Neurosurgery and Manned Spaceflight.

There has been a renewed interest in manned spaceflight due to endeavors by private and government agencies. Publicized goals include manned trips to or colonization of Mars. These missions will likely be of long duration, exceeding existing records for human exposure to extra-terrestrial conditions. Participants will be exposed to microgravity, temperature extremes, and radiation, all of which may adversely affect their physiology. Moreover, pathological mechanisms may differ from those of a terrestrial nature. Known central nervous system (CNS) changes occurring in space include rises in intracranial pressure and spinal unloading. Intracranial pressure increases are thought to occur due to cephalad re-distribution of body fluids secondary to microgravity exposure. Spinal unloading in microgravity results in potential degenerative changes to the bony vertebrae, intervertebral discs, and supportive musculature. These phenomena are poorly understood. Trauma is of highest concern due to its potential to seriously incapacitate crewmembers and compromise missions. Traumatic pathology may also be exacerbated in the setting of altered CNS physiology. Though there are no documented instances of CNS pathologies arising in space, existing diagnostic and treatment capabilities will be limited relative to those on Earth. In instances where neurosurgical intervention is required in space, it is not known whether open or endoscopic approaches are feasible. It is obvious that prevention of trauma and CNS pathology should be emphasized. Further research into neurosurgical pathology, its diagnosis, and treatment in space are required should exploratory or colonization missions be attempted.

Promises and Perils of Artificial Intelligence in Neurosurgery.

Artificial intelligence (AI)-facilitated clinical automation is expected to become increasingly prevalent in the near future. AI techniques may permit rapid and detailed analysis of the large quantities of clinical data generated in modern healthcare settings, at a level that is otherwise impossible by humans. Subsequently, AI may enhance clinical practice by pushing the limits of diagnostics, clinical decision making, and prognostication. Moreover, if combined with surgical robotics and other surgical adjuncts such as image guidance, AI may find its way into the operating room and permit more accurate interventions, with fewer errors. Despite the considerable hype surrounding the impending medical AI revolution, little has been written about potential downsides to increasing clinical automation. These may include both direct and indirect consequences. Directly, faulty, inadequately trained, or poorly understood algorithms may produce erroneous results, which may have wide-scale impact. Indirectly, increasing use of automation may exacerbate de-skilling of human physicians due to over-reliance, poor understanding, overconfidence, and lack of necessary vigilance of an automated clinical workflow. Many of these negative phenomena have already been witnessed in other industries that have already undergone, or are undergoing "automation revolutions," namely commercial aviation and the automotive industry. This narrative review explores the potential benefits and consequences of the anticipated medical AI revolution from a neurosurgical perspective.

Thread common peroneal nerve release-a cadaveric validation study.

OBJECTIVE: To determine if the thread release technique can be applied to common peroneal nerve entrapment at the fibular neck. METHODS: The thread common peroneal nerve release was performed on 15 fresh frozen cadaveric lower extremity specimens. All procedures were performed under ultrasound guidance and immediately underwent post-procedural gross anatomic inspection for completeness of decompression and presence or absence of iatrogenic neurovascular injury. RESULTS: All 15 specimens demonstrated complete transection of the deep fascia of the peroneus longus overlying the common peroneal nerve. The transections extended to the bifurcation of the superficial peroneal and deep peroneal nerves. There was no evidence of any iatrogenic damage to the neurovascular bundle or adjacent tendons. The average operating time was less than 30 min. CONCLUSION: This cadaveric validation study demonstrates the accuracy of the thread common peroneal nerve release. Future pilot studies are warranted to ensure the safety of this procedure in the clinical setting.

Percutaneous cubital tunnel release with a dissection thread: a cadaveric study.

This cadaveric study tested the feasibility of decompressing the ulnar nerve across the elbow percutaneously with a commercially available surgical dissection thread, a guiding needle, hydrodissection and ultrasound guidance. We performed the procedure in 19 fresh-frozen cadaveric upper extremities. Subsequently, we did an anatomical dissection of the specimens to visualize the extent of ulnar nerve decompression and the extent of damage to surrounding structures. The cubital tunnel and deep across the medial elbow were completely transected leaving the ulnar nerve fully decompressed in all cases. There was no evidence of direct injury to the ulnar nerve or adjacent neurovascular structures. A prerequisite knowledge of sonographic anatomy and experience with interventional ultrasound is essential. Future clinical studies should evaluate this technique's safety and efficacy compared with conventional ones.

A cadaveric study using the ultra-minimally invasive thread transection technique to decompress the superficial peroneal nerve in the lower leg.

