Pain in the Context of Sensory Deafferentation.

Pain that accompanies deafferentation is one of the most mysterious and misunderstood medical conditions. Prevalence rates for the assorted conditions vary considerably but the most reliable estimates are greater than 50% for strokes involving the somatosensory system, brachial plexus avulsions, spinal cord injury, and limb amputation, with controversy surrounding the mechanistic contributions of deafferentation to ensuing neuropathic pain syndromes. Deafferentation pain has also been described for loss of other body parts (e.g., eyes and breasts) and may contribute to between 10% and upwards of 30% of neuropathic symptoms in peripheral neuropathies. There is no pathognomonic test or sign to identify deafferentation pain, and part of the controversy surrounding it stems from the prodigious challenges in differentiating cause and effect. For example, it is unknown whether cortical reorganization causes pain or is a byproduct of pathoanatomical changes accompanying injury, including pain. Similarly, ascertaining whether deafferentation contributes to neuropathic pain, or whether concomitant injury to nerve fibers transmitting pain and touch sensation leads to a deafferentation-like phenotype can be clinically difficult, although a detailed neurologic examination, functional imaging, and psychophysical tests may provide clues. Due in part to the concurrent morbidities, the physical, psychologic, and by extension socioeconomic costs of disorders associated with deafferentation are higher than for other chronic pain conditions. Treatment is symptom-based, with evidence supporting first-line antineuropathic medications such as gabapentinoids and antidepressants. Studies examining noninvasive neuromodulation and virtual reality have yielded mixed results.

Brain plasticity in neonatal brachial plexus palsies: quantification and comparison with adults' brachial plexus injuries.

PURPOSE: To compare two populations of brachial plexus palsies, one neonatal (NBPP) and the other traumatic (NNBPP) who underwent different nerve transfers, using the plasticity grading scale (PGS) for detecting differences in brain plasticity between both groups. METHODS: To be included, all patients had to have undergone a nerve transfer as the unique procedure to recover one lost function. The primary outcome was the PGS score. We also assessed patient compliance to rehabilitation using the rehabilitation quality scale (RQS). Statistical analysis of all variables was performed. A p ≤ 0.050 set as criterion for statistical significance. RESULTS: A total of 153 NNBPP patients and 35 NBPP babies (with 38 nerve transfers) met the inclusion criteria. The mean age at surgery of the NBPP group was 9 months (SD 5.42, range 4 to 23 months). The mean age of NNBPP patients was 22 years (SD 12 years, range 3 to 69). They were operated around sixth months after the trauma. All transfers performed in NBPP patients had a maximum PGS score of 4. This was not the case for the NNBPP population that reached a PGS score of 4 in approximately 20% of the cases. This difference was statistically significant (p < 0.001). The RQS was not significantly different between groups. CONCLUSION: We found that babies with NBPP have a significantly greater capacity for plastic rewiring than adults with NNBPP. The brain in the very young patient can process the changes induced by the peripheral nerve transfer better than in adults.

Femoral intraneural ganglion cyst: the first confirmed case report.

BACKGROUND: Ganglion cysts affecting nerve are rare causes of neuropathy. The formation of intraneural ganglion cysts, once controversial, has recently been clarified. We describe the first modern description of a femoral intraneural ganglion cyst at the hip region. METHODS: A patient presented with a 1 year history of radiating pain, quadriceps weakness and anteromedial leg numbness was found to have a femoral intraneural cyst with a hip joint connection on MRI. RESULTS: Surgical disconnection of the articular branch led to improvement of the neuropathy and resolution of the cyst on postoperative MRI. CONCLUSIONS: The unifying articular (synovial) theory describes the joint origin of intraneural cysts, even when they occur in unusual locations, and their propagation into the parent nerve. Knowledge of this theory can improve outcomes; surgery needs to address the joint origin or capsulolabral defect lest recurrence ensue.

New insights into the evaluation of peripheral nerves lesions: a survival guide for beginners.

