["Nerve Surgery" In German-Speaking Countries - Starting With The Nerve Club Up To A Certificate]. / "Nervenchirurgie" im deutschsprachigen Raum ­ vom NervClub zum Zertifikat.

We present the Nerve Club, a community of colleagues originating from german-speaking countries and dedicated to those working in or outside surgery with interest in the peripheral nerve. This article reviews the club´s history and specific characteristics and activities, and highlights the concept of a certificate in nerve surgery. We have annual club meetings and organize every two years a plexus symposium. Also exists a scientific publication award and cooperation with an online based journal dedicated to medical publications in the field of nerve surgery.

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.

Rationale and design of the peripheral nerve tumor registry: an observational cohort study.

AIM: Peripheral nerve tumors (PNT) are rare lesions. To date, no systematic multicenter studies on epidemiology, clinical symptoms, treatment strategies and outcomes, genetic and histopathologic features, as well as imaging characteristics of PNT were published. The main goal of our PNT Registry is the systematic multicenter investigation to improve our understanding of PNT and to assist future interventional studies in establishing hypotheses, determining potential endpoints, and assessing treatment efficacy. METHODS: Aims of the PNT registry were set at the 2015 Meeting of the Section of Peripheral Nerve Surgery of the German Society of Neurosurgery. A study protocol was developed by specialists in PNT care. A minimal data set on clinical status, treatment types and outcomes is reported by each participating center at initial contact with the patient and after 1 year, 2 years, and 5 years. Since the study is coordinated by the Charité Berlin, the PNR Registry was approved by the Charité ethics committee (EA4/058/17) and registered with the German Trials Registry (www.drks.de). On a national level, patient inclusion began in June 2016. The registry was rolled out across Europe at the 2019 meeting of the European Association of Neurosurgery in Dublin. RESULTS: Patient recruitment has been initiated at 10 centers throughout Europe and 14 additional centers are currently applying for local ethics approval. CONCLUSION: To date, the PNT registry has grown into an international study group with regular scientific and clinical exchange awaiting the first results of the retrospective study arm.

Peripheral nerve surgery in Serbia: "Think global, act local" and the privilege of service.

Introduction: The phrase "think globally, act locally", which has often been used to refer to conservation of the environment, highlights the importance of maintaining a holistic perspective and stipulates that each individual has a role to play in their community and larger world. Although peripheral nerve surgery has been largely unemphasized in global neurosurgical efforts, a wide disparity in peripheral nerve surgery is presumed to exist between high-income and low- and middle-income countries. Serbia is an upper middle-income country with a long history of peripheral nerve surgery. Research question: How can understanding the development of peripheral nerve surgery in Serbia advance global education and improve peripheral nerve surgery worldwide? Material and methods: An anecdotal and narrative review of recent advances in peripheral nerve surgery in Serbia was conducted. The World Federation of Neurosurgical Society (WFNS) Peripheral Nerve Surgery Committee discussions on improving peripheral nerve surgery education were summarized. Results: In this manuscript, we describe the application of "think globally, act locally" to peripheral nerve surgery by providing an account of the development of peripheral nerve surgery in Serbia. Then, we report measures taken by the WFNS Peripheral Nerve Surgery Committee to improve education on peripheral nerve surgery in LMICs. Discussion and conclusion: Viewing the development of peripheral nerve surgery in Serbia through the lens of "think globally, act locally" may guide the development of peripheral nerve surgery in LMICs.

Neurogenic Thoracic Outlet Syndrome.

