Stretch injuries are among the most devastating forms of peripheral nerve injury; unfortunately, the scientific understanding of nerve biomechanics is widely and impressively conflicting. Experimental models are unique and disparate, victim to different testing conditions, and thus yield gulfs between conclusions. The details of the divergent reports on nerve biomechanics are essential for critical appraisal as we try to understand clinical stretch injuries in light of research evidence. These conflicts preclude broad conclusion, but they highlight a duality in thought on nerve stretch and, within the details, some agreement exists. To synthesize trends in nerve stretch understanding, the author describes the literature since its introduction in the 19th century. Research has paralleled clinical inquiry, so nerve research can be divided into epochs based largely on clinical or scientific technique. The first epoch revolves around therapeutic nerve stretching—a procedure known as neurectasy—in the late 19th century. The second epoch involves studies of nerves repaired under tension in the early 20th century, often the result of war. The third epoch occurs later in the 20th century and is notable for increasing scientific refinement and disagreement. A fourth epoch of research from the 21st century is just dawning. More than 150 years of research has demonstrated a stable and inherent duality: the terribly destructive impact of stretch injuries, as well as the therapeutic benefits from nerve stretching. Yet, despite significant study, the precise border between safe and damaging stretch remains an enigma.
Mark A. Mahan
Stewart Yeoh, Wesley S. Warner, Ilyas Eli, and Mark A. Mahan
Traditional animal models of nerve injury use controlled crush or transection injuries to investigate nerve regeneration; however, a more common and challenging clinical problem involves closed traction nerve injuries. The authors have produced a precise traction injury model and sought to examine how the pathophysiology of stretch injuries compares with that of crush and transection injuries.
Ninety-five late-adolescent (8-week-old) male mice underwent 1 of 7 injury grades or a sham injury (n > 10 per group): elastic stretch, inelastic stretch, stretch rupture, crush, primary coaptation, secondary coaptation, and critical gap. Animals underwent serial neurological assessment with sciatic function index, tapered beam, and von Frey monofilament testing for 48 days after injury, followed by trichrome and immunofluorescent nerve histology and muscle weight evaluation.
The in-continuity injuries, crush and elastic stretch, demonstrated different recovery profiles, with more severe functional deficits after crush injury than after elastic stretch immediately following injury (p < 0.05). However, animals with either injury type returned to baseline performance in all neurological assessments, accompanied by minimal change in nerve histology. Inelastic stretch, a partial discontinuity injury, produced more severe neurological deficits, incomplete return of function, 47% ± 9.1% (mean ± SD) reduction of axon counts (p < 0.001), and partial neuroma formation within the nerve. Discontinuity injuries, including immediate and delayed nerve repair, stretch rupture, and critical gap, manifested severe, long-term neurological deficits and profound axonal loss, coupled with intraneural scar formation. Although repaired nerves demonstrated axon regeneration across the gap, rupture and critical gap injuries demonstrated negligible axon crossing, despite rupture injuries having healed into continuity.
Stretch-injured nerves present unique pathology and functional deficits compared with traditional nerve injury models. Because of the profound neuroma formation, stretch injuries represent an opportunity to study the pathophysiology associated with clinical injury mechanisms. Further validation for comparison with human injuries will require evaluation in a large-animal model.
Hussam Abou-Al-Shaar and Mark A. Mahan
Endoscopic surgery has revolutionized the field of minimally invasive surgery. Nerve injury after laparoscopic surgery is presumably rare, with only scarce reports in the literature; however, the use of these techniques for new purposes presents the opportunity for novel complications. The authors report a case of subcostal nerve injury after an anterior laparoscopic approach to a posterior abdominal wall lipoma.
A 62-year-old woman presented with a left abdominal flank bulge (pseudohernia) that developed after laparoscopic posterior flank wall lipoma resection. Imaging demonstrated frank ballooning of the oblique muscles; denervation atrophy and thinning of the external oblique, internal oblique, and transverse abdominis muscles; and thinning of the rectus abdominis muscle. The patient underwent subcostal nerve repair and removal of a foreign plastic material from the laparoscopic procedure. At 8 months, she has regained substantial improvement in abdominal wall strength.