PURPOSE: To perform a review of the physical basis of DTI and DCE-MRI applied to Peripheral Nerves (PNs) evaluation with the aim of providing readers the main concepts and tools to acquire these types of sequences for PNs assessment. The potential added value of these advanced techniques for pre-and post-surgical PN assessment is also reviewed in diverse clinical scenarios. Finally, a brief introduction to the promising applications of Artificial Intelligence (AI) for PNs evaluation is presented. METHODS: We review the existing literature and analyze the latest evidence regarding DTI, DCE-MRI and AI for PNs assessment. This review is focused on a practical approach to these advanced sequences providing tips and tricks for implementing them into real clinical practice focused on imaging postprocessing and their current clinical applicability. A summary of the potential applications of AI algorithms for PNs assessment is also included. RESULTS: DTI, successfully used in central nervous system, can also be applied for PNs assessment. DCE-MRI can help evaluate PN's vascularization and integrity of Blood Nerve Barrier beyond the conventional gadolinium-enhanced MRI sequences approach. Both approaches have been tested for PN assessment including pre- and post-surgical evaluation of PNs and tumoral conditions. AI algorithms may help radiologists for PN detection, segmentation and characterization with promising initial results. CONCLUSION: DTI, DCE-MRI are feasible tools for the assessment of PN lesions. This manuscript emphasizes the technical adjustments necessary to acquire and post-process these images. AI algorithms can also be considered as an alternative and promising choice for PN evaluation with promising results.

Nerve autofluorescence under near-ultraviolet light: cutting-edge technology for intra-operative neural tissue visualization in 17 patients.

BACKGROUND: Nerve visualization and the identification of other neural tissues during surgery is crucial for numerous reasons, including the prevention of iatrogenic nerve and neural structure injury and facilitation of nerve repair. However, current methods of intra-operative nerve detection are generally expensive, unproven, and/or technically challenging. Recently, we have documented, in both in vivo animal models and ex vivo human tissue, that nerves autofluorescence when viewed in near-ultraviolet light (NUV). In this paper, we describe our use of nerve autofluorescence to facilitate the visualization of nerves and other neural tissues intra-operatively in 17 patients undergoing a range of surgical procedures. METHODS: Employing the same prototype axon imaging system previously documented to markedly enhance nerve visualization in both in vivo animal and ex vivo human models, surgical fields were observed in 17 patients under both white and NUV light during parotid tumor resection (n = 3), thyroid tumor resection (n = 7), and surgery for peripheral nerve and spinal tumors and injury (n = 7). RESULTS: In all 17 patients, the intra-operative use of the imaging system both was feasible and markedly enhanced the localization of all neural tissues throughout their course within the surgical field. All 17 procedures were successful and devoid of any peri-operative complications or post-operative neurological deficits. CONCLUSIONS: Intra-operatively visualizing auto-fluorescent peripheral nerves and other neural tissues under NUV light is feasible in human patients across a range of clinical scenarios and appears to appreciably enhance nerve and other neural tissue visualization. Controlled studies to explore this technology further are needed.

State of the Art and Advances in Peripheral Nerve Surgery.

This review is intended to describe and actualize the basic knowledge of the three basic entities that affect the peripheral nerve system and can be treated by surgery: nerve trauma, chronic nerve compressions, and tumors.Regarding trauma, emphasis is given on the timing of surgery, given the fact that the moment in which the surgery is performed and the employed microsurgical reconstruction technique are the most important factors in the final result. Open lesions with associated nerve injury should be managed with an early exploration carried out before 7 days. Closed injuries are usually deferred, with few exceptions, from 3 to 6 months after the trauma.In turn, chronic compressions require an appropriate clinical, neurophysiological, and imaging diagnosis. Isolated sensory symptoms can be treated actively though without surgery: motor signs like atrophy should be regarded as a sign for immediate surgery, as a deferred treatment might cause an irreversible nerve and muscular damage. Endoscopic approaches are a valuable tool for treatment in selected neuropathies.Finally, nerve tumors demand a thorough preoperative evaluation, as benign tumors are treated in a very different way when compared to malignant lesions. Benign tumors can usually be safely and completely resected without sacrificing the nerve of origin. When malignancy is confirmed, extensive resection to optimize patient survival is the main objective, potentially at the expense of neurological function. This may then be followed by adjuvant radiation and/or chemotherapy, depending on the nature of the tumor and the completeness of resection attained. The role of nerve biopsy remains controversial, and several modern diagnostic techniques might be helpful.

