Introduction: reconstructive microsurgery in Italy.
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Publications and source records attributed to Bruno Battiston.
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Diagnosis becomes more complex when there is an association of a brachial plexus injury with an arterial lesion. The principal clinical picture in most cases is acute ischemia that requires initial treatment in the emergency room, and the final results of nerve repair are generally poorer. Although delayed brachial plexus reconstruction is preferred by some authors, our experience leads us to the opinion that a combined repair presents several advantages. Immediately after trauma, the surgical field is free of scar tissue, and a precise evaluation of both the number and level of damaged nerves may be made. Vascular and nerve repair may be mutually agreed upon by both the vascular surgeon and microsurgeon, and simple sutures may often be used instead of grafts in early nerve repair. Even if the extent of nerve damage may sometimes be difficult to assess, the results of early, easier repairs can be observed in our series of 14 combined lesions. Our results indicate that collaboration between microsurgeons and vascular surgeons is a very important factor in providing a correct approach to these problematic patients.
Schwann cells play a critical role in peripheral nerve regeneration. When a non-nervous conduit is used to bridge a nerve defect, the conduit is soon colonized by a number of Schwann cells that make a pathway for regrowing axons. By using electron microscopy, immunohistochemistry, and reverse transcriptase-polymerase chain reaction analysis, we have investigated the behavior of migratory glial cells along a particular type of autologous tissue-engineered conduit made of a vein filled with fresh skeletal muscle, using the rat sciatic nerve model. With this particular type of autograft, our data show that many Schwann cells soon take up a close relationship with grafted muscle fibers, and especially with their basal lamina, which appears to serve as a migration pathway for them. The early and massive colonization of the conduit is sustained by both Schwann cell migration and proliferation, as demonstrated by PCNA immunostaining. Later, as they meet regenerating axons, Schwann cells become closely associated with them and eventually lose their connections with grafted muscle fibers because of the formation of perineurial envelopes. Because previous studies showed that alpha(2a-2b) NRG1 is overexpressed at early stages along the muscle-vein combined tubes, we have also investigated mRNA expression of its two receptors, erbB2 and erbB3. Both messengers are overexpressed, although with different time courses. Overall, our results provide some morphological and biochemical bases for explaining the effectiveness of fresh muscle-vein combined nerve guides and throw an interesting light on the possible role of alpha(2a-2b) NRG1 through the erbB2/erbB3 heterodimer receptor for nerve regeneration inside non-nervous conduits.
Nerve repair is usually accomplished by direct suture when the two stumps can be approximated without tension. In the presence of a nerve defect, the placement of an autologous nerve graft is the current gold standard for nerve restoration. However, over the last 20 years, an increasing number of research articles reported on the use of non-nervous tubes (tubulization) for repairing nerve defects. The clinical employment of tubes (both biological and synthetic) as an alternative to autogenous nerve grafts is mainly justified by the limited availability of donor tissue for nerve autografts and the related morbidity. In addition, tubulization was proposed as an alternative to direct nerve sutures in order to create optimal conditions for nerve regeneration over the short empty space intentionally left between two nerve stumps. This paper outlines recent important advances in this field. Different tubulization techniques proposed so far are described, focusing in particular on studies that reported on the employment of tubes with patients. Our personal clinical experience on tubulization repair of sensory nerve lesions (digital nerves), using both biological and synthetic tubes, is presented, and the clinical results are compared. In our case series, both types of tubes led to good clinical results. Finally, we speculate about the prospects in the clinical application of tubulization for peripheral nerve repair.
Facial nerve reconstruction for lesions with nerve gaps frequently require autologous or tubulized grafts of biological or synthetic origin. Neurotube, a bioabsorbable polyglycolic acid tube, represents a valid solution for this kind of defect in emergency and planned surgery. Seven posttraumatic lesions of terminal branches of the facial nerve were repaired by means of Neurotube from September 1999-September 2001. The nerve gap size ranged between 1-3 cm. Nerve regeneration was evaluated at 7-12 months of follow-up when muscle recovery function was examined. Muscle function was very good in 1 case, good in 4, and fair in 2 (71% positive results). No intolerance or discomfort was reported or observed. Neurotube is useful for the reconstruction of facial nerve lesions with a small nerve gap (less then 3 cm) when a direct anastomosis of the two stumps is not possible, or when the suture appears to be in tension. It is a valid alternative to autologous and biological tubulized grafts. The limits of this method are: 1) it can only be used with gaps of less than 3 cm; 2) it is quite costly; 3) there are reports of possible intolerance; and 4) it is not suitable for lesions of the proximal part of the facial nerve.