Although endoscopic procedures have resulted in significant reduction in morbidity, “minimally invasive” approaches should not be confused with “low risk” when approaching novel pathology. The subcostal nerve is at risk of injury in posterior abdominal wall surgery, whether laparoscopic or not. With the pseudohernia and abdominal bulge after this surgery, the cosmetic appeal of laparoscopic incisions was definitively undone. Selecting an approach based on the anatomy of adjacent structures may lead to a better functional result.
Mark A. Mahan, Kimberly K. Amrami, and Robert J. Spinner
Stewart Yeoh and Mark A. Mahan
Hussam Abou-Al-Shaar, Nam Yoon, and Mark A. Mahan
Traumatic proximal sciatic nerve rupture poses surgical repair dilemmas. Disruption often causes a large nerve gap after proximal neuroma and distal scar removal. Also, autologous graft material to bridge the segmental defect may be insufficient, given the sciatic nerve diameter. The authors utilized knee flexion to allow single neurorrhaphy repair of a large sciatic nerve defect, bringing healthy proximal stump to healthy distal segment. To avoid aberrant regeneration, the authors split the sciatic nerve into common peroneal and tibial divisions. After 3 months, the patient can fully extend the knee and has evidence of distal regeneration and nerve continuity without substantial injury.
The video can be found here: https://youtu.be/lsezRT5I8MU.
Mark A. Mahan, Wesley S. Warner, Stewart Yeoh, and Alan Light
Rapid-stretch nerve injuries are among the most devastating lesions to peripheral nerves, yielding unsatisfactory functional outcomes. No animal model has yet been developed that uses only stretch injury for investigation of the pathophysiology of clinical traction injuries. The authors’ objective was to define the behavioral and histopathological recovery after graded rapid-stretch nerve injury.
Four groups of male B6.Cg-Tg(Thy1-YFP)HJrs/J mice were tested: sham injury (n = 11); stretch within elastic limits (elastic group, n = 14); stretch beyond elastic limits but before nerve rupture (inelastic group, n = 14); and stretch-ruptured nerves placed in continuity (rupture group, n = 16). Mice were injured at 8 weeks of age, comparable with human late adolescence. Behavioral outcomes were assessed using the sciatic functional index (SFI), tapered-beam dexterity, Von Frey monofilament testing, and the Hargreaves method. Nerve regeneration outcomes were assessed by wet muscle weight and detailed nerve histology after 48 days.
Post hoc biomechanical assessment of strain and deformation confirmed that the differences between the elastic and inelastic cohorts were statistically significant. After elastic injury, there was a temporary increase in foot faults on the tapered beam (p < 0.01) and mild reduction in monofilament sensitivity, but no meaningful change in SFI, muscle weight, or nerve histology. For inelastic injuries, there was a profound and maintained decrease in SFI (p < 0.001), but recovery of impairment was observed in tapered-beam and monofilament testing by days 15 and 9, respectively. Histologically, axon counts were reduced (p = 0.04), muscle atrophy was present (p < 0.01), and there was moderate neuroma formation on trichrome and immunofluorescent imaging. Stretch-ruptured nerves healed in continuity but without evidence of regeneration. Substantial and continuous impairment was observed in SFI (p < 0.001), tapered beam (p < 0.01), and monofilament (p < 0.01 until day 48). Axon counts (p < 0.001) and muscle weight (p < 0.0001) were significantly reduced, with little evidence of axonal or myelin regeneration concurrent with neuroma formation on immunofluorescent imaging.
The 3 biomechanical grades of rapid-stretch nerve injuries displayed consistent and distinct behavioral and histopathological outcomes. Stretch within elastic limits resembled neurapraxic injuries, whereas injuries beyond elastic limits demonstrated axonotmesis coupled with impoverished regeneration and recovery. Rupture injuries uniquely failed to regenerate, despite physical continuity of the nerve. This is the first experimental evidence to correlate stretch severity with functional and histological outcomes. Future studies should focus on the pathophysiological mechanisms that reduce regenerative capacity after stretch injury.