BACKGROUND: Thoracic outlet syndrome (TOS) refers to a group of disorders in which there is compression of and/or damage to the neurovascular structures at the thoracic outlet, i.e., at the transition from chest to neck. The incidence of neurogenic thoracic outlet syndrome (nTOS) is estimated to be 2-3 / 100 000 / year, with an estimated prevalence of 10 / 100 000. Patients present with upper extremity sensorimotor symptoms that are often related to movement. The aim of the present article is to highlight the clinical presentation patterns of nTOS and to provide an overview of its diagnosis and treatment. METHODS: Selective literature search for prospective observational studies and RCTs, including systematic reviews and metaanalyses. RESULTS: There is no multicenter randomized controlled trial available on the treatment of nTOS. Prospective observational studies with a hierarchical study design report a positive effect of physiotherapy in 27-59% of cases. After unsuccessful conservative treatment, up to 56-90% benefit from surgical management. Patients with nTOS are more severely affected compared with those with other forms of TOS and benefit less from transaxillary first rib resection. nTOS patients who underwent supraclavicular decompression without rib resection had excellent surgical outcomes in 27%, good outcomes in 36%, acceptable outcomes in 26%, and poor surgical outcomes in 11% of cases. There is no systematic comparison available of the types of surgical management involved. Also, there is currently no uniform classification available for all medical sub-disciplines. Therefore, interpretation, and comparability of the study results are limited. CONCLUSION: Although nTOS is the most common form of TOS, studies on its treatment are currently limited in terms of numbers and quality. The type of surgical management varies according to the experience and preference of the surgeon, treating specialty, special anatomic features, and clinical symptoms.

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.

Perineurioma: A Rare Entity of Peripheral Nerve Sheath Tumors.

OBJECTIVE: Intraneural perineurioma is a rare tumor entity. It is a benign, very slow growing peripheral nerve sheath tumor that typically occurs in children and young adults. Motor deficits and muscle atrophy are classic presenting symptoms, while sensory deficits are rare at the onset of the disease. Recommended treatment strategies are lacking. We have evaluated the clinical follow-up and our experience with treatment of this rare entity. METHODS: A total of 30 patients with intraneural perineuriomas were assessed retrospectively. Demographic data, clinical symptoms, diagnostic examinations, therapy strategies, and clinical outcome were analyzed. Descriptive statistical methods were used for evaluation. RESULTS: The mean age was 22 years. Eleven women and 19 men were affected. The lesion occurred in the area of the upper extremity in 16 patients and in the area of the lower extremity in 14 patients. The most frequently affected nerve was the sciatic nerve, followed by the radial nerve. All patients showed a motor deficit to some extent. Seventy percent (n = 21) revealed atrophy, 43.3% (n = 13) had sensitive deficits, and 17% (n = 5) suffered of pain. Fascicle biopsies were performed in 26 patients (87%). In four patients (13%), the tumor was completely resected and then reconstructed via nerve grafts. Seventy percent of the patients (n = 21) received a magnetic resonance imaging (MRI) within 5 years postoperatively, in which no progress was shown. CONCLUSIONS: To diagnose perineurioma, it is essential to take a biopsy of an enlarged, nonfunctional fascicle. Furthermore, a long-distance epineuriotomy to decompress the hypertrophic fascicle is reasonable. To preserve the nerves' residual function, a complete resection is not recommended. Results after grafting are poor. One reason for this might be residual tumor cells along the nerve that cannot be visualized. Malignant transformation is not yet reported and tumor growth is stable for years.

Quantitative assessment of intraneural vascular alterations in peripheral nerve trauma using high-resolution neurosonography: technical note.

High-resolution neurosonography (HRNS) has become a major imaging modality in assessment of peripheral nerve trauma in the recent years. However, the vascular changes of traumatic lesions have not been quantitatively assessed in HRNS. Here, we describe the vascular-ratio, a novel HRNS-based quantitative parameter for the assessment of intraneural vascular alterations in patients with nerve lesions. N = 9 patients suffering from peripheral nerve trauma were examined clinically, electrophysiologically and with HRNS (SonoSite Exporte, Fuji). Image analyses using Fiji included determination of the established fascicular ratio (FR), the cross-section ratio (CSR), and as an extension, the calculation of a vascular ratio (VR) of the healthy versus damaged nerve and a muscle perfusion ratio (MPR) in comparison to a healthy control group. The mean VR in the healthy part of the affected nerve (14.14%) differed significantly (p < 0.0001) from the damaged part (VR of 43.26%). This coincides with significant differences in the FR and CSR calculated for the damaged part versus the healthy part and the controls. In comparison, there was no difference between VRs determined for the healthy part of the affected nerve and the healthy controls (14.14% / 17.72%). However, the MPR of denervated muscles was significantly decreased compared to the non-affected contralateral controls. VR and MPR serve as additional tools in assessing peripheral nerve trauma. Image analysis and calculation are feasible. Combined with the more morphologic FR and CSR, the VR and MPR provide a more detailed insight into alterations accompanying nerve trauma.

