Longitudinal traumatic peripheral nerve injury recovery: quantitative description, classification and prediction.

Aim: Repair of peripheral nerves is recommended following transection. Systematic evaluation of longitudinal recovery in injury models is needed to improve patient management. Gompertz function provided straightforward interpretation and prediction of recovery outcomes. Materials & methods: Behavioural sciatic function index, measured 3 days post injury, and weekly for 12 weeks following full nerve transection and repair (n = 6) as well as crush injuries (n = 6). Results: Gompertz parametrization provided early classification between types of traumatic peripheral nerve injuries following surgical repair. Results distinguished injury nerves (A: p < 0.01; Ti: p < 0.05; Ic: p < 0.05 and outcome: p < 0.01). Early prognostication of outcomes (crush: 5.5 ± 0.3 and cut/repair: 8 ± 1 weeks) preceded current methods. Conclusion: Our findings identify injury type, state of recovery and early prognostication of outcome.

Noninvasive diffusion MRI to determine the severity of peripheral nerve injury.

OBJECTIVE: Primary repair of peripheral nerves is recommended following transection; however, patient management following repair is challenged by a lack of biomarkers to nerve regeneration. Previous studies have demonstrated that diffusion magnetic resonance imaging (MRI) may provide viable biomarkers of nerve regeneration in injury models; though, these methods have not been systematically evaluated in graded partial transections and repairs. METHODS: Ex vivo diffusion MRI was performed in fixed rat sciatic nerve samples 4 or 12 weeks following partial nerve transection and repair (25% cut = 12, 50% cut = 12 and 75% cut = 11), crush injuries (n = 12), and sham surgeries (n = 9). Behavioral testing and histologic evaluation were performed in the same animals and nerve samples for comparison. RESULTS: Diffusion tractography provided visual characterizations of nerve damage and recovery consistent with the expected degree of injury within each cohort. In addition, quantitative indices from diffusion MRI correlated with both histological and behavioral evaluations, the latter of indicated full recovery for sham and crush nerves and limited recovery in all partially transected/repaired nerves. Nerve recovery between 4 and 12 weeks was statistically significant in partial transections 50% and 75% depth cuts (p = 0.043 and p = 0.022) but not for 25% transections. INTERPRETATION: Our findings suggest that DTI can i) distinguish different degrees of partial nerve transection following surgical repair and ii) map spatially heterogeneous nerve recovery (e.g., due to collateral sprouting) from 4 to 12 weeks in partially transected nerves.

Author Correction: Probabilistic Assessment of Nerve Regeneration with Diffusion MRI in Rat Models of Peripheral Nerve Trauma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Diffusion Magnetic Resonance Imaging Predicts Peripheral Nerve Recovery in a Rat Sciatic Nerve Injury Model.

BACKGROUND: Nerve regeneration after an injury should occur in a timely fashion for function to be restored. Current methods cannot monitor regeneration prior to muscle reinnervation. Diffusion tensor imaging has been previously shown to provide quantitative indices after nerve recovery. The goal of this study was to validate the use of this technology following nerve injury via a series of rat sciatic nerve injury/repair studies. METHODS: Sprague-Dawley rats were prospectively divided by procedure (sham, crush, or cut/repair) and time points (1, 2, 4, and 12 weeks after surgery). At the appropriate time point, each animal was euthanized and the sciatic nerve was harvested and fixed. Data were obtained using a 7-Tesla magnetic resonance imaging system. For validation, findings were compared to behavioral testing (foot fault asymmetry and sciatic function index) and cross-sectional axonal counting of toluidine blue-stained sections examined under light microscopy. RESULTS: Sixty-three rats were divided into three treatment groups (sham, n = 21; crush, n = 23; and cut/repair, n = 19). Fractional anisotropy was able to differentiate between recovery following sham, crush, and cut/repair injuries as early as 2 weeks (p < 0.05), with more accurate differentiation thereafter. More importantly, the difference in anisotropy between distal and proximal regions recognized animals with successful and failed recoveries according to behavioral analysis, especially at 12 weeks. In addition, diffusion tension imaging-based tractography provided a visual representation of nerve continuity in all treatment groups. CONCLUSIONS: Diffuse tensor imaging is an objective and noninvasive tool for monitoring nerve regeneration. Its use could facilitate earlier detection of failed repairs to potentially help improve outcomes.

Probabilistic Assessment of Nerve Regeneration with Diffusion MRI in Rat Models of Peripheral Nerve Trauma.

Nerve regeneration after injury must occur in a timely fashion to restore function. Unfortunately, current methods (e.g., electrophysiology) provide limited information following trauma, resulting in delayed management and suboptimal outcomes. Herein, we evaluated the ability of diffusion MRI to monitor nerve regeneration after injury/repair. Sprague-Dawley rats were divided into three treatment groups (sham = 21, crush = 23, cut/repair = 19) and ex vivo diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) was performed 1-12 weeks post-surgery. Behavioral data showed a distinction between crush and cut/repair nerves at 4 weeks. This was consistent with DTI, which found that thresholds based on the ratio of radial and axial diffusivities (RD/AD = 0.40 ± 0.02) and fractional anisotropy (FA = 0.53 ± 0.01) differentiated crush from cut/repair injuries. By the 12th week, cut/repair nerves whose behavioral data indicated a partial recovery were below the RD/AD threshold (and above the FA threshold), while nerves that did not recover were on the opposite side of each threshold. Additional morphometric analysis indicated that DTI-derived normalized scalar indices report on axon density (RD/AD: r = -0.54, p < 1e-3; FA: r = 0.56, p < 1e-3). Interestingly, higher-order DKI analyses did not improve our ability classify recovery. These findings suggest that DTI may provide promising biomarkers for distinguishing successful/unsuccessful nerve repairs and potentially identify cases that require reoperation.

Endoscopically Guided Laparoscopic Gastrojejunostomy Tube Placement for Patients with Distal Esophageal Stents.

Patients with distal esophageal pathology such as perforation, trachea-esophageal fistulae, and/ or obstructing gastroesophageal junction tumor present a challenging situation in terms of feeding access where an esophageal stent is placed across the gastroesophageal junction. In order to allow simultaneous gastric decompression and post-pyloric feeds without significant reflux up through the stent, a gastrojejunostomy (GJ) tube is a viable option. We hereby describe a hybrid approach to placing these GJ tubes in this cohort of patients using simultaneous laparoscopy, endoscopy, and fluoroscopy with minimal manipulation of the stent itself. We have employed this technique of placing GJ tubes 2-3 days following placement of the esophageal stent in six consecutive patients. All patients tolerated the procedure well without any complications. Endoscopically guided laparoscopic GJ tubes are ideal for bridging patients, with distal esophageal pathology requiring esophageal stents, to oral intake.