BACKGROUND: After successful applications of the ultra-minimally invasive thread transecting technique (Guo Technique) for both thread carpal tunnel release and thread trigger finger release, we hypothesized that this technique could be used for superficial peroneal nerve release in the lower leg by selective crural fasciectomy. This study is aimed at testing the operative feasibility of performing the thread superficial peroneal nerve release (TSPNR) procedure in cadavers. METHODS: The TSPNR procedure was performed on 15 fresh frozen cadaveric lower-extremity specimens under ultrasound guidance. All cadaveric specimens were dissected and visually assessed immediately after the procedures. RESULTS: All 15 legs demonstrated a complete transection of the crural fasciae along the course of the superficial peroneal nerve (SPN) including where it penetrated and traversed the crural fascia. There was no evidence of any iatrogenic damage to the neurovascular bundle or adjacent tendons. The average operating time was less than 20 min. CONCLUSION: This cadaveric study demonstrated that the technique of TSPNR was accurate, reliable, and feasible while causing no injury to adjacent neurovascular structures and avoiding having to make a skin incision. Further studies are warranted to verify the results of this study before implementing this new technique in the clinical setting.

Predictive value of a diagnostic block in focal nerve injury with neuropathic pain when surgery is considered.

OBJECT: In patients with focal nerve injury and neuropathic pain cutting the nerve to obtain permanent pain reduction can be considered. Surgery is indicated only if a diagnostic nerve block provides temporary pain relief. We evaluated the predictive value of a block on the outcome of surgery. METHODS: In total, three blocks were performed at two week intervals. Patients were blinded to injections containing lidocaine 1% and a placebo was included. Surgery was offered regardless of the effect of the blocks. Twenty-four patients received 72 blocks. Sixteen patients opted for surgery, 5 patients refrained from surgery, and in 3 the blocks provided permanent pain relief. The predictive ability of the block on the outcome of surgery was assessed by calculating the area under a Receiver Operating Characteristic curve (AUC). RESULTS: The AUC of the first lidocaine block was 0.35 with a 95% confidence interval from 0.077 to 0.62. At 95% confidence (two-sided), the AUC is less than 0.62, and hence the predictive ability of the block was poor. The outcome of the second lidocaine block and saline block did not change the conclusion of the first block. CONCLUSIONS: We conclude that the use of blocks to select patients for surgery should be critically appraised. PERSPECTIVE: A pain relieving response to one open block is currently considered mandatory before patients with focal nerve injury and neuropathic pain are offered surgery. Blinded blocks including a placebo show that responses for selection should be carefully interpreted because they may not be as predictive as generally presumed.

Intraoperative monitoring of neuromuscular function with soft, skin-mounted wireless devices.

Peripheral nerves are often vulnerable to damage during surgeries, with risks of significant pain, loss of motor function, and reduced quality of life for the patient. Intraoperative methods for monitoring nerve activity are effective, but conventional systems rely on bench-top data acquisition tools with hard-wired connections to electrode leads that must be placed percutaneously inside target muscle tissue. These approaches are time and skill intensive and therefore costly to an extent that precludes their use in many important scenarios. Here we report a soft, skin-mounted monitoring system that measures, stores, and wirelessly transmits electrical signals and physical movement associated with muscle activity, continuously and in real-time during neurosurgical procedures on the peripheral, spinal, and cranial nerves. Surface electromyography and motion measurements can be performed non-invasively in this manner on nearly any muscle location, thereby offering many important advantages in usability and cost, with signal fidelity that matches that of the current clinical standard of care for decision making. These results could significantly improve accessibility of intraoperative monitoring across a broad range of neurosurgical procedures, with associated enhancements in patient outcomes.

An update on addressing important peripheral nerve problems: challenges and potential solutions.

From time to time it is thoughtful and productive to review a medical field and reflect upon what are the major issues that need to be addressed and what is being done to do so. This review article is not meant to be all-inclusive but rather focuses on four evolving areas in the field of peripheral nerve disorders and treatments: (1) nerve surgery under ultrasound guidance using a new ultra-minimally invasive thread technique; (2) evolving magnetic resonance imaging (MRI) and ultrasound imaging techniques that are helping to both diagnose and treat a variety of peripheral nerve problems including entrapment neuropathies, traumatic nerve injuries, and masses arising from nerves; (3) promoting recovery after nerve injury using electrical stimulation; and (4) developing animal models to reproduce a severe nerve injury (neurotmetic grade in continuity) that requires a surgical intervention and repair. In each area we first describe the current challenges and then discuss new and emerging techniques and approaches. It is our hope that this article will bring added attention and resources to help better address peripheral nerve problems that remain a challenge for both patients and physicians.

Peripheral nerve diffusion tensor imaging as a measure of disease progression in ALS.

