The Evolving Classification of Meningiomas: Integration of Molecular Discoveries to Inform Patient Care.

Meningioma classification and treatment have evolved over the past eight decades. Since Bailey, Cushing, and Eisenhart's description of meningiomas in the 1920s and 1930s, there have been continual advances in clinical stratification by histopathology, radiography and, most recently, molecular profiling, to improve prognostication and predict response to therapy. Precise and accurate classification is essential to optimizing management for patients with meningioma, which involves surveillance imaging, surgery, primary or adjuvant radiotherapy, and consideration for clinical trials. Currently, the World Health Organization (WHO) grade, extent of resection (EOR), and patient characteristics are used to guide management. While these have demonstrated reliability, a substantial number of seemingly benign lesions recur, suggesting opportunities for improvement of risk stratification. Furthermore, the role of adjuvant radiotherapy for grade 1 and 2 meningioma remains controversial. Over the last decade, numerous studies investigating the molecular drivers of clinical aggressiveness have been reported, with the identification of molecular markers that carry clinical implications as well as biomarkers of radiotherapy response. Here, we review the historical context of current practices, highlight recent molecular discoveries, and discuss the challenges of translating these findings into clinical practice.

Utilizing Neuromodulation in the Treatment of Spinal Cord Injury: An Assessment of Clinical Trials from the National ClinicalTrials.gov Database.

OBJECTIVE: Spinal cord injury (SCI) is responsible for approximately 18,000 trauma cases each year in the United States, often resulting in debilitating motor and autonomic disability. Neuromodulation is a rapidly growing field of interest in the neurosurgical field and has additionally shown promise in the treatment of SCI. This review characterizes all clinical trials to date studying neuromodulation for the treatment of SCI. METHODS: The ClinicalTrials.gov database was queried using the search terms "neuromodulation" and "spinal cord injury" on ClinicalTrials.gov. Trials were excluded if they were not yet recruiting, suspended, terminated early, or of unknown status. RESULTS: In total, 33 clinical trials were included in this study. Of the 33 trials, 8 were completed and 1 had published results. Most trials studied deficits of motor function (60%) and bladder control (37%). Fourteen studies (42.4%) utilized transcutaneous spinal stimulation, 7 (21.2%) utilized epidural electrical stimulation, and 6 (18.2%) utilized tibial nerve stimulation. There was an uptrend of clinical trials studying SCI indexed on PubMed, which was comparable to the increased number of publications indexed overall (Pearson correlation, P < 0.001). Of these, only 1 study regarding home tibial nerve stimulation for neurogenic bladder had published data, which was performed with no adverse events. CONCLUSIONS: Neuromodulation in SCI studies currently assess transcutaneous spinal stimulation, epidural electrical stimulation, and tibial nerve stimulation. There is currently 1 completed study suggesting feasibility of home neuromodulation techniques without adverse events. The results of trials that will be completed in the next few years will help dictate the potential of neuromodulation as a treatment for SCI.

Diagnostic value of proximal cutaneous nerve biopsy in brachial and lumbosacral plexus pathologies.

BACKGROUND: Brachial and lumbosacral plexopathies can result from numerous non-traumatic etiologies, including those of inflammatory, autoimmune, or neoplastic origin, that often require nerve biopsy for diagnosis. The purpose of this study was to evaluate the diagnostic efficacy of medial antebrachial cutaneous nerve (MABC) and posterior femoral cutaneous nerve (PFCN) nerve biopsies in proximal brachial and lumbosacral plexus pathology. METHOD: Patients undergoing MABC or PFCN nerve biopsies at a single institution were reviewed. Patient demographics, clinical diagnosis, symptom duration, intraoperative findings, post-operative complications, and pathology results were recorded. Biopsy results were classified as diagnostic, inconclusive, or negative based on the final pathology. RESULTS: Thirty patients undergoing MABC biopsies in the proximal arm or axilla and five patients with PFCN biopsies in the thigh or buttock were included. MABC biopsies were diagnostic in 70% of cases overall and 85% diagnostic in cases where pre-operative MRI also demonstrated abnormalities in the MABC. PFCN biopsies were diagnostic in 60% of cases overall and in 100% of patients with abnormal pre-operative MRIs. There were no biopsy-related post-operative complications in either group. CONCLUSIONS: In diagnosing non-traumatic etiologies of brachial and lumbosacral plexopathies, proximal biopsies of the MABC and PFCN provide high diagnostic value with low donor morbidity.

