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OBJECTIVE: Functional recovery is disappointing after surgical repair of nerves that are injured far from their target organs and/or after delayed repair. In the former case, a nerve transfer that transects a distal nerve fascicle to innervate denervated targets is one strategy to promote nerve regeneration and functional recovery. An alternate strategy tested in this study is to perform an end-to-side neurorrhaphy to "babysit" (protect) the denervated distal nerve stump at the time of nerve repair and reduce the deleterious effect of chronic denervation on nerve regeneration. METHODS: In the hindlimbs of Sprague-Dawley rats, the common peroneal (CP) nerve was transected unilaterally and the distal CP nerve stump inserted through a perineurial window into the intact tibial (TIB) nerve, i.e., CP-TIB end-to-side neurorrhaphy. In the first experiment, TIB nerve motoneurons that had regenerated and/or sprouted axons into the CP nerve within 3 months were stimulated to elicit contractions, and thereafter, identified with retrograde dyes for counting. In the second experiment, the intact TIB nerve was transected and cross-sutured to a 3-month chronically denervated distal CP nerve stump that had either been "protected" by ingrown TIB nerves after CP-TIB neurorrhaphy or remained chronically denervated. Thereafter, the number of retrogradely labeled TIB nerve motoneurons that had regenerated their nerves within 3 months were counted and reinnervated tibialis anterior (TA) muscles weighed. RESULTS: A mean (± SE) of 231 ± 83 TIB nerve motoneurons grew into the end-to-side CP distal nerve stump with corresponding ankle flexion; 32% regenerated their axons and 24% sprouted axons from the intact TIB nerve, eliciting ankle flexor-extensor co-contraction. In the second experiment, after a 3-month period of TIB nerve regeneration, significantly more TIB motoneurons regenerated their axons into "protected" than "unprotected" CP distal nerve stumps within 3 months (mean 332 ± 43.6 vs 235 ± 39.3 motoneurons) with corresponding and significantly higher numbers of regenerated nerve fibers, resulting in significantly better recovery of reinnervated TA muscle weight. CONCLUSIONS: These experiments in rats demonstrated that delayed nerve repair is more effective when the deleterious effects of chronic denervation of the distal nerve stump are reduced by protecting the nerve stump with ingrowing nerve fibers across an end-to-side insertion of the distal nerve stump into a neighboring intact nerve. Such an end-to-side neurorrhaphy may be invaluable as a means of preventing the atrophy of distal nerve stumps and target organs after chronic denervation, which allows for effective reinnervation of the protected distal nerve stumps and target organs over distance and time.

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OBJECTIVE: The aim of this study was to compare sensitivity and specificity between the novel threshold and amplitude criteria for motor evoked potentials (MEPs) monitoring after transcranial electrical stimulation (TES) during surgery for supratentorial lesions in the same patient cohort. METHODS: One hundred twenty-six patients were included. All procedures were performed under general anesthesia. Craniotomies did not expose motor cortex, so that direct mapping was less suitable. After TES, MEPs were recorded bilaterally from abductor pollicis brevis (APB), from orbicularis oris (OO), and/or from tibialis anterior (TA). The percentage increase in the threshold level was assessed and considered significant if it exceeded by more than 20% on the affected side the percentage increase on the unaffected side. Amplitude on the affected side was measured with a stimulus intensity of 150% of the threshold level set for each muscle. RESULTS: Eighteen of 126 patients showed a significant change in the threshold level as well as an amplitude reduction of more than 50% in MEPs recorded from APB, and 15 of the patients had postoperative deterioration of motor function of the arm (temporary in 8 cases and permanent in 7 [true-positive and false-negative results]). Recording from TA was performed in 66 patients; 4 developed postoperative deterioration of motor function of the leg (temporary in 3 cases and permanent in 1), and showed a significant change in the threshold level, and an amplitude reduction of more than 50% occurred in 1 patient. An amplitude reduction of more than 50% occurred in another 10 patients, without a significant change in the threshold level or postoperative deterioration. Recording from OO was performed in 61 patients; 3 developed postoperative deterioration of motor function of facial muscles (temporary in 2 cases and permanent in 1) and had a significant change in the threshold level, and 2 of the patients had an amplitude reduction of more than 50%. Another 6 patients had an amplitude reduction of more than 50% but no significant change in the threshold level or postoperative deterioration.Sensitivity of the threshold criterion was 100% when MEPs were recorded from APB, OO, or TA, and its specificity was 97%, 100%, and 100%, respectively. Sensitivity of the amplitude criterion was 100%, 67%, and 25%, with a specificity of 97%, 90%, and 84%, respectively. CONCLUSIONS: The threshold criterion was comparable to the amplitude criterion with a stimulus intensity set at 150% of the threshold level regarding sensitivity and specificity when recording MEPs from APB, and superior to it when recording from TA or OO.