Y-shaped vein conduits enriched with fresh skeletal muscle fibers were used to bridge a concomitant ulnar and median nerve transection with substance loss in rats. The proximal limb of the Y-chamber was sutured to the proximal ulnar nerve, while the two distal limbs were sutured to ulnar and median distal nerve stumps. Eight months after surgery, median nerve functional recovery was evaluated by means of the grasping test, and nerve fiber regeneration in both repaired nerves was assessed by means of design-based histomorphometry. Results showed that nerve fibers regenerated along both severed nerve trunks, and in the median nerve led to a recovery corresponding to 58% of normal nerve function. Quantitative analysis showed no significant morphological differences between myelinated nerve fibers regenerated along the two distal nerves except for the number of fibers, which was higher in the median nerve. Notably, the total number of regenerated nerve fibers in the two distal nerves was 4-fold the normal fiber number in the ulnar nerve. Besides their interest in relation to the long-lasting debate about the topographic specificity of nerve regeneration, the results of this study show an effective way to repair, in the rat experimental model, two transected nerve trunks innervating agonistic muscles in the case that the proximal stump of only one nerve is preserved.
Various tubulization techniques can be used to bridge peripheral nerve lesions with substance loss. Among the different materials that have been used so far in alternative to traditional fresh nerve autografts, fresh muscle-vein combined conduits (made by a vein segment filled with fresh skeletal muscle) proved to be particularly effective. In this study, nerve repair of 10-mm long nerve defects by means of muscle-vein combined tubes was compared with repair by means of traditional nerve autografts in the rat sciatic nerve experimental model. Results did not reveal any significant difference between the two groups of regenerated nerves with respect to the total number, mean density and mean size of myelinated nerve fibers. In addition, we also report the results of an experimental study in the rabbit sciatic nerve model, which showed that fresh skeletal muscle enrichment of the vein segment made it possible to bridge 55-mm long nerve gaps. These results provide further evidence of the effectiveness of fresh muscle-vein combined grafts and support the view that this type of conduit can be used also for repairing long nerve gaps.
Using RT-PCR, we have investigated expression of isoforms beta1 (the axonal isoform) and alpha2a-2b (the mesenchymal isoform) of neuregulin-1, one of the most important known trophic factors for Schwann cells, in the rat sciatic nerve repaired by muscle-enriched non-nervous conduits (made by a vein filled with fresh skeletal muscle). Repaired nerves were harvested 2, 6 and 13 days post-operatively. Results showed that while muscle-vein combined grafts were enriched in mRNA coding for alpha2a-2b since the very early regeneration stages, isoform beta1 mRNA was not detectable inside the tubes at day 2 and 6 post-operatively while its expression at day 13 was very slight. These results suggest that Schwann cell survival and activity inside a fresh muscle-enriched non-nervous conduit graft (a key factor for successful nerve regeneration along the graft) may be supported by the mesenchymal isoform of neuregulin-1 during very early repair phases, i.e. when axons are still not present along the tube.
The quantitative assessment of motor function is an important requirement for studies on peripheral nerve injury and repair. So far, most studies on peripheral nerves have been performed on the sciatic nerve model using walking track analysis for assessing motor function. Alternatively, the employment of the median nerve model, which allows motor function evaluation by means of a simple behavioural test named grasping test (GT), have been more recently proposed. In this paper, the efficacy of the GT for the quantitative assessment of motor function recovery is re-appraised and a modified device for its carrying out is described. Finally, the rationale for the employment of the median nerve model as an alternative to the sciatic nerve model is critically discussed.
