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OBJECTIVE High cervical spinal cord injury (SCI) results in complete loss of upper-limb function, resulting in debilitating tetraplegia and permanent disability. Spontaneous motor recovery occurs to varying degrees in some patients, particularly in the 1st year postinjury. However, the impact of this upper-limb motor recovery on long-term functional outcomes remains unknown. The objective of this study was to characterize the impact of upper-limb motor recovery on the degree of long-term functional outcomes in order to inform priorities for research interventions that restore upper-limb function in patients with high cervical SCI. METHODS A prospective cohort of high cervical SCI (C1–4) patients with American Spinal Injury Association Impairment Scale (AIS) grade A–D injury and enrolled in the Spinal Cord Injury Model Systems Database was included. Baseline neurological examinations and functional independence measures (FIMs) in feeding, bladder management, and transfers (bed/wheelchair/chair) were evaluated. Independence was defined as score ≥ 4 in each of the FIM domains at 1-year follow-up. At 1-year follow-up, functional independence was compared among patients who gained recovery (motor grade ≥ 3) in elbow flexors (C5), wrist extensors (C6), elbow extensors (C7), and finger flexors (C8). Multivariable logistic regression evaluated the impact of motor recovery on functional independence in feeding, bladder management, and transfers. RESULTS Between 1992 and 2016, 405 high cervical SCI patients were included. At baseline, 97% of patients had impaired upper-limb function with total dependence in eating, bladder management, and transfers. At 1 year of follow-up, the largest proportion of patients who gained independence in eating, bladder management, and transfers had recovery in finger flexion (C8) and wrist extension (C6). Elbow flexion (C5) recovery had the lowest translation to functional independence. Patients who achieved elbow extension (C7) were able to transfer independently. On multivariable analysis, patients who gained elbow extension (C7) and finger flexion (C8) were 11 times more likely to gain functional independence (OR 11, 95% CI 2.8–47, p < 0.001) and patients who gained wrist extension (C6) were 7 times more likely to gain functional independence (OR 7.1, 95% CI 1.2–56, p = 0.04). Older age (≥ 60 years) and motor complete SCI (AIS grade A–B) reduced the likelihood of gaining independence. CONCLUSIONS After high cervical SCI, patients who gained elbow extension (C7) and finger flexion (C8) had significantly greater independence in feeding, bladder management, and transfers than those with recovery in elbow flexion (C5) and wrist extension (C6). Recovery of elbow extension (C7) also increased the capability for independent transfers. This information can be used to set patient expectations and prioritize interventions that restore these upper-limb functions in patients with high cervical SCI.

OBJECTIVE Patients with brachial plexus avulsion (BPA) experience chronic deafferentation pain characterized by two patterns: continuous background pain and electrical shooting paroxysmal attacks. The authors’ aim was to report the effectiveness and safety of dorsal root entry zone (DREZ) lesioning in relieving the two forms of pain over short and long periods. METHODS All patients who underwent DREZ lesioning performed by the senior author for medically refractory BPA-related pain between July 1, 2016, and June 30, 2020, in Johns Hopkins Hospital were followed up. The intensity levels for continuous and paroxysmal pains were evaluated using the numeric rating scale (NRS) preoperatively and at 4 time points postsurgery, including the day of discharge, with a mean hospital stay of 5.6 ± 1.8 days; first postoperative clinic visit (33.0 ± 15.7 days); short-term follow-up (4.0 ± 1.4 months); and long-term follow-up (3.1 ± 1.3 years). The percent of pain relief according to the NRS was categorized into excellent (≥ 75%), fair (25%–74%), and poor (< 25%). RESULTS A total of 19 patients were included, with 4 (21.1%) lost to long-term follow-up. The mean age was 52.7 ± 13.6 years; 16 (84.2%) were men, and 10 (52.6%) had left-sided injuries. A motor vehicle accident was the most common etiology of BPA (n = 16, 84.2%). Preoperatively, all patients had motor deficits, and 8 (42.1%) experienced somatosensory deficits. The greatest pain relief was observed at the first postoperative and short-term follow-up visits, with the lowest proportions of patients having continuous pain (26.3% and 23.5%, respectively) and paroxysmal pain (5.3% and 5.9%, respectively). Also, the highest reductions in mean NRS scores were observed for first postoperative and short-term follow-up visits (continuous 1.1 ± 2.1 and 1.1 ± 2.3; paroxysms 0.4 ± 1.4 and 0.5 ± 1.7, respectively) compared to the preoperative symptomatology (continuous 6.7 ± 3.0; paroxysms 7.9 ± 4.3) (p < 0.001). Most patients had excellent relief of continuous pain (82.4% and 81.3%) and of paroxysms (90.9% and 90.0%) at the first postoperative visit and short-term follow-up visit, respectively. The pain relief benefits had diminished by 3 years after surgery but remained significantly better than in the preoperative assessment. At the last evaluation, the proportion of patients achieving excellent relief of paroxysmal pain (66.7%) was double that for continuous pain (35.7%) (p < 0.001). New sensory phenomena were observed among 10 patients (52.6%), and 1 patient developed a motor deficit. CONCLUSIONS DREZ lesioning is an effective and safe option for relieving BPA-associated pain, with good long-term outcomes and better benefits for paroxysmal pain than for the continuous pain component.

Background Up to 10% of cervical spine surgeries are complicated by postoperative weakness. Although many patients recover with nonoperative management, some require surgery for restoration of function. Objective To present the indications and outcomes of patients undergoing nerve transfers after developing weakness secondary to cervical spine decompression. Methods A retrospective review of patients from 2 academic medical centers who underwent nerve transfer for C5–6 root injury after cervical spine surgery was performed. Results Of the 10 treated patients, 9 experienced recovery at last follow-up, demonstrating improvements in strength and motion in the affected muscles. Successful nerve transfers occurred between 3 and 8 months after the index spinal surgery and included spinal accessory nerve to suprascapular nerve, triceps branch to anterior division of the axillary nerve, and/or ulnar or median fascicles to motor branches of the musculocutaneous nerve. The unsuccessful patient underwent nerve transfer surgery approximately 11 months after the index operation and failed to obtain functional recovery. Conclusions Patients who experience C5–6 weakness after cervical spine surgery should be evaluated and considered for nerve transfer surgery if they have continued severe functional deficits at 6 months postoperatively. Earlier referral for nerve transfer is associated with improved functional outcomes in this cohort.