Clinical trial design in amyotrophic lateral sclerosis (ALS) remains hampered by a lack of reliable and sensitive biomarkers of disease progression. The present study evaluated peripheral nerve diffusion tensor imaging (DTI) as a surrogate marker of axonal degeneration in ALS. Longitudinal studies were undertaken in 21 ALS patients studied at 0 and 3 months, and 19 patients at 0, 3 and 6 months, with results compared to 13 age-matched controls. Imaging metrics were correlated across a range of functional assessments including amyotrophic lateral sclerosis functional rating scale revised (ALSFRS-R), lower limb muscle strength (Medical Research Council sum score, MRCSS-LL), compound muscle action potential amplitudes and motor unit number estimation (MUNE). Fractional anisotropy was reduced at baseline in ALS patients in the tibial (p < 0.05), and peroneal nerve (p < 0.05). Fractional anisotropy and axial diffusivity declined in the tibial nerve between baselines, 3- and 6-month scans (p < 0.01). From a functional perspective, ALSFRS-R correlated with fractional anisotropy values from tibial (R = 0.75, p < 0.001) and peroneal nerves (R = 0.52, p = 0.001). Similarly, peroneal nerve MUNE values correlated with fractional anisotropy values from the tibial (R = 0.48, p = 0.002) and peroneal nerve (R = 0.39, p = 0.01). There were correlations between the change in ALSFRS-R and tibial nerve axial diffusivity (R = 0.38, p = 0.02) and the change in MRCSS-LL and peroneal nerve fractional anisotropy (R = 0.44, p = 0.009). In conclusion, this study has demonstrated that some peripheral nerve DTI metrics are sensitive to axonal degeneration in ALS. Further, that DTI metrics correlated with measures of functional disability, strength and neurophysiological measures of lower motor neuron loss.

Correction: Whole Exome Sequencing of Growing and Non-Growing Cutaneous Neurofibromas from a Single Patient with Neurofibromatosis Type 1.

[This corrects the article DOI: 10.1371/journal.pone.0170348.].

Whole Exome Sequencing of Growing and Non-Growing Cutaneous Neurofibromas from a Single Patient with Neurofibromatosis Type 1.

The growth behaviors of cutaneous neurofibromas in patients with Neurofibromatosis type 1 are highly variable. The role of the germline NF1 mutation, somatic NF1 mutation and mutations at modifying loci, are poorly understood. We performed whole exome sequencing of three growing and three non-growing neurofibromas from a single individual to assess the role of acquired somatic mutations in neurofibroma growth behavior. 1-11 mutations were identified in each sample, including two deleterious NF1 mutations. No trends were present between the types of somatic mutations identified and growth behavior. Mutations in the HIPPO signaling pathway appeared to be overrepresented.

Epigenetic mechanisms drive the progression of neurofibromas to malignant peripheral nerve sheath tumors.

THINKING OUTSIDE THE BOX: The polycomb repressive complex 2 (PRC2) is a histone methyltransferase complex known to repress gene expression. There is a large body of experimental evidence that supports its role in promoting tumorigenicity by suppressing tumor suppressor genes. Here, we discuss the surprising findings that, in neurofibromas, it may have a completely different role as a tumor suppressor; mutations of PRC2 lead to conversion of benign neurofibromas into malignant peripheral nerve sheath tumors (MPNSTs) by de-repressing and thereby activating genes driving cell growth and development. These findings have potentially powerful clinical applications in both diagnosing and treating MPNSTs. HYPOTHESIS: PRC2 loss drives malignant transformation of neurofibromas.

Developing an algorithm for cost-effective, clinically judicious management of peripheral nerve tumors.

Peripheral nerve tumors such as neurofibromas and schwannomas have become increasingly identified secondary to improved imaging modalities including magnetic resonance neurogram and ultrasound. Given that a majority of these peripheral nerve tumors are benign lesions, it becomes important to determine appropriate management of such asymptomatic masses. We propose a normal cost-effective management paradigm for asymptomatic peripheral nerve neurofibromas and schwannomas that has been paired with economic analyses. Specifically, our management paradigm identifies patients who would benefit from surgery for asymptomatic peripheral nerve tumors, while providing cost-effective recommendations regarding clinical exams and serial imaging for such patients.

Peripheral nerve imaging.

Disorders of peripheral nerve have been traditionally diagnosed and monitored using clinical and electrodiagnostic approaches. The last two decades have seen rapid development of both magnetic resonance imaging (MRI) and ultrasound imaging of peripheral nerve, such that these imaging modalities are increasingly invaluable to the diagnosis of patients with peripheral nerve disorders. Peripheral nerve imaging provides information which is supplementary to clinical and electrodiagnostic diagnosis. Both MRI and ultrasound have particular benefits in specific clinical circumstances and can be considered as complementary techniques. These technologic developments in peripheral nerve imaging will usher in an era of multimodality assessment of peripheral nerve disorders, with clinical evaluations supported by anatomic information from imaging, and functional information from electrodiagnostic studies. Such a multimodality approach will improve the accuracy and efficiency of patient care.