Article
Neurosciences
Yazi Al'joboori, Ricci Hannah, Francesca Lenham, Pia Borgas, Charlotte J. P. Kremers, Karen L. Bunday, John Rothwell, Lynsey D. Duffell
Summary: Rehabilitative interventions involving electrical stimulation, such as transcutaneous Spinal Cord stimulation (tSCS) and Peripheral Nerve Stimulation (PNS), show promise for neuroplastic recovery in people living with Spinal Cord Injury (SCI). This study compared the immediate and short-term effects of pairing Transcranial Magnetic Stimulation (TMS) with tSCS or PNS on Corticospinal excitability in healthy subjects, demonstrating that tSCS can increase corticospinal excitability, potentially optimizing stimulation parameters for neuroplasticity in individuals with SCI.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Jeonghoon Oh, Alexander G. Steele, Blesson Varghese, Catherine A. Martin, Michelle S. Scheffler, Rachel L. Markley, Yi-Kai Lo, Dimitry G. Sayenko
Summary: Transcutaneous spinal stimulation is a promising method for restoring upper limb function in patients with spinal cord injuries. By selectively stimulating different electrode placements, specific groups of upper limb muscles can be activated. This approach may enhance efficacy and help patients recover more diverse motor activities.
Review
Biochemistry & Molecular Biology
Ben Kaplan, Shulamit Levenberg
Summary: Peripheral nerve and spinal cord injuries have significant impacts on patients' lives, with severe cases currently lacking a cure. Biomaterials can be engineered as scaffolds to mimic nerve tissue and promote axonal regeneration, as well as deliver therapeutic agents to the site of injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Jaclyn R. Wecht, William M. Savage, Grace O. Famodimu, Gregory A. Mendez, Jonah M. Levine, Matthew T. Maher, Joseph P. Weir, Jill M. Wecht, Jason B. Carmel, Yu-Kuang Wu, Noam Y. Harel
Summary: The study found that subthreshold TSCS can facilitate hand muscle responses to motor cortex stimulation, especially when the TSCS arrives simultaneously or slightly after the cortical stimulation, indicating the potential for enhanced synaptic plasticity in circuits serving hand function.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Medicine, General & Internal
Md Akhlasur Rahman, Niraj Singh Tharu, Sylvia M. Gustin, Yong-Ping Zheng, Monzurul Alam
Summary: Spinal cord injury (SCI) is a debilitating injury with severe complications, but recent development of noninvasive electrical neuromodulation treatments offers hope for rehabilitation. Trans-spinal direct current stimulation (tsDCS) and trans-spinal pulsed current stimulation (tsPCS) have shown promising results in improving sensorimotor and autonomic functions.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Hatice Kumru, Loreto Garcia-Alen, Aina Ros-Alsina, Sergiu Albu, Margarita Valles, Joan Vidal
Summary: This study aimed to investigate whether transcutaneous spinal cord stimulation (tSCS) could improve respiratory function in individuals with cervical spinal cord injury (cSCI). The results showed that subjects who received tSCS combined with inspiratory muscle training (IMT) experienced significant improvements in breathlessness/dyspnea, hypophonia, maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and forced vital capacity. Therefore, tSCS may serve as an effective adjunctive therapy for respiratory impairments following SCI.
Review
Engineering, Biomedical
Emi A. Kiyotake, Michael D. Martin, Michael S. Detamore
Summary: This review discusses the potential of regenerative medicine and rehabilitation approaches for SCI, as well as the role of conductive biomaterials in synergizing these two fields. Current limitations and translational challenges for conductive biomaterials in becoming therapeutics for SCI are identified.