Background Acute flaccid myelitis (AFM) is an acute-onset anterior horn disease resulting in flaccid paralysis of extremities, trunk, facial, and cervical musculature in children following upper respiratory or gastrointestinal viral illness. Nerve transfer procedures have been shown to restore function. Objective To present a technical description of sciatic-to-femoral nerve transfers in 4 children with AFM. Methods Retrospective review of relevant cases was performed. Results A total of 4 cases are presented of young children with persistent quadriparesis in the setting of AFM, presenting between 4 and 15 mo following initial diagnosis. Electromyography showed denervation of muscles innervated by the femoral nerve, with sparing of the sciatic distribution. The obturator nerve was also denervated in all patients. We therefore elected to pursue sciatic-to-femoral transfers to restore active knee extension. These transfers involved end-to-end coaptation of a sciatic nerve fascicle to the femoral nerve motor branches supplying quadriceps muscles. Conclusion We present technical descriptions of bilateral sciatic-to-femoral nerve neurotization for the restoration of quadriceps function in 4 patients with AFM. The sciatic nerve fascicles are a reasonable alternative donor nerve for patients with proximal muscle paralysis and limited donor options in the lower extremity.

Neurogenic thoracic outlet syndrome (NTOS) is the most common form of thoracic outlet syndrome. However, NTOS has remained difficult to diagnose and treat successfully. The purpose of the present study was to generate a predictive clinical calculator for postoperative outcomes after first rib resection (FRR) for NTOS.We performed a retrospective review of patients who had undergone FRR for NTOS at a single tertiary care institution between 2016 and 2020. A multivariate stepwise logistic regression analysis was performed to assess the association of the percentage of improvement after FRR with the patient baseline characteristics, pertinent clinical characteristics, and diagnostic criteria set by the Society for Vascular Surgery. The primary outcome was subjective patient improvement after FRR. A prediction risk calculator was developed using backward stepwise multivariate logistic regression coefficients. Bootstrapping was used for internal validation.A total of 208 patients (22.2% male; mean age, 35.8 ± 12.8 years; median follow-up, 44.9 months) had undergone 243 FRRs. Of the 208 patients, 94.7% had had symptoms localized to the supraclavicular area, and 97.6% had had symptoms in the hand. All the patients had had positive symptoms reproduced by the elevated arm stress test and upper limb tension test. Another reasonably likely diagnosis was absent for all the patients. Of the 196 patients who had received a lidocaine injection, 180 (93.3%) had experienced improvement of NTOS symptoms. Of the 95 patients who had received a Botox injection, 82 (74.6%) had experienced improvement of NTOS symptoms. Receiver operating characteristic curve analysis was used to assess the model. The area under the curve for the backward stepwise multivariate logistic regression model was 0.8. The multivariate logistic regression analyses revealed that the significant predictors of worsened clinical outcomes included hand weakness (adjusted odds ratio [aOR], 4.28; 95% confidence interval [CI], 1.04-17.74), increasing age (aOR, 0.93; 95% CI, 0.88-0.99), workers' compensation or litigation case (aOR, 0.09; 95% CI, 0.01-0.82), and symptoms in the dominant hand (aOR, 0.20; 95% CI, 0.05-0.88).Using retrospective data from a single-institution database, we have developed a prediction calculator with moderate to high predictive ability, as demonstrated by an area under the curve of 0.8. The tool (available at: https://jhhntosriskcalculator.shinyapps.io/NTOS_calc/) is an important adjunct to clinical decision-making that can offer patients and providers realistic and personalized expectations of the postoperative outcome after FRR for NTOS. The findings from the present study have reinforced the diagnostic criteria set by the Society for Vascular Surgery. The calculator could aid physicians in surgical planning, referrals, and counseling patients on whether to proceed with surgery.

Plexiform Neurofibromas (PN) are a common manifestation of the genetic disorder neurofibromatosis type 1 (NF1). These benign nerve sheath tumors often cause significant morbidity, with treatment options limited historically to surgery. There have been tremendous advances over the past two decades in our understanding of PN, and the recent regulatory approvals of the MEK inhibitor selumetinib are reshaping the landscape for PN management. At present, there is no agreed upon PN definition, diagnostic evaluation, surveillance strategy, or clear indications for when to initiate treatment and selection of treatment modality. In this review, we address these questions via consensus recommendations from a panel of multidisciplinary NF1 experts.

Intraoperative nerve action potential (NAP) recording permits direct study of an injured nerve for functional assessment of lesions in continuity. Stimulus artifact contamination often hampers NAP recording and interferes with its interpretation. In the present study, we evaluated the artifact reduction method using alternating polarity in peripheral nerve recording. Our study was conducted under controlled conditions in laboratory animals. NAPs were recorded from surgically exposed median or ulnar nerves. For the artifact reduction method with alternating polarity, two sequential recordings, one with normal and one with reversed stimulus polarity, were acquired and the signals from this recording pair were averaged. Simulation was also performed to further evaluate the effects of alternating polarity on the waveforms. The results are as follows: First, we found that this method worked for recordings with unsaturated electrical stimulus artifacts. Second, slightly unequal latencies occurred in an NAP pair, and this inequality contributed to a minimal loss of NAP amplitudes when averaging the two recordings. Third, perfect artifact cancelation and minimal signal loss were also demonstrated by simulation. Finally, we applied the method during nerve inching and demonstrated its usefulness in intraoperative NAP recordings as the method made the recording more resilient to short conduction distances. Thus, our findings demonstrate that this artifact reduction method can be used as a supplemental tool together with our previously described bridge grounding technique or the nonlifting nerve recording configuration to further improve intraoperative peripheral nerve recording. The method can be applied in clinical settings.