PET imaging characteristics of neuromuscular choristoma and associated desmoid-type fibromatosis.

BACKGROUND: Neuromuscular choristoma (NMC) is a rare peripheral nerve lesion characterized by abnormal presence of muscle within nerve. Associated desmoid-type fibromatosis (NMC-DTF) often develops. We report 18F-fluorodeoxyglucose positron emission tomography (FDG PET) characteristics of NMC and NMC-DTF and propose that increased FDG activity within NMCs may be associated with subclinical NMC-DTF or NMC-DTF "precursor" tissue. METHODS: Our institutional database was searched for all NMC cases. Inclusion criteria were 1) confirmed diagnosis of NMC with or without biopsy, and 2) available PET and MRI studies. PET data included SUVmax and SUVmean of NMCs, contralateral limb normal skeletal muscle and unaffected nerves, and SUVmax of NMC-DTF if present. SUV values were compared using paired t-test. A p value of < 0.05 was considered statistically significant. RESULTS: Our cohort consisted of 9 patients with NMC, 8 cases involving sciatic nerve and 1 of brachial plexus. On PET imaging, all NMC-affected nerve segments showed significantly higher FDG uptake (SUVmax/mean) compared to both contralateral normal nerve and normal skeletal muscle (all P < 0.05). Similar to sporadic DTF, NMC-DTF was highly FDG-avid (average SUVmax of 4.2). SUVmax in NMC with or without concurrent NMC-DTF did not differ (p = 0.76). Within NMC-affected nerve segment, FDG activity was relatively higher in areas with low T1/T2 MR signal. CONCLUSION: All NMCs were more FDG avid compared to both normal skeletal muscle and contralateral unaffected nerve, arguing against the presence of heterotopic muscle in NMC as the source of FDG avidity. FDG avidity within NMC may reflect subclinical NMC-DTF or a precursor lesion, as NMC-DTF are highly FDG-avid, and the highest regions of FDG avidity in NMC occurred in regions with MR characteristics associated with NMC-DTF (i.e., lower T1/T2 signal). We believe that the integration of FDG PET with serial MR imaging in patient follow up will clarify its utility in both detection and surveillance of NMC-DTF.

Upper Extremity Neuropathies Following Severe COVID-19 Infection: A Multicenter Case Series.

OBJECTIVE: The purpose of the study is to examine presentation, injury patterns, and clinical course, for COVID-19-related peripheral nerve injury following mechanical ventilation. METHODS: A multicenter retrospective study of patients with COVID-19 complicated by acute respiratory distress syndrome (ARDS) that required mechanical ventilation was undertaken. Patient records were reviewed for intensive care unit and intubation characteristics, prone or lateral decubitus positioning, and the onset of neuropathy diagnosis. RESULTS: Between September 2020 and January 2022, 11 patients were diagnosed with peripheral neuropathy, including 9 with brachial plexopathy following COVID-19 infection. Each patient developed ARDS requiring mechanical ventilation for a median of 39 days. Six patients (54.5%) underwent prone positioning and 1 lateral decubitus. Neuropathies involved 5 brachial pan-plexopathies, 2 incomplete brachial plexopathies, 2 lower trunk plexopathies, 1 radial neuropathy, and 1 bilateral ulnar neuropathy. At a mean follow-up of 10.2 months, patients with brachial pan-plexopathies demonstrated signs of reinnervation proximally, and 1 resolved to a radial mononeuropathy; however, the majority have demonstrated minimal clinical improvements. CONCLUSIONS: Our series demonstrates that peripheral neuropathies and especially brachial plexopathies have occurred following mechanical ventilation for ARDS-related COVID-19 infections. Contrary to prior COVID-19 studies, only 54.5% of these patients underwent prone positioning. Aside from a traumatic disturbance of prone positioning, the increased incidence of neuropathy may involve an atraumatic effect of COVID-19 via direct invasion of nerves, autoantibody targeting of nervous tissue, or hypercoagulation-induced microthrombotic angiopathy.