Use of ultrasound and targeted physiotherapy to manage nerve sutures placed under joint flexion: a case series.

BACKGROUND: Joint flexion to diminish the gap and avoid nerve grafts fell into disuse for decades, but recently attention for using this technique was regained. We report a case series of nerve suture under joint flexion, ultrasound monitoring, and physiotherapy. Our main objective was to determine how effective this multimodality treatment is. METHODS: A retrospective review of 8 patients treated with direct repair with joint flexion was done. Depending on the affected nerve, either the knee or the elbow was flexed intraoperatively to determine if direct suturing was possible. After surgery, the limb was held immobilized. Through serial ultrasounds and a physiotherapy program, the limb was fully extended. If a nerve repair rupture was observed, the patient was re-operated and grafts were used. RESULTS: Of the eight nerve sutures analyzed, four sustained a nerve rupture revealed by US at an early stage, while four did not show any sign of dehiscence. In the patients in whom the nerve suture was preserved, an early and very good response was observed. Ultrasound was 100% accurate at identifying nerve suture preservation. Early detection of nerve failure permitted early re-do surgery using grafts without flexion, ultimately determining good final results. CONCLUSIONS: We observed a high rate of dehiscence in our group of patients treated with direct repair and joint flexion. We believe this was due to an incorrect use of the immobilization device, excessive movement, or a broken device. In opposition to this, we observed that applying direct nerve sutures and joint flexion offers unusually good and fast results. If this technique is employed, it is mandatory to closely monitor suture status with US, together with physiotherapy providing progressive, US-guided extension of the flexed joint. If nerve rupture occurs, the close monitoring dictated by this protocol should ensure the timely application of a successful graft repair.

Nerve spectroscopy: understanding peripheral nerve autofluorescence through photodynamics.

BACKGROUND: Being able to accurately identify sensory and motor nerves is crucial during surgical procedures to prevent nerve injury. We aimed to (1) evaluate the feasibility of performing peripheral human nerve visualization utilizing nerves' own autofluorescence in an ex-vivo model; (2) compare the effect of three different nerve fiber fixation methods on the intensity of fluorescence, indicated as the intensity ratio; and (3) similarly compare three different excitation ranges. METHODS: Samples from various human peripheral nerves were selected postoperatively. Nerve fibers were divided into three groups: Group A nerve fibers were washed with a physiologic solution; Group B nerve fibers were fixated with formaldehyde for 6 h first, and then washed with a physiologic solution; Group C nerve fibers were fixated with formaldehyde for six hours, but not washed afterwards. An Olympus IX83 inverted microscope was used for close-up image evaluation. Nerve fibers were exposed to white-light wavelength spectrums for a specific time frame prior to visualization under three different filters-Filter 1-LF405-B-OMF Semrock; Filter 2-U-MGFP; Filter 3-U-MRFPHQ Olympus, with excitation ranges of 390-440, 460-480, and 535-555, respectively. The fluorescence intensity of all images was subsequently analyzed using Image-J Software, and results compared by analysis of variance (ANOVA). RESULTS: The intensity ratios observed with Filter 1 failed to distinguish the different nerve fiber groups (p = 0.39). Conversely, the intensity ratios seen under Filters 2 and 3 varied significantly between the three nerve-fiber groups (p = 0.021, p = 0.030, respectively). The overall intensity of measurements was greater with Filter 1 than Filter 3 (p < 0.05); however, all nerves were well visualized by all filters. CONCLUSION: The current results on ex vivo peripheral nerve fiber autofluorescence suggest that peripheral nerve fiber autofluorescence intensity does not greatly depend upon the excitation wavelength or fixation methods used in an ex vivo setting. Implications for future nerve-sparing surgery are discussed.

A new, low-cost device to treat depressed "ping-pong" fractures non-surgically: technical note.