OBJECTIVEIntraoperative nerve action potential (NAP) recording is a useful tool for surgeons to guide decisions on surgical approaches during nerve repair surgeries. However, current methods remain technically challenging. In particular, stimulus artifacts that contaminate or mask the NAP and therefore impair the interpretation of the recording are a common problem. The authors’ goal was to improve intraoperative NAP recording techniques by revisiting the methods in an experimental setting.METHODSFirst, NAPs were recorded from surgically exposed peripheral nerves in monkeys. For the authors to test their assumptions about observed artifacts, they then employed a simple model system. Finally, they applied their insights to clinical cases in the operating room.RESULTSIn monkey peripheral nerve recordings, large stimulus artifacts obscured NAPs every time the nerve segment (length 3–5 cm) was lifted up from the surrounding tissue, and NAPs could not be recorded. Artifacts were suppressed, and NAPs emerged when “bridge grounding” was applied, and this allowed the NAPs to be recorded easily and reliably. Tests in a model system suggested that exaggerated stimulus artifacts and unmasking of NAPs by bridge grounding are related to a loop effect that is created by lifting the nerve. Consequently, clean NAPs were acquired in “nonlifting” recordings from monkey peripheral nerves. In clinical cases, bridge grounding efficiently unmasked intraoperative NAP recordings, validating the authors’ principal concept in the clinical setting and allowing effective neurophysiological testing in the operating room.CONCLUSIONSTechnical challenges of intraoperative NAP recording are embedded in the current methods that recommend lifting the nerve from the tissue bed, thereby exaggerating stimulus artifacts by a loop effect. Better results can be achieved by performing nonlifting nerve recording or by applying bridge grounding. The authors not only tested their findings in an animal model but also applied them successfully in clinical practice.

BACKGROUND Postoperative C5 palsy is a debilitating complication following posterior cervical decompression. OBJECTIVE To create a simple clinical risk score predicting the occurrence of C5 palsy. METHODS We retrospectively reviewed all patients who underwent posterior cervical decompressions between 2007 and 2017. Data was randomly split into training and validation datasets. Multivariable analysis was performed to construct the model from the training dataset. A scoring system was developed based on the model coefficients and a web-based calculator was deployed. RESULTS The cohort consisted of 415 patients, of which 65 (16%) developed C5 palsy. The optimal model consisted of: mean C4/5 foraminal diameter (odds ratio [OR] = 9.1 for lowest quartile compared to highest quartile), preoperative C5 radiculopathy (OR = 3.5), and dexterity loss (OR = 2.9). The receiver operating characteristic yielded an area under the curve of 0.757 and 0.706 in the training and validation datasets, respectively. Every characteristic was worth 1 point except the lowest quartile of mean C4/5 foraminal diameter, which was worth 2 points, and the factors were summarized by the acronym F2RaD. The median predicted probability of C5 palsy increased from 2% in patients with a score of 0 to 70% in patients with a score of 4. The calculator can be accessed on https://jhuspine2.shinyapps.io/FRADscore/. CONCLUSION This study yielded a simplified scoring system and clinical calculator that predicts the occurrence of C5 palsy. Individualized risk prediction for patients may facilitate better understanding of the risks and benefits for an operation, and better prepare them for this possible adverse outcome. Furthermore, modifying the surgical plan in high-risk patients may possibly improve outcomes.

Localized hypertrophic neuropathy is a rare Schwann cell proliferation that usually affects single nerves from the extremities, and it is of unclear etiology in its pure form. RASopathies are a defined group of genetic diseases with overlapping clinical features, usually secondary to germline mutations in genes encoding either components or regulators of the RAS/MAPK pathway. Herein, we report an 11-year-old boy presenting with café au lait spots and right leg length discrepancy. A fascicular nerve biopsy of the tibial nerve demonstrated a Schwann cell proliferation with prominent onion-bulb formation, satisfying criteria for localized hypertrophic neuropathy. Molecular genetic analysis demonstrated identical KRAS mutations (c38_40dupGCG) in the peripheral nerve lesion and melanocytes from café au lait spots, but not in blood, supporting a diagnosis of a KRAS-mediated rasopathy with mosaicism. Immunohistochemical staining in the peripheral nerve lesion demonstrated strong pERK staining consistent with downstream MAPK pathway activation. This report suggests that at least a subset of localized hypertrophic neuropathies are bonafide, well-differentiated Schwann cell neoplasms developing through oncogenic RAS signaling, which provides new insights into the controversial entity historically known as localized hypertrophic neuropathy.

Study Design International survey. Objectives C5 palsy (C5P) is a neurological complication affecting 5-10% of patients after cervical decompression surgery. Most cases improve with conservative treatment; however, nearly 20% of patients may be left with residual deficits. Guidelines are lacking on C5P management and timing of surgical intervention. Therefore, we sought to survey peripheral nerve surgeons on their management of C5P. Methods An online survey was distributed centered around a patient with C5P after posterior cervical decompression and fusion. Questions included surgeon demographics, diagnostic modalities, and timing and choice of operation. Responses were summarized and the chi-squared and Kruskal-Wallis H tests were used to examine differences across specialties. Results A total of 154 surgeons responded to the survey, of which 59 (38%) indicated that they manage C5P cases. Average time prior to operating was 4.5 ± 2.2 months for complete injuries and 6.6 ± 3.2 months for partial injuries, with neurosurgeons significantly more likely to wait longer periods for complete ( P = .01) and partial injuries ( P = .03). Foraminotomies were selected by 19% of surgeons, while 92% selected nerve transfers. Transfer of the ulnar nerve to the musculocutaneous nerve was the most common choice (81%), followed by transfer of the radial nerve to the axillary nerve (58%). Conclusion Consensus exists among peripheral nerve surgeons on the use of nerve transfers for surgical treatment in cases with severe motor weakness failing to improve. Most surgeons advocate for early intervention in complete injuries. Disagreement concerns the type of nerve transfer employed, timing of surgery, and efficacy of foraminotomy.

