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Carmen L. A. M. Vleggeert-Lankamp

Object

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.

Methods

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.

Results

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.

Conclusions

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.

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Giorgos D. Michalopoulos, Karim Rizwan Nathani, and Mohamad Bydon

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Anna B. Lebouille-Veldman, Dylan Spenkelink, Cornelia F. Allaart, and Carmen L. A. Vleggeert-Lankamp

OBJECTIVE

The authors’ objective was to evaluate the association of the Disease Activity Score (DAS) with cervical spine deformity in rheumatoid arthritis (RA) patients during 10-year optimal treatment of systemic disease.

METHODS

The authors evaluated radiological and 10-year follow-up (FU) data of the BeSt (BehandelStrategien) trial. In 272 RA patients, atlantoaxial subluxation (AAS), presence of vertical translocation (VT), and subaxial subluxation (SAS) were evaluated. The associations of these deformities with DAS, self-assessed health (determined with the Health Assessment Questionnaire [HAQ]), and erosions of the hands and feet (Sharp–Van der Heijde score) were studied.

RESULTS

After 10 years of FU, AAS (> 2 mm neutral position) was observed in 62 patients (23%), AAS (≥ 3 mm in flexion) in 24%, AAS (≥ 5 mm in flexion) in 7%, VT did not occur, and SAS was present in 60 patients (22%). In total, 135 patients (50%) were in remission (DAS < 1.6) at 10 years of FU. No association could be established between AAS and DAS. Patients with cervical spine deformity (AAS > 2 mm and/or SAS) at 10 years had a higher HAQ score at 10 years than patients without cervical spine deformity (HAQ scores of 0.65 and 0.51, respectively, p = 0.04; 95% CI –0.29 to 0.00).

CONCLUSIONS

Even though 50% of patients were in remission after 10 years and the BeSt trial was designed to optimize treatment, 40% of patients developed at least mild RA-associated cervical spine deformity and 7% developed significant AAS. This indicates that even in this era of disease-modifying antirheumatic drugs and biologicals, cervical deformity is prevalent among patients with RA and should not be neglected in patient treatment plans and information.

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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

Object

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.

Methods

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.

Results

Type grouping was more abundant after crush injury than after autograft or single-lumen nerve graft repair.

Conclusions

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.

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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

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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)

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Catharina D. Schenck, Sietse E. S. Terpstra, Wouter A. Moojen, Erik van Zwet, Wilco Peul, Mark P. Arts, and Carmen L. A. Vleggeert-Lankamp

OBJECTIVE

Interspinous process distraction devices (IPDs) can be implanted to treat patients with intermittent neurogenic claudication (INC) due to lumbar spinal stenosis. Short-term results provided evidence that the outcomes of IPD implantation were comparable to those of decompressive surgery, although the reoperation rate was higher in patients who received an IPD. This study focuses on the long-term results.

METHODS

Patients with INC and spinal stenosis at 1 or 2 levels randomly underwent either decompression or IPD implantation. Patients were blinded to the allocated treatment. The primary outcome was the Zurich Claudication Questionnaire (ZCQ) score at 5-year follow-up. Repeated measurement analysis was applied to compare outcomes over time.

RESULTS

In total, 159 patients were included and randomly underwent treatment: 80 patients were randomly assigned to undergo IPD implantation, and 79 underwent spinal bony decompression. At 5 years, the success rates in terms of ZCQ score were similar (68% of patients who underwent IPD implantation had a successful recovery vs 56% of those who underwent bony decompression, p = 0.422). The reoperation rate at 2 years after surgery was substantial in the IPD group (29%), but no reoperations were performed thereafter. Long-term visual analog scale score for back pain was lower in the IPD group than the bony decompression group (p = 0.02).

CONCLUSIONS

IPD implantation is a more expensive alternative to decompressive surgery for INC but has comparable functional outcome during follow-up. The risk of reoperation due to absence of recovery is substantial in the first 2 years after IPD implantation, but if surgery is successful this positive effect remains throughout long-term follow-up. The IPD group had less back pain during long-term follow-up, but the clinical relevance of this finding is debatable.

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John W. Gilbert, Brydon Christensen, and Sherri Matheny

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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

Object

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.

Methods

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).

Results

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).

Conclusions

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/).

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Carmen L. A. M. Vleggeert-Lankamp, Jasper Wolfs, Ana Paula Pêgo, Rutgeris van den Berg, Hans Feirabend, and Egbert Lakke

Object

In the present study the authors consider the influence of the porosity of synthetic nerve grafts on peripheral nerve regeneration.

Methods

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.

Results

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.

Conclusions

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.

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Kayoumars Azizpour, Pieter Schutte, Mark P. Arts, Willem Pondaag, Gerrit J. Bouma, Maarten Coppes, Erik van Zwet, Wilco C. Peul, and Carmen L. A. Vleggeert-Lankamp

OBJECTIVE

The most advocated surgical technique to treat symptoms of isthmic spondylolisthesis is decompression with instrumented fusion. A less-invasive classical approach has also been reported, which consists of decompression only. In this study the authors compared the clinical outcomes of decompression only with those of decompression with instrumented fusion in patients with isthmic spondylolisthesis.

METHODS

Eighty-four patients with lumbar radiculopathy or neurogenic claudication secondary to low-grade isthmic spondylolisthesis were randomly assigned to decompression only (n = 43) or decompression with instrumented fusion (n = 41). Primary outcome parameters were scores on the Roland Disability Questionnaire (RDQ), separate visual analog scales (VASs) for back pain and leg pain, and patient report of perceived recovery at 12-week and 2-year follow-ups. The proportion of reoperations was scored as a secondary outcome measure. Repeated measures ANOVA according to the intention-to-treat principle was performed.

RESULTS

Decompression alone did not show superiority in terms of disability scores at 12-week follow-up (p = 0.32, 95% CI −4.02 to 1.34), nor in any other outcome measure. At 2-year follow-up, RDQ disability scores improved more in the fusion group (10.3, 95% CI 3.9–8.2, vs 6.0, 95% CI 8.2–12.4; p = 0.006, 95% CI −7.3 to −1.3). Likewise, back pain decreased more in the fusion group (difference: −18.3 mm, CI −32.1 to −4.4, p = 0.01) on a 100-mm VAS scale, and a higher proportion of patients perceived recovery as showing “good results” (44% vs 74%, p = 0.01). Cumulative probabilities for reoperation were 47% in the decompression and 13% in the fusion group (p < 0.001) at the 2-year follow-up.

CONCLUSIONS

In patients with isthmic spondylolisthesis, decompression with instrumented fusion resulted in comparable short-term results, significantly better long-term outcomes, and fewer reoperations than decompression alone. Decompression with instrumented fusion is a superior surgical technique that should in general be offered as a first treatment option for isthmic spondylolisthesis, but not for degenerative spondylolisthesis, which has a different etiology.