The distribution of acquired peripheral nerve injuries associated with severe COVID-19 implicate a mechanism of entrapment neuropathy: a multicenter case series and clinical feasibility study of a wearable, wireless pressure sensor.

We diagnosed 66 peripheral nerve injuries in 34 patients who survived severe coronavirus disease 2019 (COVID-19). We combine this new data with published case series re-analyzed here (117 nerve injuries; 58 patients) to provide a comprehensive accounting of lesion sites. The most common are ulnar (25.1%), common fibular (15.8%), sciatic (13.1%), median (9.8%), brachial plexus (8.7%) and radial (8.2%) nerves at sites known to be vulnerable to mechanical loading. Protection of peripheral nerves should be prioritized in the care of COVID-19 patients. To this end, we report proof of concept data of the feasibility for a wearable, wireless pressure sensor to provide real time monitoring in the intensive care unit setting.

Presentation, management and outcome of surgically managed pediatric thoracic outlet syndrome.

PURPOSE: Thoracic outlet syndrome (TOS) is a rare disorder involving compression of the brachial plexus, subclavian artery, and subclavian vein. There is a paucity of data for this pathology's surgical treatment within pediatrics. The objective of this study is to explore the presentation, management, and outcome of pediatric TOS. METHODS: A retrospective chart review was conducted for 44 patients at a single institution undergoing surgery for TOS. Data was collected on demographics, pre- and postoperative factors, and outcomes. RESULTS: Forty-four patients underwent 50 surgeries (8 bilaterally). The average age was 15.5 years with 72% female. The most common symptoms were numbness (72%) and pain (66%), with a normal exam in 58%. The average symptom duration prior to surgery was 35.2 months. A supraclavicular approach was performed in all patients, with anterior scalene section (90%), rib resection (72%), neurolysis (92%), and intraoperative EMG (84%) commonly used. Two patients had a lymphatic leak. All patients reported subjective improvement of preoperative symptoms of numbness (26%), pain (22%), and weakness (6%). Differences between vTOS (n = 9) and nTOS (n = 35) included higher preop swelling (p < 0.012), decreased symptom duration (p < 0.022), higher venogram usage (p < 0.0030), and higher preoperative thrombolytics/angioplasty (p < 0.001) in vTOS compared to nTOS. A comparison of soft tissue and soft tissue with bone decompression did not reveal any outcome differences. CONCLUSION: Pediatric TOS benefits from a multidisciplinary approach, showing good outcomes in postoperative symptom resolution. In our cohort, a supraclavicular approach provided an effective window for decompression with a low complication rate.

Does complete regression of intraneural ganglion cysts occur without surgery?

PURPOSE: The dynamic nature of intraneural ganglion cysts, including spontaneous expansion and regression, has been described. However, whether these cysts can regress completely in the absence of surgical management has important therapeutic implications. Therefore, we aim to review the literature for cyst regression without surgical intervention. METHODS: We reviewed our database of 970 intraneural ganglion cysts in the literature to search for evidence of complete regression based on strict radiologic confirmation, either spontaneously, or after percutaneous cyst aspiration or steroid injection. RESULTS: We did not find any examples of complete regression without surgical treatment that met inclusion criteria. Spontaneous regression was reported in four cases; however, only two cases had follow-up imaging, both of which demonstrated residual cysts. Nineteen cases of percutaneous intervention were found in the literature, 13 of which reported clinical improvement following aspiration/steroid injection; however, only seven cases had available imaging. Only two cases reported complete resolution of cyst on MR imaging at follow-up, but reinterpretation found residual intraneural cyst in both cases. CONCLUSION: We believe that pathology (structural abnormalities and/or increased joint fluid) always exists at the joint origin of intraneural ganglion cysts which persist even with regression of the cyst. The persistence of a capsular abnormality or defect can lead to recurrence of the cyst in the future, and while imaging may show dramatic decreases in cyst size, truly focused assessment of images will show a tiny focus of persistent intraneural cyst at the joint origin. Thus, expectant management or percutaneous intervention may lead to regression, but not complete resolution, of intraneural ganglion cysts.

Anterior interosseous nerve neuropathy in a patient with spinal cord injury: case report and literature review.