Rapid and efficient immunomagnetic isolation of endothelial cells from human peripheral nerves.

Endothelial cells (ECs) have gained an increased scientific focus since they were reported to provide guidance for Schwann cells and subsequently following axons after nerve injuries. However, previous protocols for the isolation of nerve-derived ECs from human nerves are ineffective regarding time and yield. Therefore, we established a novel and efficient protocol for the isolation of ECs from human peripheral nerves by means of immunomagnetic CD31-antibody conjugated Dynabeads and assessed the purity of the isolated cells. The easy-to-follow and time-effective isolation method allows the isolation of > 95% pure ECs. The isolated ECs were shown to express highly specific EC marker proteins and revealed functional properties by formation of CD31 and VE-cadherin positive adherens junctions, as well as ZO-1 positive tight-junctions. Moreover, the formation of capillary EC-tubes was observed in-vitro. The novel protocol for the isolation of human nerve-derived ECs allows and simplifies the usage of ECs in research of the human blood-nerve-barrier and peripheral nerve regeneration. Additionally, a potential experimental application of patient-derived nerve ECs in the in-vitro vascularization of artificial nerve grafts is feasible.

Decision Making in Retroperitoneal Nerve Sheath and Nerve-Associated Tumors: A Modular Approach.

BACKGROUND: Surgical treatment of retroperitoneal nerve and nerve-associated tumors is challenging, especially in cases with large extent. A single surgical access may have limitations and jeopardize patients. OBJECTIVE: To present a series of patients to illustrate our individually tailored treatment concept and decision pathway. METHODS: Retrospectively, clinical findings and imaging were related to surgical features and outcome. An algorithm for choice of approach was established. RESULTS: From 2012 to 2017, we operated on n = 13 patients with retroperitoneal tumors, of these n = 9 were included (n = 6 female, n = 3 male). Histological findings included n = 2 schwannomas, n = 2 malignant peripheral nerve sheath tumors, n = 1 non-origin sarcoma, n = 1 perineurioma, n = 1 intraneural ganglion cyst, n = 1 lymphoma, and n = 1 paraganglioma. In n = 6 patients, we used a monoportal (retroperitoneal/transperitoneal) approach; in n = 2 patients, a biportal retroperitoneal to inguinal/transperitoneal to dorsal approach; and in n = 1 patient, a triportal transperitoneal to dorsal to gluteal approach. In n = 2 patients, we performed an open biopsy only; in n = 2 patients, a tumor enucleation; in n = 3 patients, a subtotal function-sparing resection; in n = 1 patient, a complete resection; and in n = 1 patient, intraneural decompression. In n = 1 patient, a new motor deficit appeared. n = 4 patients required further radio-oncological treatment. n = 8/9 patients are alive without tumor progress or recurrence. CONCLUSION: Retroperitoneal nerve or nerve-associated tumors encompass multiple entities. Depending on suspected histology and tumor extension, extensile or combined surgical approaches may be necessary. We present our algorithm for assessment and decision-making regarding surgical access ports and pathways.

Vagus Nerve Stimulation As an Adjunctive Neurostimulation Tool in Treatment-resistant Depression.

Vagus nerve stimulation (VNS) is an approved neurostimulation therapy. The purpose of the method is to treat patients with therapy-resistant depression (TRD). VNS exhibits antidepressive and stabilizing effects. This method is particularly useful as a long-term treatment, in which up to two-thirds of patients respond. The vagus nerve stimulator is positioned on the left vagus nerve during a surgical procedure and is activated telemetrically by a wand connected to a handheld computerized device. The treating physician can perform various adjustments of the vagus nerve stimulator during in-office visits (e.g., by modifying stimulation intensity or stimulation frequency) to achieve maximum therapeutic effects with low side effects. Set-up of the device usually takes several months. Typical side effects include wound infection, temporary salivation, coughing, paralysis of the vocal cords, bradycardia, or even asystole. The patient can stop the VNS by placing a magnet over the generator. The current protocol describes delivery of the specific stimulation tool and methods for adjusting the tuning parameters to achieve the best remission rates in patients with TRD.

The effect of chitosan on the bioaccessibility and intestinal permeability of acyclovir.