OBJECTIVE: The aim of this paper is to describe a low-cost and readily accessed Manual Aspiration Reduction System (MARS) for use treating neonatal ping-pong fractures. METHODS: The MARS is composed of a pediatric anesthesia mask, part of a macro dripper, a 3-way stopcock, and two 60-ml syringes. Prior to its use in our patient, the system was tested on five adult volunteers to maximum negative pressure, and none reported pain during the procedure or experienced any other complication. CLINICAL CASE: A 15-day-old premature girl presented with a congenital ping-pong fracture. Her skull X-ray revealed a right parietal fracture. Neurological examination and transfontanellar ultrasound were normal. Treatment using the MARS was performed at the patient's bedside without sedation or anesthesia. The patient was monitored by the neonatology team throughout. RESULTS: Skull radiography revealed reduction of the fracture after the procedure performed with the MARS. The transfontanellar ultrasound and follow-up neurological examination were normal. The patient progressed favorably and was discharged from our service after 24 h. CONCLUSIONS: Due to its components, the MARS is a low-cost and readily accessed system. In this case, it permitted satisfactory reduction of a ping-pong parietal fracture. This system should greatly simplify the treatment of such fractures.

Neuropathic inguinal pain due to nerve injury after a laparoscopic appendectomy: first pediatric case described in the literature.

OBJECTIVE: To describe the first pediatric case in the literature of neuropathic inguinal pain secondary to iatrogenic nerve injury that occurred during a laparoscopic appendectomy, detailing clinical and morphological findings before and after surgery. The literature on adult patients is reviewed and pathophysiological, therapeutic, and prognostic factors are discussed. CLINICAL PRESENTATION: A 14-year-old female patient presented with a history of a laparoscopic appendectomy 3 years previously. Three months post-operatively, she developed progressively worsening neuropathic inguinal pain refractory to neuromodulators and several nerve blocks. Given her deterioration, poor response to conservative therapy, and clearly meeting the criteria for chronic post-operative inguinal pain (CPIP), surgical management was undertaken. RESULTS: Open surgery was performed through the previous incision, during which injury to a branch of the iliohypogastric nerve (IH) was confirmed. Neurolysis of the affected branch was performed, after which the patient experienced significant pain relief, resolution of allodynia, and reversal of skin hyperpigmentation. After discharge, analgesic therapy was gradually withdrawn and, ultimately, discontinued altogether. CONCLUSIONS: Understanding the neuroanatomy of the inguinal region is an indispensable requirement for all surgeons operating in this region, to avoid complications including CPIP and optimize patient outcomes. Surgical management of CPIP can be effective for controlling severe pain in patients in whom conservative management has failed. Studies are needed in the pediatric population to identify specific characteristics of this entity in youth.

Differences in strength fatigue when using different donors in traumatic brachial plexus injuries.

BACKGROUND: The purpose of this study was to assess the results of elbow flexion strength fatigue, rather than the maximal power of strength, after brachial plexus re-innervation with phrenic and spinal accessory nerves. We designed a simple but specific test to study whether statistical differences were observed among those two donor nerves. METHOD: We retrospectively reviewed patients with severe brachial plexus palsy for which either phrenic nerve (PN) or spinal accessory nerve (SAN) to musculocutaneous nerve (MCN) transfer was performed. A dynamometer was used to determine the maximal contraction strength. One and two kilograms circular weights were utilized to measure isometrically the duration of submaximal and near-maximal contraction time. Statistical analysis was performed between the two groups. RESULTS: Twenty-eight patients were included: 21 with a PN transfer while 7 with a SAN transfer for elbow flexion. The mean time from trauma to surgery was 7.1 months for spinal accessory nerve versus 5.2 for phrenic nerve, and the mean follow-up was 57.7 and 38.6 months, respectively. Statistical analysis showed a quicker fatigue for the PN, such that patients with the SAN transfer could hold weights of 1 kg and 2 kg for a mean of 91.0 and 61.6 s, respectively, while patients with transfer of the phrenic nerve could hold 1 kg and 2 kg weights for just a mean of 41.7 and 19.6 s, respectively. Both differences were statistically significant (at p = 0.006 and 0.011, respectively). Upon correlation analysis, endurances at 1 kg and 2 kg were strongly correlated, with r = 0.85 (p < 0.001). CONCLUSIONS: Our results suggest that phrenic to musculocutaneous nerve transfer showed an increased muscular fatigue when compared with spinal accessory nerve to musculocutaneous transfer. Further studies designed to analyze this relation should be performed to increase our knowledge about strength endurance/fatigue and muscle re-innervation.

