Flexible circumferential bioelectronics to enable 360-degree recording and stimulation of the spinal cord.

The spinal cord is crucial for transmitting motor and sensory information between the brain and peripheral systems. Spinal cord injuries can lead to severe consequences, including paralysis and autonomic dysfunction. We introduce thin-film, flexible electronics for circumferential interfacing with the spinal cord. This method enables simultaneous recording and stimulation of dorsal, lateral, and ventral tracts with a single device. Our findings include successful motor and sensory signal capture and elicitation in anesthetized rats, a proof-of-concept closed-loop system for bridging complete spinal cord injuries, and device safety verification in freely moving rodents. Moreover, we demonstrate potential for human application through a cadaver model. This method sees a clear route to the clinic by using materials and surgical practices that mitigate risk during implantation and preserve cord integrity.

The paraneurium and the tumefactive appearance of peripheral nerve neurolymphomatosis: illustrative case.

BACKGROUND: Peripheral neurolymphomatosis (NL) is an often-misdiagnosed condition characterized by lymphomatous infiltration within the peripheral nerves. Its rarity and complexity frequently result in delayed diagnosis and suboptimal patient outcomes. This study aims to elucidate the role of the paraneurium (circumneurium) in NL, emphasizing its diagnostic and therapeutic significance. OBSERVATIONS: A 72-year-old man presented with lesions on his right lower eyelid. Initial diagnostics were inconclusive until an excisional biopsy confirmed extranodal marginal zone lymphoma. Following a complete metabolic response to rituximab treatment, the patient relapsed 14 months later with progressive lymphoma and bilateral sciatic nerve involvement, as confirmed by positron emission tomography-computed tomography and magnetic resonance imaging. LESSONS: This paper underscores the critical role of the paraneurium in NL, enhancing understanding of its pathophysiology. Integrating advanced imaging techniques have proved essential in accurately identifying neurolymphomatous involvement within the paraneurium. This study paves the way for more effective management strategies in NL and similar conditions, focusing on improving patient care and outcomes.

Electrochemically actuated microelectrodes for minimally invasive peripheral nerve interfaces.

Electrode arrays that interface with peripheral nerves are used in the diagnosis and treatment of neurological disorders; however, they require complex placement surgeries that carry a high risk of nerve injury. Here we leverage recent advances in soft robotic actuators and flexible electronics to develop highly conformable nerve cuffs that combine electrochemically driven conducting-polymer-based soft actuators with low-impedance microelectrodes. Driven with applied voltages as small as a few hundreds of millivolts, these cuffs allow active grasping or wrapping around delicate nerves. We validate this technology using in vivo rat models, showing that the cuffs form and maintain a self-closing and reliable bioelectronic interface with the sciatic nerve of rats without the use of surgical sutures or glues. This seamless integration of soft electrochemical actuators with neurotechnology offers a path towards minimally invasive intraoperative monitoring of nerve activity and high-quality bioelectronic interfaces.

Regenerative capacity of neural tissue scales with changes in tissue mechanics post injury.

Spinal cord injuries have devastating consequences for humans, as mammalian neurons of the central nervous system (CNS) cannot regenerate. In the peripheral nervous system (PNS), however, neurons may regenerate to restore lost function following injury. While mammalian CNS tissue softens after injury, how PNS tissue mechanics changes in response to mechanical trauma is currently poorly understood. Here we characterised mechanical rat nerve tissue properties before and after in vivo crush and transection injuries using atomic force microscopy-based indentation measurements. Unlike CNS tissue, PNS tissue significantly stiffened after both types of tissue damage. This nerve tissue stiffening strongly correlated with an increase in collagen I levels. Schwann cells, which crucially support PNS regeneration, became more motile and proliferative on stiffer substrates in vitro, suggesting that changes in tissue stiffness may play a key role in facilitating or impeding nervous system regeneration.

Functional neurological restoration of amputated peripheral nerve using biohybrid regenerative bioelectronics.

The development of neural interfaces with superior biocompatibility and improved tissue integration is vital for treating and restoring neurological functions in the nervous system. A critical factor is to increase the resolution for mapping neuronal inputs onto implants. For this purpose, we have developed a new category of neural interface comprising induced pluripotent stem cell (iPSC)-derived myocytes as biological targets for peripheral nerve inputs that are grafted onto a flexible electrode arrays. We show long-term survival and functional integration of a biohybrid device carrying human iPSC-derived cells with the forearm nerve bundle of freely moving rats, following 4 weeks of implantation. By improving the tissue-electronics interface with an intermediate cell layer, we have demonstrated enhanced resolution and electrical recording in vivo as a first step toward restorative therapies using regenerative bioelectronics.