INTRODUCTION: Entrapment neuropathies, typically carpal tunnel syndrome and ulnar neuropathy, frequently occur in patients with spinal cord injury (SCI). Upper limb impairments due to entrapment neuropathy can be particularly debilitating in this population. Anterior interosseous nerve (AIN) neuropathy has not been previously described in the SCI population. CASE PRESENTATION: A 27-year-old left-handed man with a history of C7 ASIA Impairment Scale B spinal cord injury five years prior presented to clinic with decreased left thumb function as well as thumb flexion. Workup including nerve conduction studies, electromyogram, ultrasonographic assessment, and magnetic resonance neurography was consistent with compressive AIN neuropathy. Surgical exploration and neurolysis was performed, with improvement of symptoms. DISCUSSION: Entrapment neuropathies should be carefully considered in the evaluation of patients with SCI with new motor deficits. We report a case of AIN neuropathy in a patient with SCI successfully treated with surgical decompression, and review the literature describing upper extremity entrapment neuropathies in this population. Surgical decompression is an effective option for treatment of AIN neuropathy in the setting of SCI, though further characterization of the optimal management strategy is needed.

Mass Deployment of Deep Neural Network: Real-Time Proof of Concept With Screening of Intracranial Hemorrhage Using an Open Data Set.

BACKGROUND: Intracranial hemorrhage (ICH) is considered an emergency that requires rapid medical or surgical management. Previous studies have used artificial intelligence to attempt to expedite the diagnosis of this pathology on neuroimaging. However, these studies have used local, institution-specific data for training of networks that limit deployment of across broader hospital networks or regions because of data biases. OBJECTIVE: To demonstrate the creation of a neural network based on an openly available imaging data tested on data from our institution demonstrating a high-efficacy, institution-agnostic network. METHODS: A data set was created from publicly available noncontrast computed tomography images of known ICH. These data were used to train a neural network using distinct windowing and augmentation. This network was then validated in 2 phases using cohort-based (phase 1) and longitudinal (phase 2) approaches. RESULTS: Our convolutional neural network was trained on 752 807 openly available slices, which included 112 762 slices containing intracranial hemorrhage. In phase 1, the final network performance for intracranial hemorrhage showed a receiver operating characteristic curve (AUC) of 0.99. At the inflection point, our model showed a sensitivity of 98% at a threshold specificity of 99%. In phase 2, we obtained an AUC of 0.98 after analysis of 726 scans with a negative predictive value of 99.70% (n = 726). CONCLUSION: We demonstrate an effective neural network trained on completely open data for screening ICH at an unrelated institution. This study demonstrates a proof of concept for screening networks for multiple sites while maintaining high efficacy.

First-Line Stent Retriever versus Direct Aspiration for Acute Basilar Artery Occlusions: A Systematic Review and Meta-analysis.

BACKGROUND: Mechanical thrombectomy (MT) for anterior circulation stroke has been proven to be highly effective. In comparison, MT for basilar artery occlusion (BAO) continues to lack definitive evidence of efficacy. The main MT modalities are stent retriever (SR) and direct aspiration (DA). Several studies have been published comparing the 2 approaches. OBJECTIVE: We sought to directly compare and synthesize safety and efficacy outcomes with SR versus DA for acute BAO. METHODS: A systematic review and meta-analysis was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. RESULTS: Overall, 8 studies comprising 693 patients with BAO were included (SR: 457; DA: 236). The SR group was associated with statistically significant lower odds of modified Thrombolysis in Cerebral Infarction (mTICI) 2b/3 (odds ratio [OR]: 0.54; 95% confidence interval [CI]: 0.31-0.94) and mTICI3 (OR: 0.47; 95% CI: 0.23-0.95) compared with DA. Favorable outcome rates were similar between the 2 groups (OR: 0.83; 95% CI: 0.60-1.16). The rates of symptomatic intracerebral hemorrhage (OR: 3.57; 95% CI: 0.75-16.95), subarachnoid hemorrhage (SAH) (OR: 4.71; 95% CI: 0.82-26.90), and vessel perforation (OR: 2.64; 95% CI: 0.43-16.33) were higher in the SR group, but statistical significance was not reached. The rates of 90-day mortality were similar between the 2 groups (OR: 1.07; 95% CI: 0.67-1.70). Procedure duration was significantly shorter when DA was used compared with SR (weighted mean difference: 26.10 minutes; 95% CI: 13.28-38.92). CONCLUSIONS: SR is associated with statistically significant lower odds of mTICI 2b/3 and mTICI 3 recanalization rates compared with DA. SR appears to be associated with a higher complication rate, but significance was not reached.

