25th Anniversary of the Death of Nerve Surgery Pioneer Luis de Medinaceli

Our persistent inability to predictably restore function after nerve injury is one of the modern medicine's greatest shortcomings. And more urgently, it is the greatest impediment to satisfactory surgical outcomes in scenarios such as composite tissue allotransplantation (hands, faces, legs, etc.) and limb salvage after trauma. The French surgeon and researcher Luis de Medinaceli (1936–1996) was a remarkable man whose exquisite, methodical, and tragically underappreciated work in search of the means for improved nerve coaptation still remains in the shadows, 25 years after his untimely death ([Fig. 1]). It has never been more important that this man and his remarkable work be introduced to the current generation of surgeons and scientists.

Fig. 1 Luis de Medinaceli.

de Medinaceli was born in the Basque region in the south of France, and his surgical training and work subsequently took him to Paris, Algeria, the Caribbean islands of Dominica and Guadeloupe, Duke University, the National Institutes of Health, and ultimately back to France. Early in his career, he developed a passion for nerve restoration, and he developed the audacious goal of successfully repairing the injured spinal cord. This goal led him to the simple question that drove his life's work: how can function be restored after nerve transection?

Fundamentally, he appreciated that the necessary scale of repair was at the level of the axon. Instead of letting this cellular-level scale intimidate him or drive him away from attempting surgical repair, he systematically developed the necessary techniques and tools—both mechanical and chemical—to facilitate success at that very small scale. First, he developed and validated methods for trimming the cut nerve ends with minimal physical and chemical damages. For example, he found that by cryogenically freezing the nerve for a brief period and then cutting the nerve using an ultra-sharp vibrating blade, he could overcome the otherwise seemingly inevitable “sprouting” of axons that impeded functional recovery. Next, the ultra-clean-cut stumps could be coapted with the use of an antiretraction device he developed. This patented device allowed for the redistribution of tensile forces as the mechanical traction was kept a distance from each cut end. The new concept of axonal fusion being used today utilizes the method of blocking ion shifts to reduce chemical damage. It involved bathing the nerve in a solution similar to the fluid composition of the nerve and adding chlorpromazine for protection against free calcium ions. Microsurgical repair with minimal foreign body could then be performed expeditiously to minimize the degree of degradation and irreversible injury.[1] [2] But instead of simply focusing on the technical aspects of the repair, he honed a series of intraoperative chemical manipulations that could be used to both preserve the viability of the intracellular contents, as well as to greatly facilitate fusion at the level of each axon membrane.

de Medinaceli spent the majority of his research career in the United States, where he proudly became a naturalized American citizen. He published 33 peer-reviewed articles—including 4 in this journal—and all of his findings culminated in the masterful but still eminently readable textbook, Cell Surgery to Repair Divided Nerves [3] ([Fig. 2]). It unfortunately was rejected by every publisher he approached, so he was forced to resort to self-publication in 1994. It went largely unnoticed at the time of publication, is currently out of print, and today is nearly impossible to find. He developed the walking track method of analysis after nerve repair. According to de Medinaceli, gait could be utilized as an indicator for the accuracy of sciatic nerve injury axon repair; therefore, nerve function was able to be quantified based on the measurement of rat walking tracks in which gait is assessed in accordance with temporal and spatial relationship between each footprint. This methodology continues to be used to study neuronal injury and repair.[4]

Fig. 2 Cover of “Cell Surgery to Repair Divided Nerves” textbook, with representative figure.

de Medinaceli pursued his research up until the moment of his tragic and abrupt death in a car accident on a French highway on December 20, 1996. Though he had multiple collaborators throughout his career, few of his projects were continued, and thus at that moment most of the research he was pursuing ceased.

Though he is now gone, fortunately there are others who are pursuing the same lines of inquiry. George Bittner at the University of Texas at Austin was an early contemporary of de Medinaceli, and cited many of his publications in his own work. He is continuing to study the use of fusogenic chemicals such as polyethylene glycol to manipulate the chemical environment to improve nerve function after microsurgical repair of a transected nerve.[5] Additionally, Sergio Canavero in Italy and Ren Xiaoping in China are using chemical manipulation, clean cutting of the nerve stumps, and neuroprotective cooling in attempts to achieve neurologic recovery after head transplantation.[6]

History is full of remarkable individuals whose thoughts and work were ahead of his or her time, and who were thus never fully appreciated during his or her lifetime. Beginning almost 50 years ago, and up until the time of death, Luis de Medinaceli performed groundbreaking work that was ahead of its time then—and continues to be ahead of its time even today. As it is now 25 years since his personal ability to pursue his life's goal of complete restoration of function after nerve injury abruptly ended, it is more important than ever that his work be broadly known and appreciated, and hopefully, it will inspire others to continue where he left off.

Publication History

Received: 27 March 2021

Accepted: 31 May 2021

Article published online:
10 August 2021

• References

• 1 de Medinaceli L, Seaber AV. Experimental nerve reconnection: importance of initial repair. Microsurgery 1989; 10 (01) 56-70
• 2 de Medinaceli L, Merle M. How exact should nerve stump coaptation be? A new answer given by “cell surgery”. J Hand Surg [Br] 1991; 16 (05) 495-498
• 3 Medinaceli LD. Cell Surgery to Repair Divided Nerves. New York, NY: CASIS; 1994
• 4 de Medinaceli L, Wyatt RJ. Neurobehavioral evaluation of function following experimental nerve damage. Neurobehav Toxicol Teratol 1984; 6 (06) 415-417
• 5 Bittner GD, Sengelaub DR, Trevino RC. et al. The curious ability of polyethylene glycol fusion technologies to restore lost behaviors after nerve severance. J Neurosci Res 2016; 94 (03) 207-230
• 6 Ren X, Orlova EV, Maevsky EI, Bonicalzi V, Canavero S. Brain protection during cephalosomatic anastomosis. Surgery 2016; 160 (01) 5-10