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

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

3D Bioelectronics with a Remodellable Matrix for Long-Term Tissue Integration and Recording.

Bioelectronics hold the key for understanding and treating disease. However, achieving stable, long-term interfaces between electronics and the body remains a challenge. Implantation of a bioelectronic device typically initiates a foreign body response, which can limit long-term recording and stimulation efficacy. Techniques from regenerative medicine have shown a high propensity for promoting integration of implants with surrounding tissue, but these implants lack the capabilities for the sophisticated recording and actuation afforded by electronics. Combining these two fields can achieve the best of both worlds. Here, the construction of a hybrid implant system for creating long-term interfaces with tissue is shown. Implants are created by combining a microelectrode array with a bioresorbable and remodellable gel. These implants are shown to produce a minimal foreign body response when placed into musculature, allowing one to record long-term electromyographic signals with high spatial resolution. This device platform drives the possibility for a new generation of implantable electronics for long-term interfacing.

X-Ray Markers for Thin Film Implants.

Implantable electronic medical devices are used in functional mapping of the brain before surgery and to deliver neuromodulation for the treatment of neurological and neuropsychiatric disorders. Their electrode arrays are assembled by hand, and this leads to bulky form factors with limited flexibility and low electrode counts. Thin film implants, made using microfabrication techniques, are emerging as an attractive alternative, as they offer dramatically improved conformability and enable high density recording and stimulation. A major limitation of these devices, however, is that they are invisible to fluoroscopy, the most common method used to monitor the insertion of implantable electrodes. Here, the development of mechanically flexible X-ray markers using bismuth- and barium-infused elastomers is reported. Their X-ray attenuation properties in human cadavers are explored and it is shown that they are biocompatible in cell cultures. It is further shown that they do not distort magnetic resonance imaging images and their integration with thin film implants is demonstrated. This work removes a key barrier for the adoption of thin film implants in brain mapping and in neuromodulation.

Hybrid fabrication of multimodal intracranial implants for electrophysiology and local drug delivery.

New fabrication approaches for mechanically flexible implants hold the key to advancing the applications of neuroengineering in fundamental neuroscience and clinic. By combining the high precision of thin film microfabrication with the versatility of additive manufacturing, we demonstrate a straight-forward approach for the prototyping of intracranial implants with electrode arrays and microfluidic channels. We show that the implant can modulate neuronal activity in the hippocampus through localized drug delivery, while simultaneously recording brain activity by its electrodes. Moreover, good implant stability and minimal tissue response are seen one-week post-implantation. Our work shows the potential of hybrid fabrication combining different manufacturing techniques in neurotechnology and paves the way for a new approach to the development of multimodal implants.

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

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

Spinal cord bioelectronic interfaces: opportunities in neural recording and clinical challenges.

Bioelectronic stimulation of the spinal cord has demonstrated significant progress in the restoration of motor function in spinal cord injury (SCI). The proximal, uninjured spinal cord presents a viable target for the recording and generation of control signals to drive targeted stimulation. Signals have been directly recorded from the spinal cord in behaving animals and correlated with limb kinematics. Advances in flexible materials, electrode impedance and signal analysis will allow spinal cord recording (SCR) to be used in next-generation neuroprosthetics. In this review, we summarize the technological advances enabling progress in SCR and describe systematically the clinical challenges facing spinal cord bioelectronic interfaces and potential solutions, from device manufacture, surgical implantation to chronic effects of foreign body reaction and stress-strain mismatches between electrodes and neural tissue. Finally, we establish our vision of bi-directional closed-loop spinal cord bioelectronic bypass interfaces that enable the communication of disrupted sensory signals and restoration of motor function in SCI.

Prevention of the foreign body response to implantable medical devices by inflammasome inhibition.

SignificanceImplantable electronic medical devices (IEMDs) are used for some clinical applications, representing an exciting prospect for the transformative treatment of intractable conditions such Parkinson's disease, deafness, and paralysis. The use of IEMDs is limited at the moment because, over time, a foreign body reaction (FBR) develops at the device-neural interface such that ultimately the IEMD fails and needs to be removed. Here, we show that macrophage nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activity drives the FBR in a nerve injury model yet integration of an NLRP3 inhibitor into the device prevents FBR while allowing full healing of damaged neural tissue to occur.

Far Lateral Approaches: C1 Meningioma With Vertebral Artery Involvement: 3-Dimensional Operative Video.