ACTA BIOMATERIALIA
(2022)
Article
Neurosciences
Wenbin Guo, Katherine Shapiro, Zhaoxia Wang, Kody Armann, Bing Shen, Jicheng Wang, James R. Roppolo, William C. de Groat, Changfeng Tai
Summary: This study successfully induced efficient and low-pressure voiding in chronic SCI cats by implanting a PNS, suggesting the potential development of a novel neuroprosthesis for humans to restore bladder function after SCI.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Neurosciences
Santosh Chandrasekaran, Nikunj A. Bhagat, Richard Ramdeo, Sadegh Ebrahimi, Pawan D. Sharma, Doug G. Griffin, Adam Stein, Susan J. Harkema, Chad E. Bouton
Summary: Peripheral nerve injury can cause chronic pain, paralysis, and loss of sensation, which seriously affects one's quality of life. While spinal cord stimulation has been used for pain relief, its potential for restoring function after peripheral nerve injury has not been explored. This study demonstrates the effectiveness of targeted transcutaneous spinal cord stimulation in restoring strength and improving hand dexterity in an individual with paralysis due to peripheral nerve injury. The gains in motor and sensory functions persisted months after stimulation, suggesting the long-lasting benefits of this non-invasive therapeutic approach.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Rehabilitation
Amira Hassan Bekhet, Alhadi M. Jahan, Vanesa Bochkezanian, Kristin E. Musselman, Amr A. Elsareih, Ashraf S. Gorgey
Summary: The objective of this study was to determine the effects of neuromuscular electrical stimulation (NMES) or functional electrical stimulation (FES), or both, training on different body composition parameters in individuals with spinal cord injury. The findings suggest that NMES/FES is an effective rehabilitation strategy for muscle hypertrophy and increasing lean mass (LM). Weekly training volumes are associated with muscle hypertrophy after NMES loading exercise. However, there is a lack of rationale for the selection of stimulation parameters.
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
(2022)
Article
Neurosciences
Jesse K. Niehaus, Bonnie Taylor-Blake, Lipin Loo, Jeremy M. Simon, Mark J. Zylka
Summary: Peripheral nerve injury leads to long-term pro-inflammatory responses in spinal cord glial cells, but the identity of endogenous cells that resolve spinal inflammation has not been determined. Our study demonstrates that MRC1(+) spinal cord macrophages actively restrain glia to limit neuroinflammation and resolve mechanical pain following superficial injury, suggesting that therapeutic modulation of spinal macrophages could promote long-lasting recovery of neuropathic pain.
Article
Neurosciences
Hui Chen, Zhou Feng, Lingxia Min, Mingliang Tan, Dongyun Zhang, Qiuwen Gong, Hongliang Liu, Jingming Hou
Summary: This study demonstrated that activated microglia produce TNF-a to induce endothelial necroptosis via the RIP1/RIP3/MLKL pathway, leading to BSCB disruption after SCI. The use of TNF-a-specific antibody and necroptosis inhibitor alleviates BSCB disruption. VNS inhibits microglia-derived TNF-a production and reduces the expression of p-RIP3 and p-MLKL, thus mitigating BSCB disruption and reducing neuroinflammation and neural damage.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Engineering, Biomedical
Sarah Massey, Danielle Konig, Pratham Upadhyay, Zehra Beril Evcil, Rebbekha Melin, Memoona Fatima, Ricci Hannah, Lynsey Duffell
Summary: This study compared the effects of sub-threshold TSCS and TSCS-kHz at similar relative intensities to their own threshold. The results showed that TSCS-kHz decreased spinal excitability while TSCS did not. Additionally, TSCS-kHz had a greater effect on motor-evoked potential amplitude compared to TSCS at higher intensities.
Article
Neurosciences
Jacob Kjell, Mikael Svensson
Summary: Peripheral nerves have the ability to promote axon growth and regeneration, making them a potential repair strategy for spinal cord injuries. However, there is still limited understanding of the formation of new circuitries and functional outcomes associated with the use of peripheral nerve grafts.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Chaoling Xu, Fan Zeng, Danyu Wu, Pang Wang, Xiaoling Yin, Bin Jia
Summary: Spinal cord injury (SCI) is a difficult-to-treat and common neurological disorder causing long-lasting and severe pain. Electrical stimulation on the dorsal side of the spinal cord has been proven to be a valuable therapeutic tool, but its development is hindered by costly equipment and complex design. Recent advancements in wearable and implantable triboelectric nanogenerators (TENGs) using nanofiber membranes on clothing have provided a new opportunity for the development of nerve stimulation.
FRONTIERS IN CHEMISTRY
(2022)
Review
Clinical Neurology
Mansur A. Kutlubaev, Jashelle Caga, Ying Xu, Daria K. Areprintseva, Ekaterina Pervushina, Matthew C. Kiernan
Summary: This study aimed to determine the frequency and correlates of apathy in ALS and its impact on the disease prognosis. The findings suggest that the emergence of apathy is associated with cognitive decline and bulbar onset of the disease. Additionally, ALS patients with apathy showed more prominent changes in structural and functional brain imaging. Apathy worsened the long-term prognosis of ALS.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Clinical Neurology
Andrew Hannaford, Karen Byth, Nathan Pavey, Robert D. Henderson, Susan Mathers, Merrilee Needham, David Schultz, Parvathi Menon, Matthew C. Kiernan, Steve Vucic
Summary: This study aimed to assess the utility of clinical biomarkers, such as Delta FS and BMI, and neurophysiological measures, such as SI and NPI, in monitoring disease progression in ALS patients. The results showed that Delta FS and BMI were predictive of disease severity and progression, while SI and NPI were associated with disease severity. The implementation of these biomarkers could assist in patient management and stratification into clinical trials.