Perineural spread of peripheral neurolymphomatosis to the cauda equina.

OBJECTIVE: Neurolymphomatosis (NL) is a rare manifestation of lymphoma confined to the peripheral nervous system that is poorly understood. It can be found in the cauda equina, but extraspinal disease can be underappreciated. The authors describe how extraspinal NL progresses to the cauda equina by perineural spread and the implications of this on timely and safe diagnostic options. METHODS: The authors used the Mayo Clinic medical records database to find cases of cauda equina NL with sufficient imaging to characterize the lumbosacral plexus diagnosed from tissue biopsy. Demographics (sex, age), clinical data (initial symptoms, cerebrospinal fluid, evidence of CNS involvement, biopsy location, primary or secondary disease), and imaging findings were reviewed. RESULTS: Ten patients met inclusion and exclusion criteria, and only 2 of 10 patients presented with cauda equina symptoms at the time of biopsy, with 1 patient undergoing a cauda equina biopsy. Eight patients were diagnosed with diffuse large B-cell lymphoma, 1 with low-grade B-cell lymphoma, and 1 with mantle cell lymphoma. Isolated spinal nerve involvement was identified in 5 of 10 cases, providing compelling evidence regarding the pathophysiology of NL. The conus medullaris was not radiologically involved in any case. Lumbosacral plexus MRI was able to identify extraspinal disease and offered diagnostically useful biopsy targets. FDG PET/CT was relatively insensitive for detecting disease in the cauda equina but was helpful in identifying extraspinal NL. CONCLUSIONS: The authors propose that perineural spread of extraspinal NL to infiltrate the cauda equina occurs in two phases. 1) There is proximal and distal spread along a peripheral nerve, with eventual spread to anatomically connected nerves via junction and branch points. 2) The tumor cells enter the spinal canal through corresponding neural foramina and propagate along the spinal nerves composing the cauda equina. To diffusely infiltrate the cauda equina, a third phase occurs in which tumor cells can spread circumdurally to the opposite side of the spinal canal and enter contralateral nerve roots extending proximally and distally. This spread of disease can lead to diffuse bilateral spinal nerve disease without diffuse leptomeningeal spread. Recognition of this phasic mechanism can lead to identification of safer extraspinal biopsy targets that could allow for greater functional recovery after appropriate treatment.

Chiari malformation type 1 presenting as isolated unilateral foot drop with rapid recovery following posterior fossa decompression.

BACKGROUND: Chiari malformation (CM) type 1 is characterized by descent of the cerebellar tonsils resulting from crowding of the posterior fossa. In 30% of cases, it is associated with syringomyelia. When symptomatic, it may result in a classic constellation of symptoms. CASE PRESENTATION: Here we describe a case of a 16-year-old male who presented with isolated, unilateral foot drop due to CM type 1 and holosyrinx. This unique presentation is extremely rare, and we additionally present a review of all other reported cases in the literature. After undergoing posterior fossa decompression with C1 laminectomy and duraplasty, our patient made a complete neurological recovery within 2 weeks postoperatively and his MRI entire spine at 3 months postoperatively demonstrated a nearly complete resolution of the holosyrinx with significant decompression of the foramen magnum. CONCLUSION: This rare presentation highlights the importance of maintaining a broad differential, particularly in pediatric patients, and expediting the workup in order to offer a surgical decompression within 1-2 months of foot weakness to maximize the probability of a full neurological recovery.

Hamstring branches of the sciatic nerve as donors for neurotization of the superior gluteal nerve: A cadaveric feasibility study.