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OBJECTIVE The sciatic nerve, particularly its peroneal division, is at risk for injury during total hip arthroplasty (THA), especially when a posterior approach is used. The majority of the morbidity results from the loss of peroneal nerve-innervated muscle function. Approximately one-third of patients recover spontaneously. The objectives of this study were to report the outcomes of distal decompression of the peroneal nerve at the fibular tunnel following sciatic nerve injury secondary to THA and to attempt to identify predictors of a positive surgical outcome. METHODS A retrospective study of all patients who underwent peroneal decompression for the indication of sciatic nerve injury following THA at the Mayo Clinic or Washington University School of Medicine in St. Louis was performed. Patients with less than 6 months of postoperative follow-up were excluded. The primary outcome was dorsiflexion strength at latest follow-up. Univariate and multivariate logistic regression analyses were performed to assess the ability of the independent variables to predict a good surgical outcome. RESULTS The total included cohort consisted of 37 patients. The median preoperative dorsiflexion grade at the time of peroneal decompression was 0. Dorsiflexion at latest follow-up was Medical Research Council (MRC) ≥ 3 for 24 (65%) patients. Dorsiflexion recovered to MRC ≥ 4- for 15 (41%) patients. In multivariate logistic regression analysis, motor unit potentials in the tibialis anterior (OR 19.84, 95% CI 2.44-364.05; p = 0.004) and in the peroneus longus (OR 8.68, 95% CI 1.05-135.53; p = 0.04) on preoperative electromyography were significant predictors of a good surgical outcome. CONCLUSIONS After performing peroneal nerve decompression at the fibular tunnel, 65% of the patients in this study recovered dorsiflexion strength of MRC ≥ 3 at latest follow-up, potentially representing a significant improvement over the natural history.

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OBJECTIVE Electrical stimulation of peripheral nerve tissue has been shown to accelerate axonal regeneration. Yet existing methods of applying electrical stimulation to injured peripheral nerves have presented significant barriers to clinical translation. In this study, the authors examined the use of a novel implantable wireless nerve stimulator capable of simultaneously delivering therapeutic electrical stimulation of injured peripheral nerve tissue and providing postoperative serial assessment of functional recovery. METHODS Flexible wireless stimulators were fabricated and implanted into Lewis rats. Thin-film implants were used to deliver brief electrical stimulation (1 hour, 20 Hz) to sciatic nerves after nerve crush or nerve transection-and-repair injuries. RESULTS Electrical stimulation of injured nerves via implanted wireless stimulators significantly improved functional recovery. Brief electrical stimulation was observed to increase the rate of functional recovery after both nerve crush and nerve transection-and-repair injuries. Wireless stimulators successfully facilitated therapeutic stimulation of peripheral nerve tissue and serial assessment of nerve recovery. CONCLUSIONS Implantable wireless stimulators can deliver therapeutic electrical stimulation to injured peripheral nerve tissue. Implantable wireless nerve stimulators might represent a novel means of facilitating therapeutic electrical stimulation in both intraoperative and postoperative settings.

