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Allan H. Friedman, W. Jeffrey Elias and Rajiv Midha

Surgery aimed at repairing damaged peripheral nerves has a long history. Refuting the timehonored nihilism of Hippocrates and Galen that an injured nerve cannot regain function, a few adventurous medieval surgeons attempted to repair severed nerves.6,8 However, the ability of a peripheral nerve repair to restore function was not generally accepted until 1800.1,4 Neurosurgeons, beginning with Harvey Cushing, have had an interest in repairing damaged peripheral nerves.2 Significant progress in the treatment of peripheral nerve injuries resulted from experience with the numerous injuries that occurred during World Wars I and II.3,7,12 Surgeons steadily defined the anatomy of peripheral nerves and developed techniques for decompressing and repairing peripheral nerves.9,11 Kline and Dejonge5 developed an intraoperative electrophysiological technique for detecting axons regenerating across a damaged segment of nerve. In the second 2 decades of the 20th century, distal nerve transfers were rediscovered whereby the proximal end of a less essential nerve is used to reinnervate the distal end of a nerve, providing a more vital function.10

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Rajiv Midha

Nerve transfer procedures are increasingly performed for repair of severe brachial plexus injury (BPI), in which the proximal spinal nerve roots have been avulsed from the spinal cord. The procedure essentially involves the coaption of a proximal foreign nerve to the distal denervated nerve to reinnervate the latter by the donated axons. Cortical plasticity appears to play an important physiological role in the functional recovery of the reinnervated muscles. The author describes the general principles governing the successful use of nerve transfers. One major goal of this literature review is to provide a comprehensive survey on the numerous intra- and extraplexal nerves that have been used in transfer procedures to repair the brachial plexus. Thus, an emphasis on clinical outcomes is provided throughout. The second major goal is to discuss the role of candidate nerves for transfers in the surgical management of the common severe brachial plexus problems encountered clinically. It is hoped that this review will provide the treating surgeon with an updated list, indications, and expected outcomes involving nerve transfer operations for severe BPIs.

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Vanessa J. Sammons and Rajiv Midha

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Surgery for nerve injury: current and future perspectives

JNSPG 75th Anniversary Invited Review Article

Rajiv Midha and Joey Grochmal

In this review article, the authors offer their perspective on nerve surgery for nerve injury, with a focus on recent evolution of management and the current surgical management. The authors provide a brief historical perspective to lay the foundations of the modern understanding of clinical nerve injury and its evolving management, especially over the last century. The shift from evaluation of the nerve injury using macroscopic techniques of exploration and external neurolysis to microscopic interrogation, interfascicular dissection, and internal neurolysis along with the use of intraoperative electrophysiology were important advances of the past 50 years. By the late 20th century, the advent and popularization of interfascicular nerve grafting techniques heralded a major advance in nerve reconstruction and allowed good outcomes to be achieved in a large percentage of nerve injury repair cases. In the past 2 decades, there has been a paradigm shift in surgical nerve repair, wherein surgeons are not only directing the repair at the injury zone, but also are deliberately performing distal-targeted nerve transfers as a preferred alternative in an attempt to restore function. The peripheral rewiring approach allows the surgeon to convert a very proximal injury with long regeneration distances and (often) uncertain outcomes to a distal injury and repair with a greater potential of regenerative success and functional recovery. Nerve transfers, originally performed as a salvage procedure for severe brachial plexus avulsion injuries, are now routinely done for various less severe brachial plexus injuries and many other proximal nerve injuries, with reliably good to even excellent results. The outcomes from nerve transfers for select clinical nerve injury are emphasized in this review. Extension of the rewiring paradigm with nerve transfers for CNS lesions such as spinal cord injury and stroke are showing great potential and promise. Cortical reeducation is required for success, and an emerging field of rehabilitation and restorative neurosciences is evident, which couples a nerve transfer procedure to robotically controlled limbs and mind-machine interfacing. The future for peripheral nerve repair has never been more exciting.

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Mustafa Nadi, Sudheesh Ramachandran, Abir Islam, Joanne Forden, Gui Fang Guo and Rajiv Midha

OBJECTIVE

Supercharge end-to-side (SETS) transfer, also referred to as reverse end-to-side transfer, distal to severe nerve compression neuropathy or in-continuity nerve injury is gaining clinical popularity despite questions about its effectiveness. Here, the authors examined SETS distal to experimental neuroma in-continuity (NIC) injuries for efficacy in enhancing neuronal regeneration and functional outcome, and, for the first time, they definitively evaluated the degree of contribution of the native and donor motor neuron pools.

METHODS

This study was conducted in 2 phases. In phase I, rats (n = 35) were assigned to one of 5 groups for unilateral sciatic nerve surgeries: group 1, tibial NIC with distal peroneal-tibial SETS; group 2, tibial NIC without SETS; group 3, intact tibial and severed peroneal nerves; group 4, tibial transection with SETS; and group 5, severed tibial and peroneal nerves. Recovery was evaluated biweekly using electrophysiology and locomotion tasks. At the phase I end point, after retrograde labeling, the spinal cords were analyzed to assess the degree of neuronal regeneration. In phase II, 20 new animals underwent primary retrograde labeling of the tibial nerve, following which they were assigned to one of the following 3 groups: group 1, group 2, and group 4. Then, secondary retrograde labeling from the tibial nerve was performed at the study end point to quantify the native versus donor regenerated neuronal pool.