Malignant peripheral nerve sheath tumors (MPNST) are the deadliest cancer that arises in individuals diagnosed with neurofibromatosis and account for nearly 5% of the 15,000 soft tissue sarcomas diagnosed in the United States each year. Comprised of neoplastic Schwann cells, primary risk factors for developing MPNST include existing plexiform neurofibromas (PN), prior radiotherapy treatment, and expansive germline mutations involving the entire NF1 gene and surrounding genes. PN develop in nearly 30-50% of patients with NF1 and most often grow rapidly in the first decade of life. One of the most important aspects of clinical care for NF1 patients is monitoring PN for signs of malignant transformation to MPNST that occurs in 10-15% of patients.We perform aneuploidy analysis on ctDNA from 883 ostensibly healthy individuals and 28 patients with neurofibromas, including 7 patients with benign neurofibroma, 9 patients with PN and 12 patients with MPNST. Overall sensitivity for detecting MPNST using genome wide aneuploidy scoring was 33%, and analysis of sub-chromosomal copy number alterations (CNAs) improved sensitivity to 50% while retaining a high specificity of 97%. In addition, we performed mutation analysis on plasma cfDNA for a subset of patients and identified mutations in NF1, NF2, RB1, TP53BP2, and GOLGA2. Given the high throughput and relatively low sequencing coverage required by our assay, liquid biopsy represents a promising technology to identify incipient MPNST.

Schwannomatosis is a multiple tumor syndrome in which patients develop benign tumors along peripheral nerves throughout the body. The first symptom with which schwannomatosis patients often present, prior to discovery of tumors, is pain. This pain can be debilitating and is often inadequately alleviated by pharmacological approaches. Schwannomatosis-associated pain can be localized to the area of a tumor, or widespread. Moreover, not all tumors are painful, and the occurrence of pain is often unrelated to tumor size or location. We speculate that some individual tumors, but not others, secrete factors that act on nearby nerves to augment nociception by producing neuronal sensitization or spontaneous neuronal firing. We created cell lines from human SWN tumors with varying degrees of pain. We have found that conditioned medium (CM) collected from painful SWN tumors, but not that from nonpainful SWN tumors, sensitized DRG neurons, causing increased sensitivity to depolarization by KCl, increased response to noxious TRPV1 and TRPA1 agonists and also upregulated the expression of pain-associated genes in DRG cultures. Multiple cytokines were also detected at higher levels in CM from painful tumors. Taken together our data demonstrate a differential ability of painful versus non-painful human schwannomatosis tumor cells to secrete factors that augment sensory neuron responsiveness, and thus identify a potential determinant of pain heterogeneity in schwannomatosis.

Thoracic meningoceles and dural ectasia are less commonly recognized manifestations of neurofibromatosis 1 (NF1). Rarely, large thoracic meningoceles may become compressive and lead to respiratory compromise secondary to lung compression. Surgical goals aim to increase lung aeration through decreasing the size of the meningocele through shunting, excision or repair of the meningocele, and varying degrees of dural tube reconstruction. There is no agreement on the best approach for large, symptomatic meningoceles. Here, we discuss the case of a 41-year-old woman with NF1 who presented with dyspnea and enlargement of a large, 19 cm thoracic meningocele. A multidisciplinary team of thoracic, plastic, and neurological surgery participated in the operation to excise the meningocele and reconstruct the dural tube without the need for subsequent shunting of spinal fluid. We also systematically review the literature on thoracic meningoceles in NF1 to understand the optimal treatment of this pathology.

Comparative effectiveness research has a vital role in recent health reform and policies. Specialty training is one of these provider-side variables and surgeons who were trained in different specialties may have different outcomes upon performing the same procedure. The objective of this retrospective 1:1 propensity score-matched cohort study was to investigate the impact of spine surgeon specialty (neurosurgery vs orthopedic surgery) on early perioperative outcome measures of elective posterior/transforaminal lumbar interbody fusion for degenerative spine diseases. 22,176 patients were reviewed from ACS-NSQIP database. Propensity score matching and subgroup analysis were utilized. After controlling for baseline characteristics in both groups (single/multi-level PLIF/TLIF), patients operated on by neurosurgeons were more likely to have longer operation time (239 vs 205 minutes / 276 vs 254 minutes), shorter total hospital stay (75 vs 96 hours / 85 vs 103 hours), lower return to operating room rates within the same admission (2.2% vs 4.2% / 2.5% vs 4.3%), lower non-home discharge (8.8% vs 12.7% / 10.8% vs 18.2%), lower discharge rate after postoperative day 3 (28% vs 31.8% / 38.1% vs 43.9%), lower readmission rates (4.4% vs 6.5% / 4.5% vs 7.5%) and lower perioperative blood transfusion rate (2.7% vs 6.0% / 11.0% vs 14.1%), (p

Schwannomatosis is a relatively new addition to the neurofibromatosis family of disorders. Occurring in only 1 in every 70,000 live births, it is the rarest neurofibromatosis and is characterized by the proliferation of peripheral nerve and spinal schwannomas. Genetic studies have identified SMARCB1 and LZTR1 as playing key roles in the pathogenesis of this disease. Patients most commonly present in the fourth or fifth decade of life with chronic and neuropathic pain, the medical management of which forms the core of therapy in this patient population. Surgical excision appears to have a role in the treatment of medically refractory, radicular, or neuropathic pain that is attributable to the schwannoma. At present no systemic therapies exist, and this remains an area of key interest for investigation.

Malignant peripheral nerve sheath tumors constitute around 5% of yearly incident soft tissue sarcomas in the United States, with around half of cases occurring in neurofibromatosis type 1, and prognosis remains poor despite multimodal therapy. Guidelines based on a high level of evidence for the use of adjunct radiotherapy and chemotherapy are lacking, but general recommendations on the most common indications can be made. In general, radiotherapy is employed as adjuvant treatment in intermediate- or high-grade tumors that are more than 5 cm in size or after marginal excision of low-grade lesions. Chemotherapy is mainly utilized in metastatic disease and in cases where preoperative chemotherapy may downstage tumors to improve surgical outcome. Targeted therapies are currently being investigated in clinical trials and constitute the main focus of future research endeavors aimed at prolonging survival. Multimodal therapy in specialized centers and a multidisciplinary approach remain crucial for achieving optimal outcome.

