Nat Rev Neurol. 2024 Apr 3. doi: 10.1038/s41582-024-00953-z. Online ahead of print.

ABSTRACT

Neurostimulation, the use of electrical stimulation to modulate the activity of the nervous system, is now commonly used for the treatment of chronic pain, movement disorders and epilepsy. Many neurostimulation techniques have now shown promise for the treatment of physical impairments in people with stroke. In 2021, vagus nerve stimulation was approved by the FDA as an adjunct to intensive rehabilitation therapy for the treatment of chronic upper extremity deficits after ischaemic stroke. In 2024, pharyngeal electrical stimulation was conditionally approved by the UK National Institute for Health and Care Excellence for neurogenic dysphagia in people with stroke who have a tracheostomy. Many other approaches have also been tested in pivotal device trials and a number of approaches are in early-phase study. Typically, neurostimulation techniques aim to increase neuroplasticity in response to training and rehabilitation, although the putative mechanisms of action differ and are not fully understood. Neurostimulation techniques offer a number of practical advantages for use after stroke, such as precise dosing and timing, but can be invasive and costly to implement. This Review focuses on neurostimulation techniques that are now in clinical use or that have reached the stage of pivotal trials and show considerable promise for the treatment of post-stroke impairments.

PMID:38570705 | DOI:10.1038/s41582-024-00953-z

Bioelectron Med. 2024 Apr 3;10(1):9. doi: 10.1186/s42234-024-00142-9.

ABSTRACT

The vagus nerve has an anti-inflammatory effect through the inflammatory reflex, which inhibits the release of proinflammatory cytokines by macrophages. Recent pilot clinical trials, using implantable bioelectronic devices, have demonstrated the efficacy of vagus nerve stimulation in adult patients with rheumatoid arthritis and inflammatory bowel diseases as an alternative to drugs, which are not devoid of side effects and are costly. In this issue of Bioelectronic Medicine, Peterson et al. report the safety of novel implantable neuroimmune modulation device for treating rheumatoid arthritis (The RESET RA study), which I will discuss in this commentary.

PMID:38566215 | PMC:PMC10988796 | DOI:10.1186/s42234-024-00142-9

Biomed Phys Eng Express. 2024 Apr 2. doi: 10.1088/2057-1976/ad3968. Online ahead of print.

ABSTRACT

To treat diseases associated with vagal nerve control of peripheral organs, it is necessary to selectively activate efferent and afferent fibers in the vagus. As a result of the nerve’s complex anatomy, fiber-specific activation proves challenging. Spatially selective neuromodulation using micromagnetic stimulation(µMS) is showing incredible promise. This neuromodulation technique uses microcoils(µcoils) to generate magnetic fields by powering them with a time-varying current. Following the principles of Faraday’s Law of Electromagnetic Induction, a highly directional electric field is induced in the nerve from the magnetic field. In this study on rodent cervical vagus, a solenoidal-shaped μcoil was oriented at an angle to left and right branches of the nerve. The aim of this study was to measure changes in the mean arterial pressure (MAP) and heart rate (HR) following μMS of the vagus. The µcoils were powered by a single-cycle sinusoidal current varying in pulse widths(PW = 100, 500, and 1000 µsec) at a frequency of 20 Hz. Under the influence of isoflurane, µMS of the left vagus at 1000 µsec PW led to an average drop in MAP of 16.75 mmHg(n = 7). In contrast, µMS of the right vagus under isoflurane resulted in an average drop of 11.93 mmHg in the MAP(n = 7). Surprisingly, there were no changes in HR to either right or left vagal µMS suggesting the drop in MAP associated with vagus µMS was the result of stimulation of afferent, but not efferent fibers. In urethane anesthetized rats, no changes in either MAP or HR were observed upon μMS of the right or left vagus(n = 3). These findings suggest the choice of anesthesia plays a key role in determining the efficacy of μMS on the vagal nerve. Absence of HR modulation upon μMS could offer alternative treatment options using VNS with fewer heart-related side-effects.

PMID:38565093 | DOI:10.1088/2057-1976/ad3968

medRxiv [Preprint]. 2024 Mar 19:2024.03.18.24304239. doi: 10.1101/2024.03.18.24304239.