Tumors around the cervicomedullary junction are rare and constitute 5% of spinal tumors and 1% of cranial tumors. The approach to these lesions is difficult because of the close proximity of the medulla and cervical spinal cord, lower cranial nerves, and vertebral artery (VA) as well as the complex articulation between occipital condyle, C1 and C2. Cervicomedullary junction meningiomas are commonly classified based on their origin in relation to the dentate ligament, but the relationship to the VA typically plays an important role in deciding the surgical approach. For lesions located dorsal to the dentate ligament and not involving the VA, a midline approach is typically sufficient. However, when the VA is involved a far lateral approach is preferred as it offers better access to the V4 segment. We describe a case of a 55-yr-old man who presented with accessory nerve palsy and mild upper motor neuron signs and was found to have a C1 meningioma encasing and narrowing the VA at the V3/V4 segment. Informed consent was obtained. The patient was treated with a right far lateral approach with limited condylectomy to gain access to the V4 segment. We described the steps used for safe resection of the tumor around the VA from distal to proximal. We demonstrate the relationship of the tumor to the VA and the need to completely skeletonize the VA to achieve a gross total resection. We supplement the discussion with a 3D surgical video.

Far Lateral Approaches: Far Lateral Approach With Minimal Condylectomy for C2 Schwannoma: 3-Dimensional Operative Video.

Upper cervical schwannomas are rare lesions and together with meningiomas constitute around 5% of spinal tumors. The approach to these lesions is difficult because of the close proximity of the medulla and cervical spinal cord, lower cranial nerves, and the vertebral artery. Schwannomas in the upper cervical area typically arise from the dorsal roots and are located posterior to the dentate ligament. Nevertheless, a far lateral approach is often required for these lesions because of their lateral extent through the neural foramen and the proximity of both the V3 and V4 segments of the vertebral artery. With these lesions, an extensive condylectomy is rarely required. We present a case of a 40-yr-old woman who presented with an 8-mo history of deteriorating mobility and feeling of heaviness in the lower limbs with a further acute deterioration 1 wk before admission. She had a dissociated sensory loss and myelopathy in keeping with a partial hemicord syndrome. Imaging revealed a right-sided C2 intradural lesion extending through the C2 foramen in keeping with a C2 schwannoma. The patient was counseled on the treatment options, and informed consent for surgery was obtained. We describe a right-sided far lateral approach with minimal condylectomy for gross total resection of this lesion. We demonstrate the relationship of the tumor with the C2 nerve root, the spinal accessory nerve, and the cervical cord. We supplement the discussion with a 3D surgical video.

Far Lateral Approaches: Dural Arteriovenous Fistulae at the Hypoglossal Canal: 3-Dimensional Operative Video.

Cognard type V dural arteriovenous fistulae (dAVF) are typically located at the foramen magnum. Their presentation often mimics that of cervical myelopathy, and they can be easily misdiagnosed even if spinal vascular imaging is undertaken. Treatment typically involves endovascular embolization or surgery when embolization is not possible. We describe a case of a 67-yr-old man who presented with progressive symptoms of cervical myelopathy with a significant reduced ambulation and upper motor neuron signs. Imaging disclosed upper cervical cord edema, and angiography confirmed a Cognard type V dAVF with drainage into the perimedullary and spinal venous system. The dAVF was supplied by the hypoglossal division of the ascending pharyngeal artery. Endovascular treatment was believed to pose a risk of ischemic injury to the hypoglossal nerve, and therefore, surgery was offered. Informed consent was obtained. A far lateral approach was used to access the fistulous point. We describe the relevant vascular anatomy and the benefits of the far lateral approach for this lesion. We also demonstrate a tailored inferior condylectomy to gain access to the intracranial part of the hypoglossal canal, where the draining vein is expected to be found. We supplement the discussion with a 3D surgical video.

Surgical Resection of an Arteriovenous Malformation of the Orbital Surface of the Frontal Lobe with Olfactory Tract Preservation: 2-Dimensional Operative Video.