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OBJECTIVE The aim of the present study was to evaluate the usefulness of navigated transcranial magnetic stimulation (nTMS) as a prognostic predictor for upper-extremity motor functional recovery from postsurgical neurological deficits. METHODS Preoperative and postoperative nTMS studies were prospectively applied in 14 patients (mean age 39 ± 12 years) who had intraparenchymal brain neoplasms located within or adjacent to the motor eloquent area in the cerebral hemisphere. Mapping by nTMS was done 3 times, i.e., before surgery, and 1 week and 3 weeks after surgery. To assess the response induced by nTMS, motor evoked potential (nTMS-MEP) was recorded using a surface electromyography electrode attached to the abductor pollicis brevis (APB). The cortical locations that elicited the largest electromyography response by nTMS were defined as hotspots. Hotspots for APB were confirmed as positive responsive sites by direct electrical stimulation (DES) during awake craniotomy. The distances between hotspots and lesions (DHS-L) were measured. Postoperative neurological deficits were assessed by manual muscle test and dynamometer. To validate the prognostic value of nTMS in recovery from upper-extremity paresis, the following were investigated: 1) the correlation between DHS-L and the serial grip strength change, and 2) the correlation between positive nTMS-MEP at 1 week after surgery and the serial grip strength change. RESULTS From the presurgical nTMS study, MEPs from targeted muscles were identified in 13 cases from affected hemispheres. In one case, MEP was not evoked due to a huge tumor. Among 9 cases from which intraoperative DES mapping for hand motor area was available, hotspots for APB identified by nTMS were concordant with DES-positive sites. Compared with the adjacent group (DHS-L < 10 mm, n = 6), the nonadjacent group (DHS-L ≥ 10 mm, n = 7) showed significantly better recovery of grip strength at 3 months after surgery (p < 0.01). There were correlations between DHS-L and recovery of grip strength at 1 week, 3 weeks, and 3 months after surgery (r = 0.74, 0.68, and 0.65, respectively). Postsurgical nTMS was accomplished in 13 patients. In 9 of 13 cases, nTMS-MEP from APB muscle was positive at 1 week after surgery. Excluding the case in which nTMS-MEP was negative from the presurgical nTMS study, recoveries in grip strength were compared between 2 groups, in which nTMS-MEP at 1 week after surgery was positive (n = 9) or negative (n = 3). Significant differences were observed between the 2 groups at 1 week, 3 weeks, and 3 months after surgery (p < 0.01). Positive nTMS-MEP at 1 week after surgery correlated well with the motor recovery at 1 week, 3 weeks, and 3 months after surgery (r = 0.87, 0.88, and 0.77, respectively). CONCLUSIONS Navigated TMS is a useful tool for identifying motor eloquent areas. The results of the present study have demonstrated the predictive value of nTMS in upper-extremity motor function recovery from postsurgical neurological deficits. The longer DHS-L and positive nTMS-MEP at 1 week after surgery have prognostic values of better recovery from postsurgical neurological deficits.

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OBJECTIVE Because of its huge clinical potential, the importance of premotor areas for motor function itself and plastic reshaping due to tumors or ischemic brain lesions has received increased attention. Thus, in this study the authors used navigated transcranial magnetic stimulation (nTMS) to investigate whether tumorous brain lesions induce a change in motor cortex localization in the human brain. METHODS Between 2010 and 2013, nTMS motor mapping was performed in a prospective cohort of 100 patients with brain tumors in or adjacent to the rolandic cortex. Spatial data analysis was performed by normalization of the individual motor maps and creation of overlays according to tumor location. Analysis of motor evoked potential (MEP) latencies was performed regarding mean overall latencies and potentially polysynaptic latencies, defined as latencies longer than 1 SD above the mean value. Hemispheric dominance, lesion location, and motor-function deficits were also considered. RESULTS Graphical analysis showed that motor areas were not restricted to the precentral gyrus. Instead, they spread widely in the anterior-posterior direction. An analysis of MEP latency showed that mean MEP latencies were shortest in the precentral gyrus and longest in the superior and middle frontal gyri. The percentage of latencies longer than 1 SD differed widely across gyri. The dominant hemisphere showed a greater number of longer latencies than the nondominant hemisphere (p < 0.0001). Moreover, tumor location-dependent changes in distribution of polysynaptic latencies were observed (p = 0.0002). Motor-function deficit did not show any statistically significant effect. CONCLUSIONS The distribution of primary and polysynaptic motor areas changes in patients with brain tumors and highly depends on tumor location. Thus, these data should be considered for resection planning.

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Successful management of peripheral nerve trauma relies on accurate localization of the injury and grading of the severity of nerve injury to determine whether surgical intervention is required. Existing techniques, such as electrodiagnostic studies and conventional imaging modalities, provide important information, but are limited by being unable to distinguish severe nerve lesions in continuity that will recover from those that will not. Diffusion tensor imaging (DTI) and tractography of peripheral nerves provide a novel technique to localize and grade nerve injury, by assessing the integrity of the nerve fibers across the site of nerve injury. Diffusion tensor imaging and tractography also hold promise as markers of early nerve regeneration, prior to clinical and electrodiagnostic evidence of recovery. In the present review, the techniques of peripheral nerve DTI and tractography are discussed with respect to peripheral nerve trauma, with illustrative cases demonstrating potential roles of these novel approaches.