In Vivo Corneal Confocal Microscopy: Pre- and Post-operative Evaluation in a Case of Corneal Neurotization.

In this report, we analyse the pre- and post-operative corneal changes observed using in vivo confocal corneal microscopy in a patient with neurotrophic keratitis submitted to a corneal reinnervation surgical procedure. We describe favourable trophic changes observed at different levels of the patient's cornea, particularly in the sub-basal nerve plexus; complete absence of these neurological structures was observed before surgery, but appeared largely restored six months thereafter.

Functional MR Neurography in Evaluation of Peripheral Nerve Trauma and Postsurgical Assessment.

Evaluation of traumatic peripheral nerve injuries has classically been based on clinical and electrophysiologic criteria. US and MRI have been widely used for morphologic assessment of nerve injury sites and concomitant lesions. In the past few years, morphologic MR neurography has significantly increased its clinical applications on the basis of three-dimensional or two-dimensional images with and without fat-suppression techniques. However, these sequences have a major drawback: absence of pathophysiologic information about functional integrity or axonal flow of peripheral nerves. In this scenario, functional MRI techniques such as diffusion-weighted imaging (DWI) or diffusion tensor imaging (DTI) can be used as a complementary tool in initial evaluation of peripheral nerve trauma or in assessment of trauma undergoing surgical repair. These approaches provide not only morphologic but also functional information about extent and degree of nerve impairment. Functional MR neurography can also be applied to selection, planning, and monitoring of surgical procedures that can be performed after traumatic peripheral nerve injuries, such as neurorrhaphy, nerve graft, or neurolysis, as it provides surgeons with valuable information about the functional status of the nerves involved and axonal flow integrity. The physical basis of DWI and DTI and the technical adjustments required for their appropriate performance for peripheral nerve evaluation are reviewed. Also, the clinical value of DWI and DTI in assessment of peripheral nerve trauma is discussed, enhancing their potential impact on selection, planning, and monitoring of surgical procedures employed for peripheral nerve repair. Online supplemental material is available for this article. ©RSNA, 2019.

Peripheral nerve injuries in the pediatric population: a review of the literature. Part III: peripheral nerve tumors in children.

INTRODUCTION: Peripheral nerve tumors type, inciedence and treatment in the pediatric population should be analyzed. METHODS: We have performed an extense literature review of this subject. RESULTS: incidence and distribution are similar to those observed in adults. The most common peripheral nerve tumors in children are neurofibromas and schwannomas. Malignant peripheral nerve sheath tumors are also observed, specially associated with genetic syndromes, like neurofibromatosis and Carney complex. CONCLUSION: In this review, peripheral nerve tumors have been divided into three categories to aid with understanding: reactive and hyperplastic lesions, benign tumors, and malignant tumors. The most frequent lesions have been described.

Peripheral nerve injuries in the pediatric population: a review of the literature. Part II: entrapment neuropathies.

INTRODUCTION: Entrapment neuropathies are infrequent in children, and therefore remain unrecognized. The incidence of radial, median, and cubital mononeuropathies are all similar. Despite the rarity of such cases, extensive, albeit scattered, literature has accumulated concerning entrapment neuropathies in children. OBJECTIVE: To the literature concerning entrapment neuropathies in children. METHODS: A systematic review of the existing literature has been made. RESULTS: The management of chronic pediatric pain is very important in such patients to prevent youths from experiencing prolonged absences from school, sports, or other productive activities, and limit the psychological burden of chronic disease. Nonsurgical treatment of both cubital and carpal tunnel syndromes has been disappointing in pediatric patients, with only limited success; and, to date, there is no clear explanation for the outcome differences generated by nonsurgical management between adults and youths. Simple decompression of the ulnar nerve at the elbow also has much higher rates of failure in children than in adults. CONCLUSIONS: The presence of an entrapment neuropathy (specially carpal tunnel syndrome) in a pediatric-age patient should alert medical care providers to the potential of some underlying genetic condition or syndrome.

Peripheral nerve injuries in the pediatric population: a review of the literature. Part I: traumatic nerve injuries.