Article
Clinical Neurology
Matthew Silsby, Alessandro F. Fois, Con Yiannikas, Karl Ng, Matthew C. Kiernan, Victor S. C. Fung, Steve Vucic
Summary: This study aimed to evaluate tremor in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and test the hypothesis that tremor occurs due to mistimed peripheral inputs affecting central motor processing, as established in other demyelinating neuropathies. Additionally, the tremor stability index (TSI) was calculated to assess the variability of CIDP-related tremor compared to other tremor disorders.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Neurosciences
Eduardo Martinez-Valdes, Roger M. Enoka, Ales Holobar, Kevin McGill, Dario Farina, Manuela Besomi, Francois Hug, Deborah Falla, Richard G. Carson, Edward A. Clancy, Catherine Disselhorst-Klug, Jaap H. van Dieen, Kylie Tucker, Simon Gandevia, Madeleine Lowery, Karen Sogaard, Thor Besier, Roberto Merletti, Matthew C. Kiernan, John C. Rothwell, Eric Perreault, Paul W. Hodges
Summary: The analysis of single motor unit (SMU) activity is crucial for understanding the neural strategies controlling muscle force. Traditionally, this analysis has been done invasively through intramuscular electromyography (EMG), but recent advances in signal processing techniques have enabled the identification of SMU activity in high-density surface electromyography (HDsEMG) recordings.
JOURNAL OF ELECTROMYOGRAPHY AND KINESIOLOGY
(2023)
Review
Clinical Neurology
Sean W. Willemse, Peter Harley, Ruben P. A. van Eijk, Koen C. Demaegd, Pavol Zelina, R. Jeroen Pasterkamp, Philip van Damme, Caroline Ingre, Wouter van Rheenen, Jan H. Veldink, Matthew C. Kiernan, Ammar Al-Chalabi, Leonard H. van den Berg, Pietro Fratta, Michael A. van Es
Summary: Amyotrophic lateral sclerosis (ALS) is a deadly neurodegenerative disease with limited treatment options. A specific gene polymorphism in the UNC13A gene has been found to increase the risk of ALS and frontotemporal dementia (FTD), and can modify the disease phenotype in ALS patients. UNC13A is involved in maintaining synaptic active zones and its depletion leads to impaired neurotransmission. Recent discoveries have identified UNC13A as a potential therapeutic target, with ongoing trials using lithium carbonate and considering antisense oligonucleotides. Knowledge of UNC13A's distinct phenotype is important for future clinical trials.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Neuroimaging
Nga Yan Tse, Martina Bocchetta, Emily G. Todd, Emma M. Devenney, Sicong Tu, Jashelle Caga, John R. Hodges, Glenda M. Halliday, Muireann Irish, Matthew C. Kiernan, Olivier Piguet, Jonathan D. Rohrer, Rebekah M. Ahmed
Summary: Through studying a large sample of 211 participants, it was found that different subregions of the hypothalamus are correlated with cognitive and behavioral impairments. Patients with ALS, mixed ALS-FTD, and bvFTD all showed hypothalamic involvement. Cognitive and behavioral symptoms were correlated with bilateral involvement of the anterior inferior, anterior superior, and posterior hypothalamic subregions. The anterior superior and superior tuberal subregions displayed the greatest volume loss in bvFTD and ALS-FTD, and ALS, respectively, and were associated with specific neuropeptide expression abnormalities.
NEUROIMAGE-CLINICAL
(2023)
Letter
Clinical Neurology
Michelle A. Farrar, Matthew C. Kiernan, Didu S. Kariyawasam
Article
Clinical Neurology
Parvathi Menon, Nathan Pavey, Aman S. Aberra, Mehdi A. J. van den Bos, Ruochen Wang, Matthew C. Kiernan, Angel Peterchev, Steve Vucic
Summary: The aim of this study was to investigate the effects of different combinations of TMS pulse width and pulse shape on cortical strength-duration time constant (SDTC) and rheobase measurements. The results showed that the M-ratio had a significant effect on SDTC, with longer durations for higher M-ratios. Rheobase was smaller for higher M-ratios. The most consistent values of SDTC and rheobase were obtained with specific sets of pulse widths. Simulation studies indicated that changes in transient Na' channel conductance could account for the changes in SDTC.