RESULTS

In phase I studies, a significantly increased neuronal regeneration in group 1 (SETS) compared with all other groups was observed, but with modest (nonsignificant) improvement in electrophysiological and behavioral outcomes. In phase II experiments, the authors discovered that secondary labeling in group 1 was predominantly contributed from the donor (peroneal) pool. Double-labeling counts were dramatically higher in group 2 than in group 1, suggestive of hampered regeneration from the native tibial motor neuron pool across the NIC segment in the presence of SETS.

CONCLUSIONS

SETS is indeed an effective strategy to enhance axonal regeneration, which is mainly contributed by the donor neuronal pool. Moreover, the presence of a distal SETS coaptation appears to negatively influence neuronal regeneration across the NIC segment. The clinical significance is that SETS should only employ synergistic donors, as the use of antagonistic donors can downgrade recovery.

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Sarah Walsh, and Rajiv Midha

In this review the authors intend to demonstrate the need for supplementing conventional repair of the injured nerve with alternative therapies, namely transplantation of stem or progenitor cells. Although peripheral nerves do exhibit the potential to regenerate axons and reinnervate the end organ, outcome following severe nerve injury, even after repair, remains relatively poor. This is likely because of the extensive injury zone that prevents axon outgrowth. Even if outgrowth does occur, a relatively slow growth rate of regeneration results in prolonged denervation of the distal nerve. Whereas denervated Schwann cells (SCs) are key players in the early regenerative success of peripheral nerves, protracted loss of axonal contact renders Schwann cells unreceptive for axonal regeneration. Given that denervated Schwann cells appear to become effete, one logical approach is to support the distal denervated nerve environment by replacing host cells with those derived exogenously. A number of different sources of stem/precursor cells are being explored for their potential application in the scenario of peripheral nerve injury. The most promising candidate, transplant cells are derived from easily accessible sources such as the skin, bone marrow, or adipose tissue, all of which have demonstrated the capacity to differentiate into Schwann cell–like cells. Although recent studies have shown that stem cells can act as promising and beneficial adjuncts to nerve repair, considerable optimization of these therapies will be required for their potential to be realized in a clinical setting. The authors investigate the relevance of the delivery method (both the number and differentiation state of cells) on experimental outcomes, and seek to clarify whether stem cells must survive and differentiate in the injured nerve to convey a therapeutic effect. As our laboratory uses skin-derived precursor cells (SKPCs) in various nerve injury paradigms, we relate our findings on cell fate to other published studies to demonstrate the need to quantify stem cell survival and differentiation for future studies.

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Shelly Lwu and Rajiv Midha

✓A thorough history and physical examination are fundamental to the assessment of patients with brachial and pelvic plexus tumors. Typical of most peripheral nerve tumors, the presenting symptoms and signs are few, and if present, can be subtle. Presenting complaints may include a palpable mass lesion, either symptomatic or asymptomatic; sensory alterations; pain; motor deficits; visceral symptoms; or autonomic dysfunction. Motor deficits are usually a late feature in the pathogenesis of this lesion, and a progressive course of pain and significant sensory and motor deficits suggests a malignant pathological process. A detailed family history may reveal familial syndromes and neurocutaneous disorders that predispose the patient to neoplasia, such as neurofibromatosis. The physical examination should be conducted in a systematic fashion, looking for any cutaneous features and motor and sensory deficits. The mass should also be examined for form, consistency, and mobility. An irregular, firm, and immobile mass suggests a malignant lesion. Complete and accurate clinical information must be gathered to pinpoint the anatomical localization of the lesion and formulate a differential diagnosis.

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Tarek EI Madhoun and Rajiv Midha

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David G. Kline, Daniel Kim, Rajiv Midha, Carter Harsh and Robert Tiel

Object. The purpose of this retrospective clinical study was to present results and provide management guidelines for various types of sciatic injuries.

Methods. Over a 24-year period, 380 patients with sciatic nerve injuries were managed. In 230 patients (60%), the injury was at the buttock level, with injection injuries comprising more than half of these cases. Thigh-level sciatic injury was evaluated in 150 cases (40%) and was usually secondary to one of four main causes: 1) gunshot wound; 2) femur fracture; 3) laceration; or 4) contusion. Patients with partial deficits uncomplicated by severe pain or with significant spontaneous recovery or late referral were managed medically. Surgical exploration was not indicated in 23% of injuries at the thigh level and almost 50% of those at the buttock level. Most of these patients achieved partial but good spontaneous recovery, especially in the tibial division distribution. Surgical intervention was required for more complete and persistent deficits in either the tibial or peroneal distribution. Divisions of the sciatic nerve were split apart and evaluated independently. Management was guided by nerve action potential (NAP) recordings, which indicated whether neurolysis or resection of the lesion was required. Repair was then made by using sutures or more frequently by graft placement.

In most cases in which neurolysis was performed because a positive NAP was recorded distal to the lesion, useful function was found in the peroneal distribution. Unfortunately, significant recovery occurred in only 36% of patients who received suture or graft repairs of the peroneal division. Good-to-excellent outcome was common for the tibial division, even in cases in which repair was proximal and required lengthy grafts. The relatively favorable recovery of tibial as opposed to peroneal divisions of the sciatic nerve occurred regardless of the level or mechanism of injury.

Conclusions. Surgical exploration and, when necessary, repair of sciatic nerve injuries is worthwhile in selected cases.