OBJECTIVE: This article reviews the clinical results that can be obtained after repair of a traumatic peripheral nerve injury in the pediatric population. METHODS: A systematic review of the published literature has been made. RESULTS: Functional outcome after major nerve injuries is sometimes disappointing in adults. However, children have been reported to experience much better functional results after nerve repair than adults. Moreover, recovery generally is faster in children. The superior capacity of children's central nervous system to adapt to external or internal environmental changes (neural plasticity) and the shorter recovery distance from the axon repair site to the target muscle are claimed to be crucial determinants of their favorable outcomes. Moreover, even in the pediatric population, it has been demonstrated that functional results are better the younger the patient is, including better clinical results in those injured in early childhood (< 6 years old) than in those injured in adolescence. Other favorable prognostic factors include the type of nerve injury (with complete transections doing less well than crush injuries) and the timing of surgery (with better outcomes after early repairs). CONCLUSIONS: All efforts should be done to repair in a timely and adequate fashion traumatic peripheral nerve injuries in children, as the results are good.

Treatment of neuropathic pain after peripheral nerve and brachial plexus traumatic injury.

Peripheral nerve and brachial plexus injuries typically cause severe impairment in the affected limb. The incidence of neuropathic pain is high, reaching up to 95% of cases, especially if cervical root avulsion has occurred. Neuropathic pain results from damage to the somatosensory system, and its progression towards chronicity depends upon disruptions affecting both the peripheral and central nervous system. Managing these painful conditions is complex and must be accomplished by a multidisciplinary team, starting with first-line pharmacological therapies like tricyclic antidepressants and calcium channel ligands, combined physical and occupational therapy, transcutaneous electrical stimulation and psychological support. For patients refractory to the initial measures, several neurosurgical options are available, including nerve decompression or reconstruction and ablative/modulatory procedures.

Intraneural perineuriomas: diagnostic value of magnetic resonance neurography.

Intraneural perineurioma (IP) is an under-recognized hypertrophic peripheral nerve tumor. It affects young patients involving frequently the sciatic nerve and its branches and presents with a progressive, painless and predominantly motor deficit. Magnetic resonance neurography (MRN) is a useful tool to localize the lesion, evaluate its extension, and discriminate between different etiologies. We reviewed the clinical records of 11 patients with pathologically confirm IP. Eight patients were males with mean age 19 years. Initial complains were unilateral steppage (seven patients), bilateral steppage (one patient), unilateral gastrocnemius wasting (one patient), unilateral thigh atrophy (one patient), and unilateral hand weakness (one patient). Nine patients had mild painless sensory loss. Examinations revealed involvement of sciatic nerve extending into the peroneal nerve (eight patients), posterior tibial nerve (one patient), radial nerve (one patient), and femoral nerve (one patient). MRN revealed enlargement of the affected nerve isointense on T1-weighted, hyperintense on T2 fat-saturated images, and with avid enhancement on post-contrast imaging. In all patients, a nerve biopsy confirmed the diagnosis. MRN allows early and non-invasive identification of this tumor and is a key tool providing localization and differential diagnosis in patients with slowly progressive focal neuropathies.

Use of ultrasound and targeted physiotherapy in the management of a nerve suture performed under joint flexion.

BACKGROUND: In 1915, when Delorme described three general requirements for successful nerve repair-(1) resecting scar until a healthy bed is secured, (2) excising damaged nerve until healthy stumps are reached, and (3) placing tension-free sutures, either by adequately mobilizing adjacent joints or nerve grafting-his work was heavily criticized. One century later, history has vindicated all but one of these claims. Flexing adjacent joints to avoid nerve grafts remains controversial, though this practice has increased in recent years. METHODS: An 11-year-old male suffered a penetrating domestic accident that resulted in complete foot drop. At surgery, a 6-cm gap was treated with direct nerve sutures, for which the knee was maintained in 60° flexion in a cast. To avoid damage to the nerve sutures, ultrasound and an intense, though cautious physiotherapy program were employed to guide the progression of knee extension. RESULTS: The patient started to show clear signs of peroneal motor function recovery within 3 months of surgical repair, and almost complete recovery by 4 months postoperatively. CONCLUSIONS: Using physiotherapy and ultrasound might validate the classic joint-flexion technique in select patients with lower-limb nerve injuries.