CLINICAL NEUROPHYSIOLOGY
(2023)
Review
Clinical Neurology
Steve Vucic, Kai-Hsiang Stanley Chen, Matthew C. Kiernan, Mark Hallett, David. H. Benninger, Vincenzo Di Lazzaro, Paolo M. Rossini, Alberto Benussi, Alfredo Berardelli, Antonio Curra, Sandro M. Krieg, Jean-Pascal Lefaucheur, Yew Long Lo, Richard A. Macdonell, Marcello Massimini, Mario Rosanova, Thomas Picht, Cathy M. Stinear, Walter Paulus, Yoshikazu Ugawa, Ulf Ziemann, Robert Chen
Summary: This review provides a comprehensive update on the clinical diagnostic utility of transcranial magnetic stimulation (TMS) in neurological diseases. TMS techniques have demonstrated clinical utility in various neurodegenerative, movement, episodic, chronic pain, and functional diseases. TMS measures can aid in the diagnosis of amyotrophic lateral sclerosis, stroke, myelopathy, and Alzheimer's disease, among others. Combining TMS with electroencephalography allows for the measurement of parameters altered in neurological disorders.
CLINICAL NEUROPHYSIOLOGY
(2023)
Article
Neurosciences
Yoshimitsu Shimatani, Cindy Shin-Yi Lin, Jose Manuel Matamala, Matthew C. Kiernan
Summary: This series of studies aimed to investigate the biophysical basis underlying differences in behavior between motor and sensory axons at different target response levels. The study found that strength-duration time constants were longer at lower target levels for both motor and sensory axons. Additionally, the threshold change at 0.2 ms was higher in sensory axons. Significant relationships were found between the threshold change at 0.2 ms and strength-duration time constants across all target levels. Mathematical modeling revealed that the observed differences were not solely due to a persistent Na thorn current, but other factors such as internodal leak conductance and hyperpolarization-activated cation current also played a role.
JOURNAL OF NEUROPHYSIOLOGY
(2023)
Article
Multidisciplinary Sciences
Lyndal Henden, Liam G. Fearnley, Natalie Grima, Emily P. McCann, Carol Dobson-Stone, Lauren Fitzpatrick, Kathryn Friend, Lynne Hobson, Sandrine Chan Moi Fat, Dominic B. Rowe, Susan D'Silva, John B. Kwok, Glenda M. Halliday, Matthew C. Kiernan, Srestha Mazumder, Hannah C. Timmins, Margaret Zoing, Roger Pamphlett, Lorel Adams, Melanie Bahlo, Ian P. Blair, Kelly L. Williams
Summary: In this study, we analyzed whole-genome sequencing data from 608 patients with sporadic ALS, 68 patients with sporadic FTD, and 4703 matched controls using three tools. We found that 17.6% of clinically diagnosed ALS and FTD cases had expanded STR alleles reported to be pathogenic or intermediate for other neurodegenerative diseases, providing evidence for their contribution to the development of these diseases. We also identified multiple disease-relevant STR expansions associated with neurodegenerative diseases, highlighting the clinical and pathological pleiotropy of neurodegenerative disease genes and their importance in ALS and FTD.
Article
Clinical Neurology
Nathan Pavey, Andrew Hannaford, Mana Higashihara, Mehdi van den Bos, Matthew C. Kiernan, Parvathi Menon, Steve Vucic
Summary: The split hand index (SI) derived by different methods showed potential as a diagnostic biomarker in ALS, with SICMAP amp and SIMScanFit-MUNE demonstrating greater utility in distinguishing ALS from mimic disorders.
CLINICAL NEUROPHYSIOLOGY
(2023)
Article
Clinical Neurology
Monica Pinkerton, Guinevere Lourenco, Maria Torres Pacheco, Glenda M. Halliday, Matthew C. Kiernan, Rachel H. Tan
Summary: This study aimed to assess the pathology of p62 in sporadic ALS patients and determine its association with disease pathology. The results identified more cytoplasmic p62 aggregates in patients with a shorter disease duration. The findings support further research on p62 as a potential prognostic biomarker in ALS.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Letter
Clinical Neurology
Gianni Sesa-Ashton, Vaughan G. Macefield
CLINICAL AUTONOMIC RESEARCH
(2023)