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

Barone, Damiano G / Kendziora, Ryan W / Broski, Stephen M / Schembri Wismayer, David J / Spinner, Robert J

Journal of neurosurgery. Case lessons

2024 Volume 7, Issue 17

Abstract: 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. ... ...

Abstract	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.
Language	English
Publishing date	2024-04-22
Publishing country	United States
Document type	Journal Article
ISSN	2694-1902
ISSN (online)	2694-1902
DOI	10.3171/CASE24125
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Article ; Online: Epidermal electrophysiology at scale.

Barone, Damiano G / Malliaras, George G

Nature biomedical engineering

2019 Volume 3, Issue 3, Page(s) 165–166

MeSH term(s)	Cognition ; Electrophysiology ; Magnetic Resonance Imaging ; Skin
Language	English
Publishing date	2019-04-04
Publishing country	England
Document type	Journal Article ; Comment
ISSN	2157-846X
ISSN (online)	2157-846X
DOI	10.1038/s41551-019-0365-8
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Article ; Online: Spinal cord bioelectronic interfaces: opportunities in neural recording and clinical challenges.

Jiang, Lei / Woodington, Ben / Carnicer-Lombarte, Alejandro / Malliaras, George / Barone, Damiano G

Journal of neural engineering

2022 Volume 19, Issue 2

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Animals ; Biomechanical Phenomena ; Electrodes ; Spinal Cord/physiology ; Spinal Cord Injuries/therapy
Language	English
Publishing date	2022-04-14
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2170901-4
ISSN	1741-2552 ; 1741-2560
ISSN (online)	1741-2552
ISSN	1741-2560
DOI	10.1088/1741-2552/ac605f
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Zs.A 6071: Show issues

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Article ; Online: Regenerative capacity of neural tissue scales with changes in tissue mechanics post injury.

Carnicer-Lombarte, Alejandro / Barone, Damiano G / Wronowski, Filip / Malliaras, George G / Fawcett, James W / Franze, Kristian

Biomaterials

2023 Volume 303, Page(s) 122393

Abstract: 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. ... ...

Abstract	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.
MeSH term(s)	Humans ; Rats ; Animals ; Central Nervous System ; Schwann Cells/physiology ; Neurons ; Nerve Tissue ; Spinal Cord Injuries ; Nerve Regeneration/physiology ; Axons/physiology ; Mammals
Language	English
Publishing date	2023-11-09
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603079-8
ISSN	1878-5905 ; 0142-9612
ISSN (online)	1878-5905
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2023.122393
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Zs.B 2371: Show issues

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

Woodington, Ben J / Lei, Jiang / Carnicer-Lombarte, Alejandro / Güemes-González, Amparo / Naegele, Tobias E / Hilton, Sam / El-Hadwe, Salim / Trivedi, Rikin A / Malliaras, George G / Barone, Damiano G

Science advances

2024 Volume 10, Issue 19, Page(s) eadl1230

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Animals ; Spinal Cord/physiology ; Rats ; Spinal Cord Injuries/therapy ; Spinal Cord Injuries/physiopathology ; Humans ; Electric Stimulation/methods ; Electrodes, Implanted
Language	English
Publishing date	2024-05-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adl1230
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Article ; Online: Electrochemically actuated microelectrodes for minimally invasive peripheral nerve interfaces.

Dong, Chaoqun / Carnicer-Lombarte, Alejandro / Bonafè, Filippo / Huang, Botian / Middya, Sagnik / Jin, Amy / Tao, Xudong / Han, Sanggil / Bance, Manohar / Barone, Damiano G / Fraboni, Beatrice / Malliaras, George G

Nature materials

2024

Abstract: 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 ... ...

Abstract	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.
Language	English
Publishing date	2024-04-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2088679-2
ISSN	1476-4660 ; 1476-1122
ISSN (online)	1476-4660
ISSN	1476-1122
DOI	10.1038/s41563-024-01886-0
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Article: Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics.

Carnicer-Lombarte, Alejandro / Chen, Shao-Tuan / Malliaras, George G / Barone, Damiano G

Frontiers in bioengineering and biotechnology

2021 Volume 9, Page(s) 622524

Abstract: The implantation of any foreign material into the body leads to the development of an inflammatory and fibrotic process-the foreign body reaction (FBR). Upon implantation into a tissue, cells of the immune system become attracted to the foreign material ... ...