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OBJECT: Reports of the accuracy of existing neuromonitoring methods for detecting or preventing medial malpositioning of thoracic pedicle screws have varied widely in their claimed effectiveness. The object of this study was to develop, test, and validate a novel neuromonitoring method for preventing medial malpositioning of pedicle screws in the thoracic spine during surgery. METHODS: This is a prospective, blinded and randomized study using a novel combination of input (4-pulse stimulus trains delivered within the pedicle track) and output (evoked electromyography from leg muscles) to detect pedicle track trajectories that-once implanted with a screw-would cause that screw to breach the pedicle's medial wall and encroach upon the spinal canal. For comparison, the authors also used screw stimulation as an input and evoked electromyogram from intercostal and abdominal muscles as output measures. Intraoperative electrophysiological findings were compared with postoperative CT scans by multiple reviewers blinded to patient identity or intraoperative findings. RESULTS: Data were collected from 71 patients, in whom 802 screws were implanted between the T-1 and L-1 vertebral levels. A total of 32 screws ended up with screw threads encroaching on the spinal canal by at least 2 mm. Pulse-train stimulation within the pedicle track using a ball-tipped probe and electromyography from lower limb muscles correctly predicted all 32 (100%) of these medially malpositioned screws. The combination of pedicle track stimulation and electromyogram response from leg muscles proved to be far more effective in predicting these medially malpositioned screws than was direct screw stimulation and any of the target muscles (intercostal, abdominal, or lower limb muscles) we monitored. Based on receiver operating characteristic analysis, the combination of 10-mA (lower alarm) and 15-mA stimulation intensities proved most effective for detection of pedicle tracks that ultimately gave rise to medially malpositioned screws. Additional results pertaining to the impact of feedback of these test results on surgical decision making are provided in the companion report. CONCLUSIONS: This novel neuromonitoring approach accurately predicts medially malpositioned thoracic screws. The approach could be readily implemented within any surgical program that is already using contemporary neuromonitoring methods that include transcranial stimulation for monitoring motor evoked potentials.

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OBJECT: The authors have reported in Part 1 of this study on a novel neuromonitoring test for the prevention of medial malpositioning of thoracic pedicle screws. In the present paper they examine the impact of providing the results of the test as intraoperative feedback to the surgical team. METHODS: This is the second part of a 2-part report of a prospective, blinded and randomized neuromonitoring study designed to lower the incidence of medially malpositioned thoracic pedicle screws. Details of the neuromonitoring technique and data supporting the alarm criteria used are contained in the companion article (Part 1). For the majority of pedicle screw placements, intraoperative test results were withheld from the study team (that is, the team members were blinded to the test results). However, for a limited number of pedicle sites the authors provided one of 2 forms of testing feedback to the surgical team: 1) "break the blind" feedback, if testing suggested that screw placement would result in direct contact between screw and the dura mater; and 2) "planned" feedback, beginning during the later stages of the study and provided for 50% of pedicle sites. Feedback gave the surgeon the opportunity to adjust the trajectory that the screw would ultimately take within the pedicle. The final screw position relative to the pedicle's medial wall for all sites in which feedback was withheld from the surgical team was compared with the screw position for those sites in which either form of feedback ("break the blind" or "planned") was provided to and acted upon by the surgical team. RESULTS: Of the 820 pedicle tracks tested among the 71 surgical cases included in this study, a total of 684 were operated upon without any form of feedback. Planned feedback was provided for an additional 107 pedicle tracks, of which 15 triggered an intraoperative alarm (evoked electromyogram response in leg muscles to stimulus intensity ≤ 10 mA) leading to a warning to the surgical team of a medially biased pedicle track. Finally, the blind was broken 29 times, in each case when testing revealed a particularly low threshold (≤ 4 mA) for evoked responses in leg muscles when stimulating along the pedicle track with the ball-tipped probe. As detailed in the companion paper to this one, there were 32 screws with threads lying at least 2 mm medial to the pedicle wall. In all 32 instances (100%), either these screws were in the "no feedback" category (n = 29) or they were in a feedback category but the surgeon elected to not revise the pedicle-track trajectory. Two patients returned to the operating room for revision of screw placements because the screws were encroaching upon the central canal; the pedicle tracks for these screws had been in the "no feedback" category. CONCLUSIONS: This is the first blinded and randomized study to prove that implementing a novel neuromonitoring strategy during placement of thoracic pedicle screws can significantly reduce the incidence of clinically relevant thoracic pedicle screw medial malpositioning.

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