ABSTRACT

BACKGROUND: Inflammation has been implicated in driving the morbidity associated with subarachnoid hemorrhage (SAH). Despite understanding the important role of inflammation in morbidity following SAH, there is no current effective way to modulate this deleterious response. There is a critical need for a novel approach to immunomodulation that can be safely, rapidly, and effectively deployed in SAH patients. Vagus nerve stimulation (VNS) provides a non-pharmacologic approach to immunomodulation, with prior studies demonstrating VNS can reduce systemic inflammatory markers, and VNS has had early success treating inflammatory conditions such as arthritis, sepsis, and inflammatory bowel diseases. The aim of the Non-invasive Auricular Vagus nerve stimulation for Subarachnoid Hemorrhage (NAVSaH) trial is to translate the use of non-invasive transcutaneous auricular VNS (taVNS) to spontaneous SAH, with our central hypothesis being that implementing taVNS in the acute period following spontaneous SAH attenuates the expected inflammatory response to hemorrhage and curtails morbidity associated with inflammatory-mediated clinical endpoints.

MATERIALS AND METHODS: The overall objectives for the NAHSaH trial are to 1) Define the impact that taVNS has on SAH-induced inflammatory markers in the plasma and cerebrospinal fluid (CSF), 2) Determine whether taVNS following SAH reduces radiographic vasospasm, and 3) Determine whether taVNS following SAH reduces chronic hydrocephalus. Following presentation to a single enrollment site, enrolled SAH patients are randomly assigned twice daily treatment with either taVNS or sham stimulation for the duration of their intensive care unit stay. Blood and CSF are drawn before initiation of treatment sessions, and then every three days during a patient’s hospital stay. Primary endpoints include change in the inflammatory cytokine TNF-α in plasma and cerebrospinal fluid between day 1 and day 13, rate of radiographic vasospasm, and rate of requirement for long-term CSF diversion via a ventricular shunt. Secondary outcomes include exploratory analyses of a panel of additional cytokines, number and type of hospitalized acquired infections, duration of external ventricular drain in days, interventions required for vasospasm, continuous physiology data before, during, and after treatment sessions, hospital length of stay, intensive care unit length of stay, and modified Rankin Scale score (mRS) at admission, discharge, and each at follow-up appointment for up to two years following SAH.

DISCUSSION: Inflammation plays a central role in morbidity following SAH. This NAVSaH trial is innovative because it diverges from the pharmacologic status quo by harnessing a novel non-invasive neuromodulatory approach and its known anti-inflammatory effects to alter the pathophysiology of SAH. The investigation of a new, effective, and rapidly deployable intervention in SAH offers a new route to improve outcomes following SAH.

TRIAL REGISTRATION: Clinical Trials Registered, NCT04557618 . Registered on September 21, 2020, and the first patient was enrolled on January 4, 2021.

PMID:38562875 | PMC:PMC10984059 | DOI:10.1101/2024.03.18.24304239

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2024 Mar 7;59(3):233-237. doi: 10.3760/cma.j.cn115330-20231120-00228.

ABSTRACT

Objective: To investigate the application value of intraoperative motor nerve monitoring in cervical neurogenic tumor surgery. Methods: The efficacy of intraoperative neuromonitoring (IONM) was analyzed retrospectively in 18 patients, including 6 males and 12 females, aged from 15 to 74 years, treated in Affiliated Drum Tower Hospital, Medical School of Nanjing University from June 2019 to September 2022 who underwent total cystectomy of cervical neurogenic tumors under intraoperative nerve monitoring. Results: All 18 patients had complete tumor removal, including 8 patients with tumors from the vagus nerve and 10 patients with tumors from the brachial plexus nerve. Postoperative nerve functions were normal in patients with tumors from brachial plexus nerve, and incomplete vocal cord paralysis occurred in 2 patients with tumors from vagus vagus nerve. The total incidence of motor nerve injury was 11.1% (2/18). All patients were followed up for 6 to 45 months, with no tumor recurrence. Conclusion: Intraoperative neuromonitoring has significant values in surgery of cervical neurogenic tumors, which is helpful to remove completely the tumors on the basis of protecting the nerve functions to the maximum extent.

PMID:38561261 | DOI:10.3760/cma.j.cn115330-20231120-00228

Vet Radiol Ultrasound. 2024 Mar 28. doi: 10.1111/vru.13359. Online ahead of print.