Chitosan is object of pharmaceutical research as a candidate permeability enhancer. However, chitosan was recently shown to reduce the oral bioavailability of acyclovir in humans. The effect of chitosan on two processes determining the oral bioavailability of acyclovir, bioaccessibility and intestinal absorption, was now investigated. Acyclovir's bioaccessibility was studied using the dynamic TNO gastro-Intestinal Model (TIM-1). Four epithelial models were used for permeability experiments: a Caco-2 cell model in absence and presence of mucus and both rat and porcine excised intestinal segments. Study concentrations of acyclovir (0.8 g/l) and chitosan (1.6 g/l and 4 g/l) were in line with those used in the aforementioned human study. No effect of chitosan was measured on the bioaccessibility of acyclovir in the TIM-1 system. The results obtained with the Caco-2 models were not in line with the in vivo data. The tissue segment models (rat and porcine intestine) showed a negative trend of acyclovir's permeation in presence of chitosan. The Ussing type chamber showed to be the most biopredictive, as it did point to an overall statistically significantly reduced absorption of acyclovir. This model thus seems most appropriate for pharmaceutical development purposes, in particular when interactions between excipients and drugs are to become addressed.

Fascicular Ratio Pilot Study: High-Resolution Neurosonography-A Possible Tool for Quantitative Assessment of Traumatic Peripheral Nerve Lesions Before and After Nerve Surgery.

BACKGROUND: Clinical and electrophysiological assessments prevail in evaluation of traumatic nerve lesions and their regeneration following nerve surgery in humans. Recently, high-resolution neurosonography (HRNS) and magnetic resonance neurography have gained significant importance in peripheral nerve imaging. The use of the grey-scale-based "fascicular ratio" (FR) was established using both modalities allowing for quantitative assessment. OBJECTIVE: To find out whether FR using HRNS can assess nerve trauma and structural reorganization in correlation to postoperative clinical development. METHODS: Retrospectively, 16 patients with operated traumatic peripheral nerve lesions were included. The control group consisted of 6 healthy volunteers. All imaging was performed with a 15 to 6 MHz ultrasound probe (SonoSite X-Porte; Fujifilm, Tokyo, Japan). FR was calculated using Fiji () on 8-bit-images ("MaxEntropy" using "Auto-Threshold" plug-in). RESULTS: Thirteen of 16 patients required autologous nerve grafting and 3 of 16 extra-intraneural neurolysis. There was no statistical difference between the FR of nonaffected patients' nerve portion with 43.48% and controls with FR 48.12%. The neuromatous nerve portion in grafted patients differed significantly with 85.05%. Postoperatively, FR values returned to normal with a mean of 39.33%. In the neurolyzed patients, FR in the affected portion was 78.54%. After neurolysis, FR returned to healthy values (50.79%). Ten of 16 patients showed clinical reinnervation. CONCLUSION: To our best knowledge, this is the first description of FR using HRNS for quantitative assessment of nerve damage and postoperative structural reorganization. Our results show a significant difference in healthy vs lesioned nerves and a change in recovering nerve portions towards a more "physiological" ratio. Further evaluation in larger patient groups is required.

Predictors of hydrocephalus as a complication of non-traumatic subarachnoid hemorrhage: a retrospective observational cohort study in 107 patients.

BACKGROUND: The predictors of shunt dependency such as amount of subarachnoid blood, acute hydrocephalus (HC), mode of aneurysm repair, clinical grade at admission and cerebro spinal fluid (CSF) drainage in excess of 1500 ml during the 1st week after the subarachnoid hemorrhage (SAH) have been identified as predictors of shunt dependency. Therefore our main objective is to identify predictors of CSF shunt dependency following non-traumatic subarachnoid hemorrhage. METHODS: We performed a retrospective study including patients from January 1st 2012 to September 30th 2014 between 16 and 89 years old and had a non-traumatic subarachnoid hemorrhage in cranial computed tomography (CCT). We excluded patients with the following characteristics: Patients who died 3 days after admittance, lesions in brainstem, previous surgical treatment in another clinic, traumatic brain injury, pregnancy and disability prior to SAH.We performed a descriptive and comparative analysis as well as a logistic regression with the variables that showed a significant difference (p < 0.05). Hence we identified the variables concerning HC after non traumatic SAH and its correlation. RESULTS: One hundred and seven clinical files of patients with non-traumatic SAH were analyzed. Twenty one (48%) later underwent shunt treatment. Shunt patients had significantly clinical and corroborated with doppler ultrasonography vasospasmus (p = 0.015), OR = 5.2. The amount of subarachnoidal blood according to modified Fisher grade was (p = 0.008) OR = 10.9. Endovascularly treated patients were less often shunted as compared with those undergoing surgical aneurysm repair (p = 0.004). CONCLUSION: Vasospasmus and a large amount of ventricular blood seem to be a predictor concerning hydrocephalus after non-traumatic SAH. Hence according to our results the presence of these two variables could alert the treating physician in the decision whether an early shunt implantation < 7 days after SAH should be necessary.

