquement normal à la fin de l’étude. L’étude électromyographique réalisée 14 jours après l’intervention chirurgicale a mis en évidence une dénervation à droite comme à gauche. Cette activité musculaire spontanée (avec fibrillation) disparaissait chez tous les chats à la fin de l’étude. La stimulation directe du rameau ventral de C8 à droite a permis de mettre en évidence une contraction des muscles du membre gauche chez tous les chats. Le ratio des forces de contraction du muscle extenseur radial du carpe gauche sur droit était proche de 1.
Cette étude expérimentale démontre que le transfert croisé du rameau ventral de C8 permet la ré-innervation du plexus controlatéral et la formation de nouvelles unités motrices avec réapparition d’une fonction sur un membre ayant subi une section de la partie caudale du plexus chez le chat.
Contralateral transfer of the right, eighth ventral nerve branch (C8) (C8 cross-transfer - C8CT) was performed in 6 adult cats, in which the caudal part of the left brachial plexus (C8 and T1) had been severed, in order to mimic nerve root avulsion.
Clinical and electrophysiological parameters, muscle contraction force measurements and histology were used to evaluate the effects of the surgery in a 14- to 36-month follow-up.
The right forelimb (donor side) was clinically normal (no lameness) in all the cats at the end of the study. Electromyography performed 14 days after surgery revealed denervation fibrillation potentials in both forelimbs. Fibrillation potentials disappeared in all the cats at the end of the study. Direct stimulation of the right C8 ventral branch induced motor and sensory evoked potentials in the left limb muscles in all the cats. The left to right contraction ratio of the extensor carpi radialis muscle was approximately 1.
This experimental study demonstrates that C8CT enables re-innervation of the contralateral brachial plexus and allows the establishment of new functional neuromuscular units. This can in turn enable the restoration of function, and could potentially lead to partial recovery after caudal brachial plexus avulsion in the cat.
Survival, regeneration and functional recovery of motoneurons after delayed reimplantation of avulsed spinal root in adult rat
2005, Experimental NeurologyWe have established that extensive reinnervation and functional recovery follow immediate reimplantation of avulsed ventral roots in adult rats. In the present study, we examined the consequences of reimplantation delayed for 2 weeks after avulsion of the C6 spinal root. Twelve and 20 weeks after delayed reimplantation, 57% and 53% of the motoneurons in the injured spinal segment survived. More than 80% of surviving motoneurons regenerated axons into the reimplanted spinal root. Cholinesterase–silver staining revealed axon terminals on endplates in the denervated muscles. The biceps muscles in reimplanted animals had atrophied less than those in animals with avulsion only, as indicated by muscle wet weight and histological appearance. After electrical stimulation of the motor cortex or the C6 spinal root, typical EMG signals were recorded in biceps of reimplanted animals. The latency of the muscle potential at 20 weeks was similar to that of sham-operated controls. Behavioral recovery was demonstrated by a grooming test and ipsilateral forepaw movements were well coordinated in both voluntary and automatic activities. These results demonstrate that ventral root reimplantation can protect severed motoneurons, enable the severed motoneurons to regenerate axons, and enhance the recovery of forelimb function even when it is delayed for 2 weeks after avulsion.