Objective In this study, we sought to characterize contemporary trends in cost and utilization of spinal cord stimulation (SCS). Methods The Healthcare Cost and Utilization Project−National Inpatient Sample was queried for inpatient admissions from 2008 to 2014 where SCS was performed. We then determined the rates and costs of SCS performed in this time frame to treat diagnoses that we classified as device-related complications, degenerative spine disease, pain syndromes, and neuropathies/neuritis/nerve lesions. Least-squares regression was performed to determine the yearly trends for each indication adjusted by the total number of yearly hospitalizations for that diagnosis. Results We identified a total of 6876 admissions in whom an SCS was performed. The overall rate of inpatient SCS procedures performed has decreased by 45% from 2008 to 2014 (14.0 to 7.7 procedures per 100,000 admissions). Adjusted analysis for yearly trends also demonstrated a declining trend for all indications; however, this was not found to be statistically significant, except for device-related complications (P = 0.004). The median inflation-adjusted cost of an admission where SCS was performed increased slightly by 7.4% from $26,200 (IQR: $16,700−$33,800) in 2008 to $28,100 (IQR: $19,600−$36,900) in 2014. Billed hospital charges demonstrated a significant increase with median inflation-adjusted admission charge of $66,068 in 2008 to $110,672 in 2014. Conclusions Despite a declining contemporary trend in inpatient SCS, an increase was noted in admission costs and hospital charges. A significant declining trend was noted in revision SCS implantations due to device-related complications.

C5 palsy affects approximately 5% to 10% of patients undergoing cervical spine surgery. It has a significant negative impact on patient quality-of-life outcomes and healthcare costs. Although80% of patients improve, some are left with persistent, debilitating deficits. Our objective was to examine if electrodiagnostic testing could be used to successfully identify patients likely to experience complete, partial, and no recovery.Patients undergoing posterior cervical decompression and fusion at a single institution over a 10-year period were identified. Those experiencing postoperative C5 palsy were included. Outcomes examined included motor recovery of the affected deltoid as a function of time, and changes in electrodiagnostic testing as a function of time since injury. Electrodiagnostic testing included electromyography and was sub-analyzed by time of acquisition postinjury. Deltoid strength was graded on manual motor testing using the 5-point medical research council grading system.Of 77 patients experiencing C5 palsy, 29 had postoperative electrodiagnostic testing. Patients experiencing complete recovery on average achieved functional (4/5) strength by 6-weeks post injury and 4+ per 5 strength by 6-months. Those experiencing partial recovery only achieved antigravity strength (3/5) by 6-weeks and low-function (4-/5) strength by 6-months. Electrodiagnostic testing performed 6-weeks to 6-months postinjury demonstrated that those experiencing complete recovery were more likely to have normal motor unit (MU) recruitment than those experiencing partial (p.001) or no recovery (p=.008). The presence of ≥2+ fibrillation on tests acquired ≤6-weeks of injury identified patients unlikely to experience any recovery with a positive predictive value (PPV) of 88.9%. The presence of normal MU recruitment on tests acquired 6-weeks to 6-months postinjury identified patients likely to experience complete recovery with a PPV of 87.5%.Electrodiagnostic testing may be a valuable means of differentiating between patients with C5 palsy likely to experience complete, partial, or no recovery. Testing between 6-weeks and 6-months post onset may aid in identifying those least likely to have a complete recovery. No MUs at 4 to 6-months, or reduced units with strength that is not improving, portends a poor long-term outcome. In this population, peripheral nerve transfers may be considered sooner.

Intraneural perineuriomas are rare benign neoplasms. The gene associated with neurofibromatosis 2 (NF2) is located on chromosome 22q12, and mutations in NF2 are commonly seen in soft tissue perineuriomas. However, an association between NF2 mutations and intraneural perineuriomas (INPs) has not been well established. We present a 20-year-old male with NF2, multiple schwannomas and an intraneural perineurioma in the radial nerve at the spiral groove. Sequencing of NF2, SMARCB1, and LZTR1 was performed and demonstrated loss of the long arm of chromosome 22 including NF2, SMARCB1, and LZTR1, and a constitutional NF2:c.(-4577_-854)_(45-185)del alteration. We review the literature supporting two mutually exclusive pathways involving NF2 and TRAF7 mutations that lead to the development of INPs.

Background Robotic-assisted techniques have been implemented in the surgical treatment of tumors in the pelvis, abdomen, and thorax. In pelvic tumors, robotic-assisted techniques evade the need for sizable surgical exposure, but make stimulation of the nerves of the sacral plexus very difficult. Objective To describe how laparoscopic robotic-assisted surgery can couple with tools such as the nerve stimulator to aid in the resection of presacral masses emanating from the neural elements and potentially improve neurological outcome by preventing inadvertent injury to involved nerves. Methods A patient with a large presacral ganglioneuroma underwent resection using the DaVinci system (Intuitive Surgical, Sunnyvale, California) for robotic assistance. A nerve stimulator was coupled to the bipolar cautery instrument of the DaVinci robot to define the presence of functional nerves in the surroundings of the tumor. Results By coupling a nerve stimulator to the bipolar cautery instrument of the DaVinci robot (Intuitive Surgical), it was possible to identify important neural structures in close proximity to the tumor. After identifying functional nerves, the surgeon was able to preserve them and preserve neurological function avoiding motor dysfunction. Conclusion The use of a nerve stimulator coupled to the bipolar cautery instrument of the DaVinci robot (Intuitive Surgical) during laparoscopic, robotic-assisted surgery for resection of presacral masses is safe and feasible. In addition to the preoperative evaluation, intraoperative monitoring and stimulation of nerves in close proximity to the tumor and also exiting through neural foramina involved by the tumor allowed the surgeon to understand the anatomy and preserve neurological function while obtaining optimal surgical resection.

OBJECTIVE This study aimed to investigate the diagnostic accuracy of magnetic resonance (MR) imaging for categorizing sciatic peripheral nerve injury (PNI) as high-grade (Sunderland grades IV-V) or low-grade (Sunderland grades I-III) PNI. METHODS In this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study, consecutive MR imaging of the pelvis and thighs, performed for the evaluation of traumatic sciatic neuropathy, was reviewed for sciatic nerve signal intensity, size, architectural distortion, bulbous enlargement, perineural fibrosis, discontinuity, and muscle denervation changes. Clinical data, electrodiagnostic testing, and surgical history were used to determine PNI grade (high, low). Descriptive and diagnostic performance statistics were applied. RESULTS Of 24 patients, there were 12 high-grade and 12 low-grade PNI. There was no significant difference in signal intensity or size between high-grade and low-grade PNI (1.3 ± 0.5 cm vs 0.9 ± 0.3 cm, P = 0.09). The sensitivity and specificity for the presence of individual features in predicting high-grade injury were 83% and 67% for architectural distortion, 58% and 75% for bulbous enlargement, 50% and 83% for perineural fibrosis, 25% and 100% for discontinuity, and 67% and 75% for skeletal muscle denervation changes, respectively. Overall, the sensitivity and specificity of MR imaging for categorizing sciatic PNI as high grade was 75% and 83%, respectively. CONCLUSIONS The MR characterization of PNI severity remains challenging. Useful features indicative of high-grade PNI include bulbous enlargement, perineural fibrosis, muscle denervation changes, and nerve discontinuity.