Analysis of regeneration- and myelination-associated proteins in human neuroma in continuity and discontinuity.

BACKGROUND: Neuromas are pathologic nerve distensions caused by a nerve's response to trauma, resulting in a dysfunctional to non-functional nerve. Depending on the severance of the affected nerve, the resulting neuroma can be differentiated into continuous and stump neuroma. While neuroma formation has been investigated in animal models with enormous regenerative capacity, the search for differences in human response to nerve trauma on a molecular level ultimately seeks to identify reasons for functionally successful versus unsuccessful regeneration after peripheral nerve trauma in man. METHODS: In the present study, the regenerative potential of axons and the capability of Schwann cells (SC) to remyelinate regenerating axons was quantitatively and segmentally analyzed and compared within human neuroma in-continuity and discontinuity. RESULTS: For the stump neuroma and the neuroma in-continuity, there was a significant reduction of the total number of axons (86% stump neuroma and 91% neuroma in-continuity) from the proximal to the distal part of the neuroma, while the amount of fibrotic tissue increased, respectively. Labeling the myelin sheath of regenerating axons revealed a remyelination of regenerating axons by SCs in both neuroma types. The segmented analysis showed no distinct alterations in the number and spatial distribution of regenerating, mature, and myelinated axons between continuous and discontinuous neuroma. CONCLUSIONS: The quantitative and segmented analysis showed no distinct alterations in the number and spatial distribution of regenerating, mature, and myelinated axons between continuous and discontinuous neuroma, while the extensive expression of Gap43 in up to 55% of the human neuroma axons underlines their regenerative capacity independent of whether the neuroma is in continuity or discontinuity. Remyelination of Gap43-positive axons suggests that the capability of SCs to remyelinate regenerating axons is preserved in neuroma tissue.

Super-selective cervical nerve root stimulation in contralateral C7 transfer: An intraoperative study.

OBJECTIVE: We designed this study using super-selective intraoperative cervical nerve root stimulation aiming to support decision making about complete or partial contralateral C7 (cC7) nerve root transfer in patients with multiple cervical root avulsion injury. METHODS: Super-selective intraoperative stimulations of anterior, lateral, medial and posterior aspect of C5-C8 nerve roots were performed. Compound muscle action potentials (CMAP) were recorded in the lateral part of the deltoid (DM), long head of biceps brachii (BCM), brachioradial (BRM), long head of triceps brachii (TCM), and extensor digitorum communis (EDC) muscle. Muscle strength was documented immediately after cC7 transfer procedures and on scheduled follow-up visits according to the Medical Research Council (MRC) scale. RESULTS: In the DM, stimulation of the posterior aspect of C5 resulted in the largest CMAP amplitudes (2.0 mV ±â€¯1.9; 80% ±â€¯28.3). The BCM CMAPs induced by the different aspects of C6 all revealed homogenous stimulation results. Stimulation of the lateral aspect of C7 induced the largest amplitude of TCM CMAPs (1.3 mV ±â€¯1.0; 67.1% ±â€¯43.3). CMAP amplitudes of individual muscles and individual contributions of cervical nerve roots to the TCM varied between subjects. Overall donor side morbidity was low, no permanent motor deficit occurred. CONCLUSION: A super-selective intraoperative cervical nerve root stimulation may help minimize donor side morbidity in transfer procedures. Individual differences of cervical nerve root innervation pattern need to be addressed in future electrophysiological studies. SIGNIFICANCE: Our study outlines individual differences of cervical nerve root innervation pattern.

Nutritional Control of DNA Replication Initiation through the Proteolysis and Regulated Translation of DnaA.