Abstract	The implantation of any foreign material into the body leads to the development of an inflammatory and fibrotic process-the foreign body reaction (FBR). Upon implantation into a tissue, cells of the immune system become attracted to the foreign material and attempt to degrade it. If this degradation fails, fibroblasts envelop the material and form a physical barrier to isolate it from the rest of the body. Long-term implantation of medical devices faces a great challenge presented by FBR, as the cellular response disrupts the interface between implant and its target tissue. This is particularly true for nerve neuroprosthetic implants-devices implanted into nerves to address conditions such as sensory loss, muscle paralysis, chronic pain, and epilepsy. Nerve neuroprosthetics rely on tight interfacing between nerve tissue and electrodes to detect the tiny electrical signals carried by axons, and/or electrically stimulate small subsets of axons within a nerve. Moreover, as advances in microfabrication drive the field to increasingly miniaturized nerve implants, the need for a stable, intimate implant-tissue interface is likely to quickly become a limiting factor for the development of new neuroprosthetic implant technologies. Here, we provide an overview of the material-cell interactions leading to the development of FBR. We review current nerve neuroprosthetic technologies (cuff, penetrating, and regenerative interfaces) and how long-term function of these is limited by FBR. Finally, we discuss how material properties (such as stiffness and size), pharmacological therapies, or use of biodegradable materials may be exploited to minimize FBR to nerve neuroprosthetic implants and improve their long-term stability.
Language	English
Publishing date	2021-04-15
Publishing country	Switzerland
Document type	Systematic Review
ZDB-ID	2719493-0
ISSN	2296-4185
ISSN	2296-4185
DOI	10.3389/fbioe.2021.622524
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Article ; Online: Far Lateral Approaches: Far Lateral Approach With Minimal Condylectomy for C2 Schwannoma: 3-Dimensional Operative Video.

Budohoski, Karol P / Barone, Damiano G / Kirollos, Ramez W / Santarius, Thomas / Trivedi, Rikin A

Operative neurosurgery (Hagerstown, Md.)

2021 Volume 22, Issue 1, Page(s) e49

Abstract: 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 ... ...

Abstract	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.
Language	English
Publishing date	2021-12-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	2767575-0
ISSN	2332-4260 ; 2332-4252
ISSN (online)	2332-4260
ISSN	2332-4252
DOI	10.1227/ONS.0000000000000032
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Zs.A 1424 -ON-: Show issues

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Article ; Online: Prostheses as extensions of the body: Progress and challenges.

Niedernhuber, Maria / Barone, Damiano G / Lenggenhager, Bigna

Neuroscience and biobehavioral reviews

2018 Volume 92, Page(s) 1–6

Abstract: Recent years have seen a surge of interest in the incorporation of artificial limbs. This research promises to provide individuals with sensorimotor disorders such as amputations with prostheses which feel like their own body part. While neuroscience ... ...

Abstract	Recent years have seen a surge of interest in the incorporation of artificial limbs. This research promises to provide individuals with sensorimotor disorders such as amputations with prostheses which feel like their own body part. While neuroscience made a leap towards uncovering the basic neurocognitive mechanisms of bodily self-consciousness, the development of incorporated prosthetic limbs still faces substantial challenges in basic neuroscience and in clinical reality. Here we critically examine recent findings on prosthesis incorporation to aid patient rehabilitation in the context of advances in cognitive and applied neuroscience as well as technology. To this end, we integrate results from fundamental and clinical neuropsychological research to outline how several crucial milestones will have to be passed to achieve the self-attribution of prostheses to one's own body. We further discuss the implications of these results for clinical treatment and patients' quality of life.
MeSH term(s)	Artificial Limbs/psychology ; Body Image ; Feedback, Sensory/physiology ; Human Body ; Humans ; Illusions/physiology ; Illusions/psychology ; Touch Perception/physiology
Language	English
Publishing date	2018-05-14
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	282464-4
ISSN	1873-7528 ; 0149-7634
ISSN (online)	1873-7528
ISSN	0149-7634
DOI	10.1016/j.neubiorev.2018.04.020
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Article ; Online: Functional neurological restoration of amputated peripheral nerve using biohybrid regenerative bioelectronics.

Rochford, Amy E / Carnicer-Lombarte, Alejandro / Kawan, Malak / Jin, Amy / Hilton, Sam / Curto, Vincenzo F / Rutz, Alexandra L / Moreau, Thomas / Kotter, Mark R N / Malliaras, George G / Barone, Damiano G

Science advances

2023 Volume 9, Issue 12, Page(s) eadd8162

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Rats ; Humans ; Animals ; Peripheral Nerves ; Electrodes ; Neurons ; Nerve Regeneration
Language	English
Publishing date	2023-03-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.add8162
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