Tomas Marek, Robert J. Spinner, Akshay Syal, and Mark A. Mahan
Lipomatosis of nerve (LN) is a massive enlargement of a nerve due to abundant proliferation of adipose and fibrotic tissue within the epineurium—part of the spectrum of adipose lesions of nerves, including intra- and extraneural lipomas. LN has been frequently associated with soft-tissue and/or osseous overgrowth. Unfortunately, much confusion exists since many names have been used for LN (e.g., fibrolipomatous hamartoma, macrodystrophia lipomatosa, and so on). To better understand this condition and to evaluate its association with nerve-territory overgrowth, the authors attempted to compile the world’s literature on published LN cases.
PubMed and Google Scholar databases were searched to identify published articles on LN cases, using a variety of terms. Publications in all languages were assessed. All publications with cases determined likely to be LN were read. Cases that provided clear clinicopathological and/or radiological evidence of LN were labeled as “definite” and cases that demonstrated features of LN (e.g., nerve-territory overgrowth) but lacked definite proof of nerve involvement were labeled as “probable.”
Initial screening revealed a total of 2465 papers. After exclusions, 281 publications reported cases with a definite diagnosis of LN and 120 articles reported cases with a probable diagnosis of LN. The authors identified 618 definite and 407 probable cases of LN. Sex distribution was balanced (51% female). Early diagnosis was common, with two-thirds of patients having symptoms in the 1st decade of life. The most commonly affected nerve was the median nerve (n = 391). Nerve-territory overgrowth was common (62% definite LN; 78% combined cases); overgrowth was exclusive to the territory of the affected nerve in all cases but 5.
The authors present a comprehensive review and analysis of the literature of LN cases. One of the main findings was the nerve-territory overgrowth was associated with LN, especially when present earlier in life. The authors believe that all cases of LN associated with overgrowth can be explained on anatomical grounds, even in the few reported cases in which this is not immediately obvious.
Mark A. Mahan, Jaime Gasco, David B. Mokhtee, and Justin M. Brown
Surgical transposition of the ulnar nerve to alleviate entrapment may cause otherwise normal structures to become new sources of nerve compression. Recurrent or persistent neuropathy after anterior transposition is commonly attributable to a new distal compression. The authors sought to clarify the anatomical relationship of the ulnar nerve to the common aponeurosis of the humeral head of the flexor carpi ulnaris (FCU) and flexor digitorum superficialis (FDS) muscles following anterior transposition of the nerve.
The intermuscular septa of the proximal forearm were explored in 26 fresh cadaveric specimens. The fibrous septa and common aponeurotic insertions of the flexor-pronator muscle mass were evaluated in relation to the ulnar nerve, with particular attention to the effect of transposition upon the nerve in this region.
An intermuscular aponeurosis associated with the FCU and FDS muscles was present in all specimens. Transposition consistently resulted in angulation of the nerve during elbow flexion when this fascial septum was not released. The proximal site at which the nerve began to traverse this fascial structure was found to be an average of 3.9 cm (SD 0.7 cm) from the medial epicondyle.
The common aponeurosis encountered between the FDS and FCU muscles represents a potential site of posttransposition entrapment, which may account for a subset of failed anterior transpositions. Exploration of this region with release of this structure is recommended to provide an unconstrained distal course for a transposed ulnar nerve.
Justin M. Brown, Mark A. Mahan, Ross Mandeville, and Bob S. Carter
Neurosurgery is experiencing the emergence of a new subspecialty focused on function restoration. New, evolving, and reappraised surgical procedures have provided an opportunity to restore function to many patients with previously undertreated disorders. Candidates for reconstruction were previously limited to those with peripheral nerve and brachial plexus injuries, but this has been expanded to include stroke, spinal cord injury, and a host of other paralyzing disorders affecting both upper and lower motor neurons. Similar to the recent evolution of the well-established subdisciplines of spinal and vascular neurosurgery, reconstructive neurosurgery requires the adaptation of techniques and skills that were not traditionally a part of neurosurgical training. Neurosurgeons—as the specialists who already manage this patient population and possess the requisite surgical skills to master the required techniques—have a unique opportunity to lead the development of this field. The full development of this subspecialty will lay the foundation for the subsequent addition of emerging treatments, such as neuroprosthetics and stem cell–based interventions. As such, reconstructive neurosurgery represents an important aspect of neurosurgical training that can ameliorate many of the deficits encountered in the traditional practice of neurosurgery.