Core outcomes in nerve surgery: development of a core outcome set for brachial plexus and upper extremity nerve injuries.

OBJECTIVE: When considering traumatic brachial plexus and upper extremity nerve injuries, iatrogenic nerve injuries, and nontraumatic nerve injuries, brachial plexus and upper extremity nerve injuries are commonly encountered in clinical practice. Despite this, data synthesis and comparison of available studies are difficult. This is at least in part due to the lack of standardization in reporting and a lack of a core outcome set (COS). Thus, there is a need for a COS for adult brachial plexus and upper extremity nerve injuries (COS-BPUE). The objective of this study was to develop a COS-BPUE using a modified Delphi approach. METHODS: A 5-stage approach was used to develop the COS-BPUE: 1) consortium development, 2) literature review to identify potential outcome measures, 3) Delphi survey to develop consensus on outcomes for inclusion, 4) Delphi survey to develop definitions, and 5) consensus meeting to finalize the COS and definitions. The study followed the Core Outcome Set-STAndards for Development (COS-STAD) recommendations. RESULTS: The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 23 participants, all neurological surgeons, representing 13 countries. The final COS-BPUE consisted of 36 data points/outcomes covering demographic, diagnostic, patient-reported outcome, motor/sensory outcome, and complication domains. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 24 months, with the consensus optimal time points for assessment being preoperatively and 3, 6, 12, and 24 months postoperatively. CONCLUSIONS: The COINS Consortium developed a consensus COS and provided definitions, methods of implementation, and time points for assessment. The COS-BPUE should serve as a minimum set of data that should be collected in all future neurosurgical studies on adult brachial plexus and upper extremity nerve injuries. Incorporation of this COS should help improve consistency in reporting, data synthesis, and comparability, and should minimize outcome reporting bias.

Thoracic Outlet Syndrome Part II: Consensus on the Management of Neurogenic Thoracic Outlet Syndrome by the European Association of Neurosurgical Societies' Section of Peripheral Nerve Surgery.

BACKGROUND: In the first part of this report, the European Association of Neurosurgical Societies' section of peripheral nerve surgery presented a systematic literature review and consensus statements on anatomy, classification, and diagnosis of thoracic outlet syndrome (TOS) along with a subclassification system of neurogenic TOS (nTOS). Because of the lack of level 1 evidence, especially regarding the management of nTOS, we now add a consensus statement on nTOS treatment among experienced neurosurgeons. OBJECTIVE: To document consensus and controversy on nTOS management, with emphasis on timing and types of surgical and nonsurgical nTOS treatment, and to support patient counseling and clinical decision-making within the neurosurgical community. METHODS: The literature available on PubMed/MEDLINE was systematically searched on February 13, 2021, and yielded 2853 results. Screening and classification of abstracts was performed. In an online meeting that was held on December 16, 2021, 14 recommendations on nTOS management were developed and refined in a group process according to the Delphi consensus method. RESULTS: Five RCTs reported on management strategies in nTOS. Three prospective observational studies present outcomes after therapeutic interventions. Fourteen statements on nonsurgical nTOS treatment, timing, and type of surgical therapy were developed. Within our expert group, the agreement rate was high with a mean of 97.8% (± 0.04) for each statement, ranging between 86.7% and 100%. CONCLUSION: Our work may help to improve clinical decision-making among the neurosurgical community and may guide nonspecialized or inexperienced neurosurgeons with initial patient management before patient referral to a specialized center.

Thoracic Outlet Syndrome Part I: Systematic Review of the Literature and Consensus on Anatomy, Diagnosis, and Classification of Thoracic Outlet Syndrome by the European Association of Neurosurgical Societies' Section of Peripheral Nerve Surgery.

BACKGROUND: Although numerous articles have been published not only on the classification of thoracic outlet syndrome (TOS) but also on diagnostic standards, timing, and type of surgical intervention, there still remains some controversy because of the lack of level 1 evidence. So far, attempts to generate uniform reporting standards have not yielded conclusive results. OBJECTIVE: To systematically review the body of evidence and reach a consensus among neurosurgeons experienced in TOS regarding anatomy, diagnosis, and classification. METHODS: A systematic literature search on PubMed/MEDLINE was performed on February 13, 2021, yielding 2853 results. Abstracts were screened and classified. Recommendations were developed in a meeting held online on February 10, 2021, and refined according to the Delphi consensus method. RESULTS: Six randomized controlled trials (on surgical, conservative, and injection therapies), 4 "guideline" articles (on imaging and reporting standards), 5 observational studies (on diagnostics, hierarchic designs of physiotherapy vs surgery, and quality of life outcomes), and 6 meta-analyses were identified. The European Association of Neurosurgical Societies' section of peripheral nerve surgery established 18 statements regarding anatomy, diagnosis, and classification of TOS with agreement levels of 98.4 % (±3.0). CONCLUSION: Because of the lack of level 1 evidence, consensus statements on anatomy, diagnosis, and classification of TOS from experts of the section of peripheral nerve surgery of the European Association of Neurosurgical Societies were developed with the Delphi method. Further work on reporting standards, prospective data collections, therapy, and long-term outcome is necessary.