Although superior gluteal nerve (SGN) injury can have significant morbidity, to date, surgical strategies for its repair are scant in the literature. Specifically, neurotization options have not been explored. To address this deficiency in the literature, the current cadaveric feasibility study was performed. Via a transgluteal approach on 16 cadaveric sides, the proximal sciatic nerve and the entrance of the SGN into the gluteus medius and minimus were identified. Additionally, branches from the sciatic nerve to the hamstring muscles were traced proximally to confirm their position in relation to the sciatic nerve as a whole. These branches were cut at the level of the ischial tuberosity and teased away from the sciatic nerve proximally to the greater sciatic foramen and transferred superolateral to the SGN. The diameter of each nerve branch was measured as well as its available length for reaching the SGN. All branches of the sciatic nerve to the hamstring muscles arose from the anteromedial part of the nerve. The mean diameters of the branches to the semimembranosus, semitendinosus, and biceps femoris muscles were 2.1, 1.9, and 1.5 mm, respectively. The mean diameter of the SGN was 3.1 mm and the mean distance from this entrance point to the ischial spine was 7.2 cm. The mean length of the donor nerve was 8.5 cm. Based on our study, use of a tibial-innervated hamstring branch as a donor for nerve transfer to the SGN is feasible.

Utility of carbon fiber instrumentation in spinal oncology.

Spinal oncology has had many advancements often necessitating serial imaging for post-surgical treatment planning and close follow up. Traditional spinal instrumentation introduces artifact into MRI and CT imaging, which can reduce the efficacy of follow up imaging and treatment. Newly created carbon-fiber instrumentation can offer many advantages compared to traditional instrumentation while typically maintaining biomechanical stability. The utility of this new instrumentation continues to evolve as more surgeons utilize these materials, which can improve patient outcomes. We illustrate the utility of this new hardware technology through various patient examples.

Hemangioblastoma of the Peripheral Nervous System: A Critical Analysis of Its Rarity in Von Hippel-Lindau Disease.

Von Hippel-Lindau (VHL) disease is a multisystem disease cause by germline mutations of the VHL tumor suppressor gene. Hemangioblastomas are the most common manifestation of VHL disease and can occur in the central nervous system in up to 90% of these patients. By contrast, we found only one true case of a peripheral nervous system (PNS) hemangioblastoma in the setting of VHL. We explore the possible reasons behind the lack of PNS hemangioblastomas in VHL disease.

Advanced Materials in Wireless, Implantable Electrical Stimulators That Offer Rapid Rates of Bioresorption for Peripheral Axon Regeneration.

Injured peripheral nerves typically exhibit unsatisfactory and incomplete functional outcomes, and there are no clinically approved therapies for improving regeneration. Post-operative electrical stimulation (ES) increases axon regrowth, but practical challenges from the cost of extended operating room time to the risks and pitfalls associated with transcutaneous wire placement have prevented broad clinical adoption. This study presents a possible solution in the form of advanced bioresorbable materials for thin, flexible, wireless implant that provides precisely controlled ES of the injured nerve for a brief time in the immediate post-operative period. Afterward, rapid, complete and safe modes of bioresorption naturally and quickly eliminate all of the constituent materials in their entirety, without the need for surgical extraction. The unusually high rate of bioresorption follows from the use of a unique, bilayer enclosure that combines two distinct formulations of a biocompatible form of polyanhydride as an encapsulating structure, to accelerate the resorption of active components and confine fragments until complete resorption. Results from mouse models of tibial nerve transection with re-anastomosis indicate that this system offers levels of performance and efficacy that match those of conventional wired stimulators, but without the need to extend the operative period or to extract the device hardware.

Conception and design of novel lumbar drain insertion simulator.

Lumbar drain insertion is a common procedure that is performed by anaesthesiologists, radiologists and neurosurgeons that is generally taught through supervised learning that can place patients at risk. We describe in detail the creation and considerations of a novel lumbar drain simulator designed to allow learners to rehearse the complete lumbar drain insertion procedure from start to finish. A lumbar drain simulator was designed with the goal of simulating drain placement on a patient including identifying physical landmarks, sterile field preparation, technical steps of the procedure, troubleshooting and securing and connecting the drainage system. Emphasis was placed on simulating the structural components of the anatomic compartments encountered during needle insertion and accurate reproduction of the tactile aspects of the procedure. The simulator is able to reproduce the critical aspects of drain placement, allowing for learners to practice a complete lumbar drain placement from start to finish. A complete simulation of lumbar drain placement can be created that allows learners to practise all aspects of the lumbar drain procedure. Learners can rehearse all steps of the procedure allowing them to be more confident and facile with the procedure, which can lead to improved patient safety and satisfaction.