Summary: There are many surgical approaches described to treat and prevent symptomatic neuromas, each of which has significant limitations. Here we describe the rationale and technical approach for a novel method that carries the promise of addressing some of these limitations.

Nerve sheath tumors occur as a heterogeneous group of neoplasms in patients with neurofibromatosis type 1 (NF1). The malignant form represents the most common cause of death in people with NF1, and even when benign, these tumors can result in significant disfigurement, neurologic dysfunction, and a range of profound symptoms. Lack of human tissue across the peripheral nerve tumors common in NF1 has been a major limitation in the development of new therapies. To address this unmet need, we have created an annotated collection of patient tumor samples, patient-derived cell lines, and patient-derived xenografts, and carried out high-throughput genomic and transcriptomic characterization to serve as a resource for further biologic and preclinical therapeutic studies. In this work, we release genomic and transcriptomic datasets comprised of 55 tumor samples derived from 23 individuals, complete with clinical annotation. All data are publicly available through the NF Data Portal and at http://synapse.org/jhubiobank., Measurement(s)gene expression • gene_variantTechnology Type(s)RNA sequencing • exome sequencing • DNA sequencingFactor Type(s)tumor typeSample Characteristic - OrganismHomo sapiens • Homo sapiens/Mus musculus xenograft Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12037599

The presence of Alternative lengthening of telomeres (ALT) and/or ATRX loss, as well as the role of other telomere abnormalities, have not been formally studied across the spectrum of NF1-associated solid tumors. Utilizing a telomere-specific FISH assay, we classified tumors as either ALT-positive or having long (without ALT), short, or normal telomere lengths. A total of 426 tumors from 256 NF1 patients were evaluated, as well as 99 MPNST tumor samples that were sporadic or of unknown NF1 status. In the NF1-glioma dataset, ALT was present in the majority of high-grade gliomas: 14 (of 23; 60%) in contrast to only 9 (of 47; 19%) low-grade gliomas (p = 0.0009). In the subset of ALT-negative glioma cases, telomere lengths were estimated and we observed 17 (57%) cases with normal, 12 (40%) cases with abnormally long, and only 1 (3%) case with short telomeres. In the NF1-associated malignant nerve sheath tumor (NF1-MPNST) set (n = 75), ALT was present in 9 (12%). In the subset of ALT-negative NF1-MPNST cases, telomeres were short in 9 (38%), normal in 14 (58%) and long in 1 (3%). In the glioma set, overall survival was significantly decreased for patients with ALT-positive tumors (p

Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are three clinically distinct tumor predisposition syndromes with a shared tendency to develop peripheral and central nervous system neoplasms. Disease expression and complications of NF1, NF2, and SWN are highly variable, necessitating a multidisciplinary approach to care in order to optimize outcomes. This review will discuss the imaging appearance of NF1, NF2, and SWN and highlight the important role that imaging plays in informing management decisions in people with tumors associated with these syndromes. Recent technological advances, including the role of both whole-body and localized imaging strategies, routine anatomic and advanced magnetic resonance (MR) imaging sequences such as diffusion-weighted imaging (DWI) with quantitative apparent diffusion coefficient (ADC) mapping, and metabolic imaging techniques (MR spectroscopy and positron emission testing) are discussed in the context of the diagnosis and management of people with NF1, NF2, and SWN based on the most up-to-date clinical imaging studies.

Proximal peripheral nerve injuries often result in poor functional outcomes, chiefly because of the long time period between injury and the reinnervation of distal targets, which leads to muscle and Schwann cell atrophy. The supercharged end-to-side (SETS) nerve transfer is a recent technical innovation that introduces donor axons distally into the side of an injured nerve to rapidly innervate and support end organs while allowing for additional reinnervation after a proximal repair at the injury site. However, the mechanisms by which donor axons grow within the recipient nerve, contribute to muscle function, and impact the regeneration of native recipient axons are poorly understood. This uncertainty has slowed the transfer’s clinical adoption. The primary objective of this article is to comprehensively review the mechanisms underpinning axonal regeneration and functional recovery after a SETS nerve transfer. A secondary objective is to report current clinical applications in the upper limb and their functional outcomes. The authors also propose directions for future research with the aim of maximizing the clinical utility of the SETS transfer for peripheral nerve surgeons and their patients.

Glomus tumors are rare mesenchymal neoplasms usually involving the dermis, typically found in a subungual location, and historically hypothesized to arise from cells of the glomus body, an arteriovenous shunt involved in temperature regulation.1,2 The majority of these tumors are benign, although some exhibit more aggressive biologic features and clinical behavior (malignant glomus tumor, or glomangiosarcoma). Others have an intermediate phenotype and are classified as glomus tumors of uncertain malignant potential (GT-UMP).3 Herein, we present a case of an 18-year-old patient with two glomus tumors involving the lateral and posterior cords of the right brachial plexus. The magnetic resonance (MR) imaging, intraoperative and histologic findings, therapeutic approach, and unique response to molecularly targeted therapy are discussed.