Neurofibromin Deficiency and Extracellular Matrix Cooperate to Increase Transforming Potential through FAK-Dependent Signaling.

Plexiform neurofibromas (Pnfs) are benign peripheral nerve sheath tumors that are major features of the human genetic syndrome, neurofibromatosis type 1 (NF1). Pnfs are derived from Schwann cells (SCs) undergoing loss of heterozygosity (LOH) at the NF1 locus in an NF1+/- milieu and thus are variably lacking in the key Ras-controlling protein, neurofibromin (Nfn). As these SCs are embedded in a dense desmoplastic milieu of stromal cells and abnormal extracellular matrix (ECM), cell-cell cooperativity (CCC) and the molecular microenvironment play essential roles in Pnf progression towards a malignant peripheral nerve sheath tumor (MPNST). The complexity of Pnf biology makes treatment challenging. The only approved drug, the MEK inhibitor Selumetinib, displays a variable and partial therapeutic response. Here, we explored ECM contributions to the growth of cells lacking Nfn. In a 3D in vitro culture, NF1 loss sensitizes cells to signals from a Pnf-mimicking ECM through focal adhesion kinase (FAK) hyperactivation. This hyperactivation correlated with phosphorylation of the downstream effectors, Src, ERK, and AKT, and with colony formation. Expression of the GAP-related domain of Nfn only partially decreased activation of this signaling pathway and only slowed down 3D colony growth of cells lacking Nfn. However, combinatorial treatment with both the FAK inhibitor Defactinib (VS-6063) and Selumetinib (AZD6244) fully suppressed colony growth. These observations pave the way for a new combined therapeutic strategy simultaneously interfering with both intracellular signals and the interplay between the various tumor cells and the ECM.

Peripheral nerve tumors in neurofibromatosis 1: An overview on management and indications for surgical treatment in our experience.

Neurofibromatosis 1 (NF1) is associated with peripheral nerve tumors (PNTs) in about 30% of cases. In comparison with sporadic forms, NF1 PNTs present some peculiarities: (1) A large prevalence of neurofibromas; (2) the presence of pathognomonic tumoral forms (plexiform neurofibromas); and, (3) a higher incidence (lifetime risk is equal to 8-13%) and an earlier age of onset (2-3 versus 3-6 decades) of malignant peripheral nerve sheath tumors (MPNSTs). For fear of inducing neurological complications, surgical removal of PNTs is generally recommended for symptomatic tumors only. Yet, it can be safely performed by surgeons with expertise in the field. A valid preventive strategy is also essential. Based on the evidence that in NF1, one-third of MPNSTs are consequent to malignant transformation of pre-existing benign tumors, a more aggressive surgical attitude should be advocated.

In lumbosacral plexus injuries can we identify indicators that predict spontaneous recovery or the need for surgical treatment? Results from a clinical study on 72 patients.

BACKGROUND: Post-traumatic lumbosacral plexus injuries seem to be rare events, spontaneously recovering in high percentage: as surgery is often challenging and results in poor outcome, many Authors have advocated conservative treatment only. Nevertheless surgery should not be ruled out: in invalidating injuries, it can restore basic function in the lower extremities.Therefore, it might be necessary to establish guidelines for the management and the indication to surgery in such cases.This study aims to identify indicators predicting spontaneous recovery or the need for surgery. METHOD: The clinical and radiological data of 72 patients with a post-traumatic lumbosacral plexus injury were reviewed. A follow up equal or superior to 3 years is available in 42 cases. RESULTS: Lumbosacral plexus injuries mostly occurred during road accidents. The incidence of associated lesions was relevant: bone injuries were found in 85% of patients, internal lesions in 30% and vascular injuries in 8%.Lumbosacral trunk and sacral plexus palsies were the most frequent injury patterns.Root avulsions were revealed in 23% of cases and only in sacral plexus and complete lumbosacral plexus injuries: L5 and S1 were the roots more prone to avulsions.About 70% of cases recovered spontaneously, mostly in 18 months. Spontaneous recovery was the rule in lumbar plexus and lumbosacral trunk injuries (where root avulsions never occurred) or in sacral and complete lumbosacral plexus palsies due to compression injuries.The causative mechanism correlated with the injury pattern, the associated bone injury being often predictive of the severity of the nerve injury.Lumbosacral plexus injuries occurred in car crashes were generally associated with fractures causing compression on the nerves, thus resulting in injuries often amenable of spontaneous recovery.Motorcycle accidents implied high kinetic energy traumas where traction played an important role, as the high percentage of sacroiliac joint separations demonstrated (found in more than 50% of cases and always associated to root avulsions).Loss of sphincteral control and excruciating leg pain were also invariably associated with avulsions. CONCLUSIONS: Clinical and radiological data can help to predict the occurrence of spontaneous recovery or the need for surgery in post-traumatic lumbosacral plexus injuries.