Bacteria can arrest their own growth and proliferation upon nutrient depletion and under various stressful conditions to ensure their survival. However, the molecular mechanisms responsible for suppressing growth and arresting the cell cycle under such conditions remain incompletely understood. Here, we identify post-transcriptional mechanisms that help enforce a cell-cycle arrest in Caulobacter crescentus following nutrient limitation and during entry into stationary phase by limiting the accumulation of DnaA, the conserved replication initiator protein. DnaA is rapidly degraded by the Lon protease following nutrient limitation. However, the rate of DnaA degradation is not significantly altered by changes in nutrient availability. Instead, we demonstrate that decreased nutrient availability downregulates dnaA translation by a mechanism involving the 5' untranslated leader region of the dnaA transcript; Lon-dependent proteolysis of DnaA then outpaces synthesis, leading to the elimination of DnaA and the arrest of DNA replication. Our results demonstrate how regulated translation and constitutive degradation provide cells a means of precisely and rapidly modulating the concentration of key regulatory proteins in response to environmental inputs.

Cdc48-independent proteasomal degradation coincides with a reduced need for ubiquitylation.

Ubiquitin fusion degradation (UFD) substrates are delivered at the proteasome by a handover mechanism involving the ubiquitin-selective chaperone Cdc48 and the ubiquitin shuttle factor Rad23. Here, we show that introduction of a 20 amino acid peptide extension not only rendered degradation independent of Cdc48, in line with the model that this chaperone is involved in early unfolding events of tightly folded substrates, but at the same time relieved the need for efficient polyubiquitylation and the ubiquitin shuttle factor Rad23. Removal of the ubiquitylation sites in the N-terminal UFD signal made the degradation of this substrate strictly dependent on the peptide extension and also on Cdc48 and, importantly the presence of a functional ubiquitylation machinery. This suggests that the extension in the absence of N-terminal ubiquitylation sites is not properly positioned to engage the unfoldase machinery of the proteasome. Thus the need for efficient ubiquitylation and Cdc48 in facilitating proteasomal degradation are tightly linked but can be bypassed in the context of UFD substrates by the introduction of an unstructured extension. Our data suggest that polyubiquitin-binding complexes acting upstream of the proteasome, rather than the proteasome itself, can be primary determinants for the level of ubiquitylation required for protein degradation.

Endoscopically assisted piriformis-to-knee surgery of sciatic, peroneal, and tibial nerves: technical note.

BACKGROUND: Proximal lesions of the sciatic nerve are often difficult to diagnose and to treat properly. In particular, if there are posttraumatic or postoperative alterations, imaging might not identify the level and location of lesion. Due to the sciatic nerve anatomy, the same is true for clinical and electrophysiological evaluation with a risk of delayed surgery and, thus, unsuccessful surgery. Therefore, in some unclear cases, surgical exploration of the whole sciatic nerve and its divisions could be the only means to determine the correct diagnosis and allow prompt treatment to produce the best clinical outcome. OBJECTIVE: To describe a novel minimally invasive technique to explore and treat patients with proximal sciatic, peroneal, and tibial nerve lesions. Intraoperative findings, surgical considerations, and complications are presented. METHODS: From January 2012 to November 2013, 9 consecutive patients with lesions of the sciatic, peroneal, and tibial nerves underwent endoscopy and were treated. The technical considerations of these cases are presented with regard to the retrospectively collected clinical and surgical data to evaluate the pros and cons of the technique. RESULTS: A subgluteal incision, as the primary endoscopic port, was used in all 9 patients. An additional mid-thigh and fibular head incision was thought necessary in 3 patients. An extension of the approach by a secondary transgluteal incision was performed in 4 patients. In 2 of these sciatic lesions, autologous nerve grafts were placed. One perineurioma was detected and bioptically secured. There were no complications. Six patients experienced pain relief; in 6, we observed motor improvement. The mean follow-up was 9.5 months. CONCLUSION: The endoscopically assisted single- to multiportal sciatic exploration technique provides excellent visualization that enables nerve inspection, lesion detection, and decompression, and obviates the need for more extensive approaches in cases of unclear sciatic nerve pathology. By adding several ports, whole-length exploration of the sciatic from the notch to fibular head level is feasible.