While it has been shown that terminolateral (end-to-side) neurorrhaphy leads to successful functional motor reinnervation of the peripheral territories belonging to the severed nerve, data on the morphology of terminolateral sprouting and on the voluntary control of the motor function restored by terminolateral neurorrhaphy are still partial. In this study, the severed rat median nerve was sutured in an end-to-side fashion to the intact ulnar nerve. The progression of recovery of the flexion of the fingers was assessed by means of the grasping test. Seven months after surgery, the rats were sacrificed, and morphologic and morphometric analysis was performed on the regenerated median nerve and on the donor ulnar nerve. Results of the functional assessment showed that voluntary motor control of the muscles innervated by the median nerve was partially and progressively recovered by terminolateral neurorrhaphy, with a mean strength in the flexion of the fingers that reached about 20 percent of normal before sacrifice. Morphologic and morphometric analysis showed that nerve-fiber regeneration occurred in all repaired median nerves. Signs of nerve fiber atrophy were detected in the ulnar nerve distal to the point of suture, suggesting the possible occurrence of secondary damage to the donor nerve after terminolateral neurorrhaphy that should be taken into consideration in a clinical perspective.
Experimental and clinical studies have shown that a vein segment filled with skeletal muscle used to bridge a peripheral nerve defect (muscle-vein-combined graft) leads to good nerve repair. However, the molecular basis of the nerve fiber regeneration process along this type of graft still remains to be elucidated. The aim of this study was to verify the expression of two neurotrophins, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), as well as their receptors, trkA and p75, in an early stage of axonal regeneration in muscle-vein-combined grafts. Severed rat sciatic nerves were repaired by means of 1-cm-long muscle-vein-combined grafts and withdrawn immediately after surgery (control grafts) and 5 days after surgery. Longitudinal sections of grafts were immunostained by means of the following antibodies: anti-NGF, anti-BDNF, anti-trkA, and anti-p75. An anti-glial fibrillar acid protein (anti-GFAP) antibody was used to recognize Schwann cells. Results showed the presence of a number of GFAP-positive Schwann cells inside the muscle-vein grafts. Many of these cells reacted for NGF, BDNF, and p75, but not trkA. In control grafts, i.e., immediately after surgery, no immunostaining was detected for any of the antibodies used in this study. These observations suggest that, very early after surgery, the muscle-vein-combined graft offers to growing axons an environment particularly favorable for regeneration, providing us with a possible explanation for the efficacy of this grafting technique for peripheral nerve repair.
The need for reconstruction of lower limb amputations is increasing, due to high-energy trauma in road accidents and work-related injuries. The indication for lower limb replantation is still controversial. Compared with upper limb replantations, indications are more select due to the frequent complications in lower limb salvage procedures, such as severe general complications or local complications such as necrosis, infections, nonunions, the need for secondary lengthening, or other reconstructive procedures. The satisfactory results given by artificial prosthesis, such as quicker recovery time and fewer secondary procedures, also contribute to the higher degree of selection for lower limb replantation candidates. Since 1993, we have replanted 14 amputations of the lower limb in 12 patients, including 2 bilateral cases. Although survival of the replanted segment was obtained in all patients, 5 cases were subsequently amputated for severe secondary complications. Of the remaining 9 cases, evaluated by means of Chen criteria, 7 had good results (3 Chen I and 4 Chen II), 1 sufficient (Chen III), and 1 poor (Chen IV). The best results were obtained in young patients. Our experience led us to examine the necessity for careful, objective patient selection. We developed a score evaluation system by modifying the international classifying method for severe limb traumas (mangled extremity severity score, or MESS system). This relatively simple system, based on the retrospective study of our cases, considers several parameters (patient's age, general conditions, level and type of lesion, time of injury, and associated lesions), giving each one a score. The total score gives the indication for replantation, predicts the functional outcome, and facilitates decision-making.
Current medical nomenclature is often based on the early history of the condition, when the true etiology of the disease or condition was not known. Sadly, this incorrect terminology can become inextricably woven into the lexicon of mainstream medicine. More important, when this is the case, the terminology itself can become integrated into current clinical decision making and ultimately into surgical intervention for the condition. "Morton's neuroma" is perhaps the most striking example of this nomenclature problem in foot and ankle surgery. We aimed to delineate the historical impetus for the terminology still being used today for this condition and to suggest appropriate terminology based on our current understanding of its pathogenesis. We concluded that this symptom complex should be given the diagnosis of nerve compression and be further distinguished by naming the involved nerve, such as compression of the interdigital nerve to the third web space or compression of the third common plantar digital nerve. Although the nomenclature becomes longer, the pathogenesis is correct, and treatment decisions can be made accordingly.