Abstract
Dear Sir,
We read this article with great interest. First of all we would like to thank the authors for their extensive and honest overview of their results. Some statements, however, may benefit from additional information, or should be placed in perspective.
The 28 nerve guides were used for six different locations in the body for reconstruction of different peripheral nerves. We would encourage the authors to present digital and mixed nerves separately. In addition, almost one-third of the reconstructions had a follow-up of nine months or less. This makes drawing conclusions difficult, as mixed nerves need longer to recover.
Two patients had protrusion of a Neurolac™ nerve guide. In one of these patients the nerve defect was, therefore, reconstructed further using a nerve graft. This patient is summarized in one the tables with a follow up of 30 months and a static two point discrimination (s2PD) of >30 mm. In fact, this is the s2PD after secondary reconstruction with a nerve graft, not after a Neurolac™ nerve guide.
Chiriac and colleagues discussed whether or not protrusion in 2/28 of their patients was caused by a foreign body reaction against the biomaterial. We do not believe that was the reason. In fact, the authors mentioned in their results that both nerve guides were located on the palmar surface of a digital joint. This was also the case in the articles of Hernández-Cortés, Mackinnon, and Meek (Hernández-Cortés et al., 2010; Mackinnon and Dellon, 1990; Meek, 2007). So it may be that forces induced by flexion and (hyper)extension of a joint may have a detrimental effect.
Another negative influence may be the quality of soft tissue cover. In the Neurolac™ randomized prospective multicenter study two nerve guides (of 35 nerve reconstructions with nerve guides) protruded, one owing to infection and one owing to wound dehiscence (Meek et al., 2005). Weber mentioned that all three (of 46 nerve reconstructions with nerve guides) protrusions developed because of the poor quality of the skin overlying the tube (Weber et al., 2000). Protrusion is not related to just Neurolac™ nerve guides alone. In Weber’s article, 3/46 of the Poly Glycolic acid (PGA) neurotubes protruded and in Mackinnon’s article 1/15 neurotubes protruded.
Chiriac and colleagues believed there was a bias in the article of Bertleff et al. with regard to the distance from the lesion to the fingertip in the Neurolac™ and control group (Bertleff et al., 2005). Data were analysed statistically by an independent data management office. There was no difference between both groups and Bertleff’s statement was correct. However, there was another bias. It was mentioned that ‘the gap length (distance between the proximal and distal stumps) was measured with the fingers fully extended’ and after randomization into the Neurolac™ nerve guide group or the control group, ‘It was up to the surgeon to decide to use a nerve graft in case the gap length was too large.’ (Bertleff et al., 2005). The results of the entire study were presented during the 2005 meeting of the American Society for Peripheral Nerve (Meek et al., 2005). In total, 54 patients were enrolled in the study, of whom 30 were implanted with a Neurolac™ nerve guide. The control group consisted of 24 patients. In all controls, except two, the surgeons chose to repair the defect with an epineurial suturing technique. In only two cases a nerve graft was used. So although the study set-up was exactly the same as Weber’s study, the final outcome was actually a comparison between a group of nerve guides and direct nerve repair under tension. Although this was not foreseen, from a scientific point of view it may be of interest.
In Weber’s study, however, a gap length of 8 mm or greater was always reconstructed with a nerve graft. Gaps between 4 and 8 mm were repaired under tension or a nerve graft was used (Weber et al., 2000). Chiriac and colleagues stated in their discussion that excessive tension on the nerve repair compromises the quality of clinical outcome. However, we also know that some tension on the suture lines is well tolerated (Sunderland et al., 2004). In fact, the outcomes of the Neurolac™ prospective randomized multicenter study, mentioned above, has shown equal functional outcomes between gaps bridged under tension and reconstructed using a nerve guide.
One might consider collagen nerve guides as an alternative. Moore et al. presented three patients (four collagen nerve conduits) following failed reconstructions using collagen NeuraGen nerve conduits (Moore et al., 2009), and concluded that the indications for reconstruction with the NeuraGen nerve conduit should be restricted to divided distal sensory nerves with short gaps. Furthermore, temporary foreign body sensation in the area of the implant in three, and persistent in one out of 11 patients, was described by Lohmeyer et al. after using collagen NeuraGen nerve guides in distal sensory nerve reconstructions (2007). Finally, Wangensteen published about their results of using collagen NeuraGen nerve guides for upper extremity sensory nerves and published that, in the group of patients in whom 2PD was determined, only 24% showed improvement (Wangensteen and Kalliainen, 2009).
It is difficult to draw conclusions from different kinds of (rat) studies with regard to clinical outcomes. The study from Meek and den Dunnen was performed using porous Neurolac™ nerve guides (Meek and den Dunnen, 2009). Swelling and obstruction of the lumen was observed. We believe this is owing to enlargement of the surface area, in turn leading to more water uptake causing swelling and obstruction. These data were given to the company making these nerve guides and as far as we know there has never been a porous Neurolac™ nerve guide available for clinical use.
We agree that surgeons should be careful about using biomaterials that will leave remnants in situ causing a (secondary) foreign body reaction. Conclusions based on degradation of a component (lactic acid), however, cannot be made so easily. There are different types of Poly Lactide Acid (PLA). Some types of PLA biomaterials may cause remnants of degraded PLA surrounded by a dense capsule. This PLA material can be found within the cytoplasm of macrophages and fibroblasts. Moreover, copolymerization of L-lactide with D-lactide, glycolide, ε-caprolactone (like Neurolac™ nerve guides) and trimethylene carbonate has yielded non-crystallizable materials with a broad spectrum of initial properties and hydrolytic bulk degradation patterns.
Nerve guide implantation, just like implanting any other biomaterial (knee prosthesis), will need good vascularized soft tissue cover. Furthermore, patients undergoing nerve reconstruction using a nerve guide should be informed about protrusion risks of around one in 12. Care should be taken when implanting nerve guides nearby a joint. All nerve guides come with complications, just like any other operation. There is not much literature of large series on reconstruction of large peripheral nerves. Unfavourable outcomes of a clinical study do not necessarily mean or imply that one needs to abandon this technique. In addition, rat and human studies are by no means always comparable.
We do not understand the sentence in Chiriac’s discussion about comparing patients with nerve defects of more or less than 5 mm . Chiriac and colleagues operated on only one patient with a nerve defect of less than 5 mm so valid comparisons cannot be made.
With regard to the nerve guide prices, we received personal reactions on our publication that these price differences seem to differ significantly per country. To our knowledge, Ascension is no longer the distributor of Neurolac™.
Although it is stated that there was no benefit at all after secondary digital nerve reconstruction in the foot, pain (often the main concern of the patient) resolved after repair of the nerve defect using a Neurolac™ nerve guide (Meek et al., 2006).
Finally, we agree with Chiriac and colleagues that needle passage through the Neurolac™ wall is difficult. It is our experience that very thin needles (e.g. 10-0 nylon) break easily. We recently noticed, however, that a thin-walled Neurolac™ nerve guide is available on the market in order to facilitate needle passage.