Perineurioma of the sciatic nerve: a possible cause of idiopathic foot drop in children: report of 4 cases.

The authors report on a loss of foot dorsiflexion in pediatric-age individuals and suggest that the possible cause could be a perineurioma of the sciatic nerve. The authors describe 4 cases in which foot drop in the absence of sensory discomfort was the heralding sign of perineurioma of the sciatic nerve. Magnetic resonance imaging showed a focal enlargement of the sciatic nerve, but the tumor was confined only to its lateral compartment. Treatment in 2 cases involved excision of the affected segment and subsequent graft repair. The two other patients shared the same clinical, radiological, and surgical findings, but no nerve biopsy sample was obtained; the patients underwent only a tibialis posterior muscle transfer. Long-term recovery of nerve function never occurred. Because tumor resection and nerve graft yield no functional results, a tendon transfer to restore walking may be the sole useful surgical procedure in these cases. Removal of the tumor may not be necessary because long-term follow-up confirms that perineuriomas are self-limiting and the final prognosis is favorable.

End-to-side intrapetrous hypoglossal-facialanastomosis for reanimation of the face. Technical note.

The aim of this paper was to report on further experience with a new technique for reanimation of the facial nerve. This procedure allows a straight end-to-side hypoglossal-facial anastomosis without interruption of the 12th cranial nerve or the need for graft interposition. It is technically demanding and time consuming but offers an effective, reliable, and extraordinarily quick means of reinnervating the facial muscles, including the orbicularis oculi muscle, thus avoiding the need for a gold weight in the eyelid or a fascial sling.

Reinnervation of the biceps in C5-7 brachial plexus avulsion injuries: results after distal bypass surgery.

OBJECT: The authors report various techniques, and their results, after performing median and ulnar nerve transfers to reanimate the biceps muscle in C5-7 avulsion-related brachial plexus injuries (BPIs). METHODS: Forty-three adult patients with BPIs of the upper-middle plexus underwent reinnervation of the biceps muscle; neurotization of the musculocutaneous nerve was performed using fascicles from the ulnar nerve (39 cases) and the median nerve (four cases). The different techniques included sectioning, rerouting, and direct suturing of the entire musculocutaneous nerve (35 cases); direct reinnervation of the motor branches of the musculocutaneous nerve (three cases); and reinnervation using small grafts to the motor fascicles that enter the biceps muscle (five cases). Elbow flexion recovery ranged from M2 to M4, according to the patient's age and the level of integrity of the hand. No surgery-related failure occurred. No significant difference in outcome was related to any of the technical variants. In patients younger than age 45 years and exhibiting a normal hand function a score of M4 or better was always achieved. On average, reinnervation occurred 6 months after surgery. There was no clinical evidence of donor nerve dysfunction. CONCLUSIONS: When accurate selection criteria are met, the results after this type of neurotization have proved excellent.

Common peroneal nerve injuries: results with one-stage nerve repair and tendon transfer.

The authors report their experience in the treatment of common peroneal nerve (CPN) injuries using a one-stage procedure of nerve repair and tibialis posterior tendon transfer. A series of 45 patients with traumatic injury and graft repair of the CPN is presented. From 1988 to 1991, the six patients elected for surgery had only nerve repair: five ultimately did not recover, while muscle contraction in the remaining patient was graded M1-2. Since 1991, nerve surgery in our clinic was associated with tendon transfer procedures (39 cases) which were followed by a satisfactory reinnervation rate. Nerve transection and iatrogenic injuries, torsion/dislocation of the knee, complex biosseous fractures of the leg, and gunshot wounds showed excellent to fair results in decreasing order: in nerve sections, muscle recovery scored M3 or M4+ in all the patients, and in nerve ruptures due to severe dislocation of the knee, it was M3 or M4+ in 85% of cases. The association of microsurgical nerve repair and tendon transfer has changed the course of CPN injuries.