Background Peripheral nerve injury is often followed by a highly variable recovery process with respect to both rapidity and efficacy. Identifying post-nerve injury phenomena is key to assessing the merit and timing of surgery as well as to tracking nerve recovery postoperatively. Diffusion Tensor Imaging (DTI) has been investigated in the clinical and research settings as a noninvasive technique to both assess and monitor each patient's unique case of peripheral nerve damage. New method We identify a MRI-suitable marker for tracking the exact site of either nerve injury or coaptation following surgical repair to aid with DTI analysis. Results Due to artefact and disruption of tractography, silver wire and microvascular clips were not suitable markers. AxoGuard®, 4-0 vicryl suture, and 10-0 polyamide suture, although detectable, did not produce a signal easily distinguished from post-surgical changes. Silicone was easily identifiable and stable in both the acute and delayed time points, exhibited negligible impact on DTI parameters, and possessed geometry to prevent nerve strangulation. Comparison with existing method Prior studies have not assessed the efficacy of other markers nor have they assessed silicone for potential artefact with DTI parameter analysis. Furthermore, this work demonstrates the reliability and compatibility of silicone in the delayed postoperative time period and includes its unique imaging appearance on high-resolution 11.7 MRI. Conclusion Semi-cylindrical silicone tubing can be used as a safe, reliable, and readily available radiological marker to visualize and monitor a region of interest on a rodent’s peripheral nerve for aiding assessments with diffusion tensor imaging.

Interventional magnetic resonance (MR) neurography is a minimally invasive technique that affords targeting of small nerves in challenging areas of the human body for highly accurate nerve blocks and perineural injections. This cross-sectional technique uniquely combines high tissue contrast and high-spatial-resolution anatomic detail, which enables the precise identification and selective targeting of peripheral nerves, accurate needle guidance and navigation of the needle tip within the immediate vicinity of a nerve, as well as direct visualization of the injected drug for the assessment of appropriate drug distribution and documentation of the absence of spread to confounding nearby nerves.

OBJECTIVE. In this article, we will review the normal anatomy and imaging features of various neuromuscular abnormalities related to suprascapular neuropathy. CONCLUSION. Suprascapular neuropathy can be difficult to distinguish from rotator cuff pathology, plexopathy, and radiculopathy. Electrodiagnostic studies are considered the reference standard for diagnosis; however, high-resolution 3-T MR neurography (MRN) can play an important role. MRN enables direct visualization of the nerve and simultaneous assessment of the cervical spine, brachial plexus, and rotator cuff.

Organized and hosted by the Children's Tumor Foundation (CTF), the Neurofibromatosis (NF) conference is the premier annual gathering for clinicians and researchers interested in neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN). The 2016 edition constituted a blend of clinical and basic aspects of NF research that helped in clarifying different advances in the field. The incorporation of next generation sequencing is changing the way genetic diagnostics is performed for NF and related disorders, providing solutions to problems like genetic heterogeneity, overlapping clinical manifestations, or the presence of mosaicism. The transformation from plexiform neurofibroma (PNF) to malignant peripheral nerve sheath tumor (MPNST) is being clarified, along with new management and treatments for benign and premalignant tumors. Promising new cellular and in vivo models for understanding the musculoskeletal abnormalities in NF1, the development of NF2 or SWN associated schwannomas, and clarifying the cells that give rise to NF1-associated optic pathway glioma were presented. The interaction of neurofibromin and SPRED1 was described comprehensively, providing functional insight that will help in the interpretation of pathogenicity of certain missense variants identified in NF1 and Legius syndrome patients. Novel promising imaging techniques are being developed, as well as new integrative and holistic management models for patients that take into account psychological, social, and biological factors. Importantly, new therapeutic approaches for schwannomas, meningiomas, ependymomas, PNF, and MPNST are being pursued. This report highlights the major advances that were presented at the 2016 CTF NF conference.

Purpose To determine if 3-T magnetic resonance (MR) neurography-guided retroperitoneal genitofemoral nerve (GFN) blocks are safe and effective for the diagnosis of genitofemoral neuralgia. Materials and Methods Following institutional review board approval and informed consent, 26 subjects (16 men, 10 women; mean age, 42 years [range, 24-78 years]; mean body mass index, 28 kg/m2 [range, 20-35 kg/m2]) with intractable groin pain were included. By using a 3-T MR imaging system, intermediate-weighted turbo spin-echo pulse sequences, and MR-conditional needles, diagnostic MR neurography-guided GFN blocks were performed in the retroperitoneum. Outcome variables included technical success, procedure time, complications, and rates of positive and negative GFN blocks in association with therapeutic outcomes. For the assessment of a learning curve, Mann-Whitney test was used. P values ≤ .05 were considered to indicate a statistically significant difference. Results In 26 subjects, 30 retroperitoneal GFN blocks were performed. Twelve (40%) were performed with an anterior needle path, 12 (40%) with a lateral needle path, and six (20%) with a posterior needle path. GFN blocks were technically successful in 24 of 26 (92%) subjects, achieving appropriate scrotal anesthesia. No complications occurred. The time required for a GFN block was 40 minutes (range, 18-67 minutes). The rate of a successful GFN intervention after a positive GFN block was 88% (14 of 16). The rate of a successful intervention of an alternative target after a negative GFN block was 71% (five of seven). Conclusion Selective retroperitoneally directed MR neurography-guided GFN blocks are safe and effective with high technical success and positive effect on surgical decision making in patients with presumed genitofemoral neuralgia. © RSNA, 2017 Online supplemental material is available for this article.

OBJECTIVE. Sports-related peripheral nerve injuries are common among athletes and are often underrecognized because of symptom overlap with more usual sports-related bone, soft-tissue, and joint injuries. CONCLUSION. MRI plays an increasingly important role in the workup of peripheral nerve injuries and may reveal severe nerve abnormalities before they are diagnosed by electrodiagnostic testing or a clinical examination. Sport-specific peripheral nerve injuries and their MRI appearance will be discussed in this article.

