Carmen L. A. M. Vleggeert-Lankamp
A number of evaluation methods that are currently used to compare peripheral nerve regeneration with alternative repair methods and to judge the outcome of a new paradigm were hypothesized to lack resolving power. This would too often lead to the conclusion that the outcome of a new paradigm could not be discerned from the outcome of the current gold standard, the autograft. As a consequence, the new paradigm would incorrectly be judged as successful.
An overview of the methods that were used to evaluate peripheral nerve regeneration after grafting of the rat sciatic nerve was prepared. All articles that were published between January 1975 and December 2004 and concerned grafting of the rat sciatic nerve (minimum graft length 5 mm) and in which the experimental method was compared with an untreated or another grafted nerve were included. The author scored the presence of statistically significant differences between paradigms.
Evaluation of nerve fiber count, nerve fiber density, N-ratio, nerve histological success ratio, compound muscle action potential, muscle weight, and muscle tetanic force are methods that were demonstrated to have resolving power.
A number of evaluation methods are not suitable to demonstrate a significant difference between experimental paradigms in peripheral nerve regeneration. It is preferable to apply a combination of evaluation methods with resolving power to evaluate nerve regeneration properly.
Abdelilah el Barzouhi, Carmen L. A. M. Vleggeert-Lankamp, Geert J. Lycklama à Nijeholt, Bas F. Van der Kallen, Wilbert B. van den Hout, Bart W. Koes and Wilco C. Peul
In a randomized controlled trial comparing surgery and prolonged conservative treatment for sciatica of 6–12 weeks' duration, more than one-third of patients assigned to conservative treatment underwent surgery. The objective of the present study was to evaluate whether MRI at baseline could have predicted this delayed surgery.
Independently evaluated qualitative and quantitative MRI findings were compared between those patients who did and those who did not undergo surgery during follow-up in the conservative care group. In addition, area under the receiver operating characteristic (ROC) curve analysis was used to assess how well MRI parameters discriminated between those who did and those who did not undergo delayed surgery (0.5–0.7 poor discrimination, ≥ 0.7 acceptable discrimination).
Of 142 patients assigned to receive prolonged conservative care, 55 patients (39%) received delayed surgery. Of the 55 surgically treated patients, 71% had definite nerve root compression at baseline compared with 72% of conservatively treated patients (p = 0.76). Large disc herniations (size > 50% of spinal canal) were nearly equally distributed between those who did and those who did not undergo surgery (25% vs 21%, p = 0.65). The size of the dural sac was smaller in the patients who underwent surgery (101.2 vs 122.9 mm2, p = 0.01). However, the size of the dural sac discriminated poorly between those who did and those who did not undergo delayed surgery (area under ROC curve, 0.62).
In patients who suffered from sciatica of 6–12 weeks' duration, MRI at baseline did not distinguish between patients who did and those who did not undergo delayed surgery. Clinical trial registration no.: ISRCTN26872154 (http://www.controlled-trials.com/ISRCTN/).
M. Sarah S. Bovenberg, M. Hannah Degeling, Godard C. W. de Ruiter, Hans K. P. Feirabend, Egbert A. J. F. Lakke and Carmen L. A. M. Vleggeert-Lankamp
Accuracy of reinnervation is an important factor that determines outcome after nerve injury and repair. Type grouping—the clustering of muscle fibers of the same type after reinnervation—can be used to investigate the accuracy of reinnervation. In this study, the degree of type grouping after crush injury in rats was compared with the clustering of muscle fibers after autografting or single-lumen nerve grafting.
Twelve weeks after sciatic nerve crush injury in rats, clustering of Type I muscle fibers was analyzed in the target muscle with adenosine 5′-triphosphatase staining. In addition, the number of regenerated axons was determined in the nerve distal to the crush injury. Results were compared with that of the authors' previous study.
Type grouping was more abundant after crush injury than after autograft or single-lumen nerve graft repair.
Crush injury leads to more clustered innervation of muscle fibers, probably because the Schwann cell basal lamina tubes are not interrupted as they are in autograft or artificial nerve graft repair. This finding adds to understanding the processes playing a role in nerve regeneration.
Carmen L. A. M. Vleggeert-Lankamp, Jasper Wolfs, Ana Paula Pêgo, Rutgeris van den Berg, Hans Feirabend and Egbert Lakke
In the present study the authors consider the influence of the porosity of synthetic nerve grafts on peripheral nerve regeneration.
Microporous (1–13 μm) and nonporous nerve grafts made of a copolymer of trimethylene carbonate and ε-caprolactone were tested in an animal model. Twelve weeks after surgery, nerve and muscle morphological and electrophysiological results of regenerated nerves that had grown through the synthetic nerve grafts were compared with autografted and untreated (control) sciatic nerves. Based on the observed changes in the number and diameter of the nerve fibers, the predicted values of the electrophysiological parameters were calculated.
The values of the morphometric parameters of the peroneal nerves and the gastrocnemius and anterior tibial muscles were similar if not equal in the rats receiving synthetic nerve grafts. The refractory periods, however, were shorter in porous compared with nonporous grafted nerves, and thus were closer to control values.
A shorter refractory period enables the axon to follow the firing frequency of the neuron more effectively and allows a more adequate target organ stimulation. Therefore, porous are preferred over nonporous nerve grafts.
Abdelilah el Barzouhi, Annemieke J. H. Verwoerd, Wilco C. Peul, Arianne P. Verhagen, Geert J. Lycklama à Nijeholt, Bas F. Van der Kallen, Bart W. Koes, Carmen L. A. M. Vleggeert-Lankamp and For the Leiden–The Hague Spine Intervention Prognostic Study Group
This study aimed to determine the prognostic value of MRI variables to predict outcome in patients with herniated disc–related sciatica, and whether MRI could facilitate the decision making between early surgery and prolonged conservative care in these patients.
A prospective observational evaluation of patients enrolled in a randomized trial with 1-year follow-up was completed. A total of 283 patients with sciatica who had a radiologically confirmed disc herniation were randomized either to surgery or to prolonged conservative care with surgery if needed. Outcome measures were recovery and leg pain severity. Recovery was registered on a 7-point Likert scale. Complete/near complete recovery was considered a satisfactory outcome. Leg pain severity was measured on a 0- to 100-mm visual analog scale. Multiple MRI characteristics of the degenerated disc herniation were independently scored by 3 spine experts. Cox models were used to study the influence of MRI variables on rate of recovery, and linear mixed models were used to determine the predictive value of MRI variables for leg pain severity during follow-up. The interaction of each MRI predictor with treatment allocation was tested. There were no study-specific conflicts of interest.
Baseline MRI variables associated with less leg pain severity were the reader's assessment of presence of nerve root compression (p < 0.001), and assessment of extrusion compared with protrusion of the disc herniation (p = 0.006). Both variables tended to be associated, but not significantly, with satisfactory outcome during follow-up (HR 1.45, 95% CI 0.93–2.24, and HR 1.24, 95% CI 0.96–1.61, respectively). The size of disc herniation at baseline was not associated with outcome. There was no significant change in the effects between treatment groups.
MRI assessment of the presence of nerve root compression and extrusion of a herniated disc at baseline was associated with less leg pain during 1-year follow-up, irrespective of a surgical or conservative treatment. MRI findings seem not to be helpful in determining which patients might fare better with early surgery compared with a strategy of prolonged conservative care.
Clinical trial registration no.: ISRCTN26872154 (controlled-trials.com)
Chao-Hung Kuo, Peng-Yuan Chang, Jau-Ching Wu, Wen-Cheng Huang, Tsung-Hsi Tu and Henrich Cheng