Medial orbitofrontal area arteriovenous malformations (AVMs) are located in the noneloquent cortex and typically drain superficially into Sylvian veins or the superior sagittal sinus, making them favorable for surgical treatment. However, while typically supplied by pial/cortical branches of the anterior cerebral artery (ACA), they can incorporate the recurrent artery of Heubner and other ACA perforators on their way to the anterior perforated substance located just posterior. We present a case of a 30-year-old female admitted with sudden collapse and intraventricular hemorrhage from a ruptured medial orbitofrontal area AVM. She was admitted to the intensive care unit and an external ventricular drain was placed to treat acute hydrocephalus. Catheter angiography demonstrated an AVM located just anteromedial to the termination of the internal carotid artery with a compact nidus and an associated intranidal flow aneurysm. Arterial supply originated from the orbitofrontal artery off the ACA, with medial lenticulostriates seen coursing past the nidus. Additional supply from the recurrent artery of Heubner could not be excluded. However, a hypodensity in the inferior frontal lobe seen on the presentation computed tomography scan was suggestive of a prior orbitofrontal infarct and thus cortical, rather than perforator, supply. In our practice, treatment of ruptured AVMs is dictated by the patients' clinical recovery and associated high-risk features (e.g., flow aneurysms). In this case, despite the presence of a flow aneurysm, treatment was delayed 18 days due to slow neurologic recovery and family preference. The patient remained in the intensive care unit under close neurologic observation. She was extubated on day 10, and the external ventricular drain was removed on day 12 after confirming resolution of intraventricular hemorrhage. Preoperatively the patient recovered to a Glasgow Coma Scale score of 15. Risks of treatment were discussed, and informed consent was obtained. The patient was treated using a standard pterional craniotomy. We describe the anatomic location of the lesion in the medial orbitofrontal area, the relationship to the olfactory tract and olfactory stria. We demonstrate olfactory tract dissection from its arachnoid cistern between the orbitofrontal lobe and gyrus rectus in order to access the lesion. Indocyanine green angiography is used to help surgical dissection and for quality control at the end of the procedure. We do not perform intraoperative angiography routinely; however, it can be a useful adjunct in deep and/or eloquent locations, which are difficult to image using videoangiography. Nevertheless, in the absence of intraoperative angiography close dissection directly over the nidus on the eloquent side ensures preservation of functional brain. We describe the microsurgical techniques of surgical treatment of AVMs, in particular the "cone" dissection technique of the AVM in order to allow identification of all feeding vessels and tracing "en passant" vessels from proximal to distal, as well as the use of intraoperative videoangiography to elucidate the nidus morphology and immediate postoperative quality control (Video 1, available at https://drive.google.com/file/d/1IXuLg84MwyMek1_Z1f1n7qssLThimvdx/view?usp=sharing).

Longitudinal Changes in Size of Conservatively Managed Flow-Related Aneurysms Associated with Brain Arteriovenous Malformations.

BACKGROUND: Flow aneurysms (FAs) associated with brain arteriovenous malformations (AVMs) are thought to arise from increased hemodynamic stress due to high-flow shunting. This study aims to describe the changes in conservatively managed FAs after successful AVM treatment. METHODS: Patients with symptomatic AVMs and associated FAs who underwent successful treatment of the AVM between 2008 and 2017 were included. FA dimensions were measured on surveillance angiography to assess longitudinal changes. RESULTS: Thirty-two patients were identified with 48 FAs. Sixteen (33%) FAs were treated endovascularly; 18 (38%) FAs were treated surgically; and 14 (29%) FAs (11 patients) were monitored. FAs demonstrated a decrease in size from 5.0 mm to 3.8 mm (24%; P = 0.016) and 4.9 mm to 3.6 mm (27%; P = 0.013) in height and width, respectively, over a median 35 months. However, on subgroup analysis, only class IIb aneurysms demonstrated a significant decrease in size (51% reduction in largest diameter, P = 0.046) and only 3 FAs (21%) resolved. There were no hemorrhages observed during follow-up. CONCLUSIONS: While conservatively managed FAs demonstrated a reduction in size after the culprit AVM was treated, this was only significant in FAs located close to an AVM nidus (class IIb). There were no hemorrhages during the median 35 months' follow-up; however, long-term data are lacking. Our data support close observation of all conservatively managed aneurysms and a tailored approach based on the proximity to the nidus and observed changes in size.

Large Animal Studies to Reduce the Foreign Body Reaction in Brain-Computer Interfaces: A Systematic Review.

Brain-computer interfaces (BCI) are reliant on the interface between electrodes and neurons to function. The foreign body reaction (FBR) that occurs in response to electrodes in the brain alters this interface and may pollute detected signals, ultimately impeding BCI function. The size of the FBR is influenced by several key factors explored in this review; namely, (a) the size of the animal tested, (b) anatomical location of the BCI, (c) the electrode morphology and coating, (d) the mechanics of electrode insertion, and (e) pharmacological modification (e.g., drug eluting electrodes). Trialing methods to reduce FBR in vivo, particularly in large models, is important to enable further translation in humans, and we systematically reviewed the literature to this effect. The OVID, MEDLINE, EMBASE, SCOPUS and Scholar databases were searched. Compiled results were analysed qualitatively. Out of 8388 yielded articles, 13 were included for analysis, with most excluded studies experimenting on murine models. Cats, rabbits, and a variety of breeds of minipig/marmoset were trialed. On average, over 30% reduction in inflammatory cells of FBR on post mortem histology was noted across intervention groups. Similar strategies to those used in rodent models, including tip modification and flexible and sinusoidal electrode configurations, all produced good effects in histology; however, a notable absence of trials examining the effect on BCI end-function was noted. Future studies should assess whether the reduction in FBR correlates to an improvement in the functional effect of the intended BCI.