BACKGROUND C5 palsy is a known cause of postoperative deltoid weakness. Prognostic variables affecting the incidence of the palsy have been poorly understood. OBJECTIVE To determine the incidence and perioperative characteristics/predictors of C5 palsy after anterior vs posterior operations. METHODS All patients undergoing C4-5 operations for degenerative conditions were retrospectively reviewed over 21 years. Anterior operations included an anterior cervical discectomy and fusion (ACDF) or a corpectomy, whereas posterior operations included laminectomy and fusion (± foraminotomies). RESULTS Of the total 1001 operations, in 49.0% anterior and 51.0% posterior cases, there was an overall C5 palsy incidence of 5.2% (52 cases): 1.6% and 8.6%, respectively (P < .001). Of the 99 corpectomies, the palsy incidence of 4.0% was not only higher than ACDFs (1.0%), but also followed an upward trend with increasing corpectomy levels (P = .009). Of the 69 posterior and 83 anterior C4-5 foraminotomies, the incidence of C5 palsy was statistically higher in the posterior (14.5%) vs anterior (2.4%) cohort (P = .01). Multiple logistical regression identified older age as the strongest predictor of C5 palsy in the anterior (P = .02) and C4-5 foraminotomy in the posterior (P = .06) cohort. This condition improved within 3 to 6 months in 75% of patients in the anterior and 88.6% in the posterior cohort after a mean follow-up of 14.4 and 27.6 months, respectively. CONCLUSION In one of the largest cohorts on C5 palsy, we found in anterior operations an increasing number of corpectomy levels had a higher incidence of C5 palsy; however, older age was the strongest predictor of C5 palsy. In posterior operations, C4-5 foraminotomy carried the strongest correlation.

About one half of malignant peripheral nerve sheath tumors (MPNST) have Neurofibromin 1 (NF1) mutations. NF1 is a tumor suppressor gene essential for negative regulation of RAS signaling. Survival for MPNST patients is poor and we sought to identify an effective combination therapy. Starting with the mTOR inhibitors rapamycin and everolimus, we screened for synergy in 542 FDA approved compounds using MPNST cells with a native NF1 loss in both alleles. We further analyzed the cell cycle and signal transduction. In vivo growth effects of the drug combination with local radiation therapy were assessed in MPNST xenografts. The synergistic combination of mTOR inhibitors with bortezomib yielded a reduction in MPNST cell proliferation. The combination of mTOR inhibitors and bortezomib also enhanced the anti-proliferative effect of radiation in vitro. In vivo, the combination of mTOR inhibitor (everolimus) and bortezomib with radiation therapy decreased tumor growth and proliferation, and augmented apoptosis. The combination of approved mTOR and proteasome inhibitors with radiation showed a significant reduction of tumor growth in an animal model and should be investigated and optimized further for MPNST therapy.

Introduction Compound nerve action potential recordings are often used intraoperatively to assist the surgeon in decision making on surgical approaches during nerve repair surgeries. The methods used clinically are based on surgical recordings (Robert et al., 2009). Although these methods are of great simplicity as handheld electrodes are applied to a nerve dissected and isolated from surrounding tissues, implementation of the methods in the clinical setting remains challenging. Here, we report findings from an experiment where similar recordings were made in nonhuman primate in order to improve our understanding and the performance of the methods. Methods Recordings were made from the median nerve at the upper arm of an adult female pigtail monkey under TIVA (pentobarbital) and full NMB (pancuronium). Core body temperature was maintained near 38 °C. Nerve action potentials were induced by constant current stimulation and recorded using laboratory equipment. IONM electrodes were used: triple and double hook electrodes (Cadwell) for stimulation and recording, respectively. Results Using the same recording configuration as in the clinical situation, we failed to record recognizable compound action potentials across a short conduction length of a nerve (3–4 cm) that was isolated and suspended from surrounding tissues as large stimulus artifacts obscured the neuronal signal. The stimulus artifacts were suppressed and the compound nerve action potential became unmasked after a saline-soaked gauze was placed underneath the nerve between the stimulating and recording electrodes to bridge the nerve and the surrounding tissues (i.e., ‘bridge grounding’). Furthermore, compound action potentials were of small amplitude when all prongs of the stimulation electrode were placed underneath the nerve. However, the potentials increased markedly in size with another modification, i.e. when the nerve was placed between the middle prong and the outer 2 prongs of the stimulation electrode (i.e., ‘sandwich stimulation’) after reshaping of the prongs. The recordings were made at room temperature (about 23 °C) without use of warm saline irrigation, at which the compound action potentials preserved good amplitudes but slowed in conduction, leading to a better separation of compound action potentials from stimulus artifacts. Conclusion We reversely translated the clinical methods of nerve compound action potential recording to a laboratory setting in order to better understand the factors affecting performance. We observed that compound nerve action potentials could be reliably recorded with IONM electrodes when 2 modifications, the ‘bridge grounding’ and ‘sandwich stimulation’, were made. Confirmation and additional experiments are underway to revisit the clinically used recording techniques in the laboratory setting.

Peripheral nerve surgery represents a broad field of pathologic conditions, medical specialties, and anatomic regions of the body. Anatomic understanding of hierarchical nerve structure and the peripheral nervous system aids diagnosis and management of nerve lesions. Many peripheral nerves coalesce into organized arrays, including the cervical, brachial, and lumbosacral plexuses, controlling motor and sensory functions of the trunk and extremities. Individual or groups of nerves may be affected by various pathologic conditions, including trauma, entrapment, tumor, or iatrogenic damage. Current research efforts focus on enhancing the peripheral nerve regenerative process by targeting Schwann cells, nerve growth factors, and nerve allografts.

Sclerotic (T2 dark) lesions of the spine are infrequent and, as a result, these are often missed or misdiagnosed. Plain films may not be always available during magnetic resonance imaging (MRI) readout. Knowledge of such lesions and their imaging appearances on MRI evaluation is essential for a reader. Additionally, a systematic approach is important to accurately diagnose these lesions. In this article we discuss the various causes of spinal sclerotic lesions, describe their MRI characteristics with relevant case examples, and outline a systematic approach to their evaluation.

Neurofibromatosis type 1 (NF1) is a neurocutaneous syndrome characterized by the development of multiple peripheral nerve sheath tumors, the majority of which are benign neurofibromas. However, malignant peripheral nerve sheath tumors (MPNSTs) occur with a 10 % lifetime risk in patients with NF1, often developing within a neurofibroma. When clinical suspicion for an MPNST arises, imaging with FDG PET and MRI is performed to characterize a peripheral tumor for potential malignancy. In this report, we describe a patient with NF-1 who had two peripheral tumors with similar features by PET, both suspicious for MPNST, but differing features by MRI, one of which was subsequently determined to be an MPNST and the second to be a schwannoma.

The authors report a vascular malformation mimicking a plexiform peripheral nerve sheath tumor. Three Tesla magnetic resonance neurography with high-resolution anatomic and advanced functional diffusion tensor imaging was helpful in evaluating full extent of the lesion and characterizing its internal architecture.