ABSTRACT

A chronic cough, gag, or retch is a common presenting clinical complaint in dogs. Those refractory to conservative management frequently undergo further diagnostic tests to investigate the cause, including CT examination of their head, neck, and thorax for detailed morphological assessment of their respiratory and upper gastrointestinal tract. This case series describes five patients with CT characteristics consistent with an intracranial and jugular foraminal mass of the combined glossopharyngeal (IX), vagus (X), and accessory (XI) cranial nerves and secondary features consistent with their paresis. The consistent primary CT characteristics included an intracranial, extra-axial, cerebellomedullary angle, and jugular foraminal soft tissue attenuating, strongly enhancing mass (5/5). Secondary characteristics included smooth widening of the bony jugular foramen (5/5), mild hyperostosis of the petrous temporal bone (3/5), isolated severe atrophy of the ipsilateral sternocephalic, cleidocephalic, and trapezius muscles (5/5), atrophy of the ipsilateral thyroarytenoideus and cricoarytenoideus muscles of the vocal fold (5/5), and an ipsilateral “dropped” shoulder (4/5). Positional variation of the patient in CT under general anesthesia made the “dropped” shoulder of equivocal significance. The reported clinical signs and secondary CT features reflect a unilateral paresis of the combined cranial nerves (IX, X, and XI) and are consistent with jugular foramen syndrome/Vernet’s syndrome reported in humans. The authors believe this condition is likely chronically underdiagnosed without CT examination, and this case series should enable earlier CT diagnosis in future cases.

PMID:38549218 | DOI:10.1111/vru.13359

Int J Mol Sci. 2024 Mar 18;25(6):3411. doi: 10.3390/ijms25063411.

ABSTRACT

Vitiligo is a complex skin disorder that involves oxidative stress and inflammatory responses and currently lacks a definitive cure. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive method for targeting the auricular branch of the vagus nerve and has gained widespread attention for potential intervention in the autonomic nervous system. Although previous research has suggested that vagus nerve stimulation can potentially inhibit inflammatory responses, its specific role and mechanisms in vitiligo treatment remain unknown. This study aimed to explore the therapeutic effects of taVNS in a mouse model of vitiligo induced by monobenzone. Initially, a quantitative assessment of the treatment effects on vitiligo mice was conducted using a scoring system, revealing that taVNS significantly alleviated symptoms, particularly by reducing the depigmented areas. Subsequent immunohistochemical analysis revealed the impact of taVNS treatment on melanocyte granules, mitigating pigment loss in the skin of monobenzone-induced vitiligo mice. Further analysis indicated that taVNS exerted its therapeutic effects through multiple mechanisms, including the regulation of oxidative stress, enhancement of antioxidant capacity, promotion of tyrosine synthesis, and suppression of inflammatory responses. The conclusions of this study not only emphasize the potential value of taVNS in vitiligo therapy, but also lay a foundation for future research into the mechanisms and clinical applications of taVNS.

PMID:38542385 | PMC:PMC10970032 | DOI:10.3390/ijms25063411

Biomedicines. 2024 Mar 1;12(3):557. doi: 10.3390/biomedicines12030557.

ABSTRACT

This study investigates the dose-dependent EEG effects of Vagus Nerve Stimulation (VNS) in patients with drug-resistant epilepsy. This research examines how varying VNS intensities impacts EEG power spectrum and synchronization in a cohort of 28 patients. Patients were categorized into responders, partial-responders, and non-responders based on seizure frequency reduction. The methods involved EEG recordings at incremental VNS intensities, followed by spectral and synchronization analysis. The results reveal significant changes in EEG power, particularly in the delta and beta bands across different intensities. Notably, responders exhibited distinct EEG changes compared to non-responders. Our study has found that VNS intensity significantly influences EEG power topographic allocation and brain desynchronization, suggesting the potential use of acute dose-dependent effects to personalized VNS therapy in the treatment of epilepsy. The findings underscore the importance of individualized VNS dosing for optimizing therapeutic outcomes and highlight the use of EEG metrics as an effective tool for monitoring and adjusting VNS parameters. These insights offer a new avenue for developing individualized VNS therapy strategies, enhancing treatment efficacy in epilepsy.

PMID:38540170 | PMC:PMC10968041 | DOI:10.3390/biomedicines12030557

Cureus. 2024 Feb 25;16(2):e54863. doi: 10.7759/cureus.54863. eCollection 2024 Feb.

ABSTRACT

Epilepsy, a widespread neurological disorder characterized by recurrent seizures, affects millions globally, with a significant impact on the pediatric population. Antiepileptic drugs (AEDs) constitute the primary treatment; however, drug-resistant epilepsy (DRE), especially in children, poses a therapeutic challenge. Alternative interventions, such as surgery, vagus nerve stimulation, and the ketogenic diet (KD), have been explored. This systematic review aims to investigate various types of KDs, their distinctions, their effectiveness, and their safety concerning the reduction of seizure frequency, achieving seizure freedom, and the occurrence of adverse events. The study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive search was conducted using databases such as PubMed Central (PMC), MedLine, and Science Direct to identify relevant articles. Eligibility criteria and quality assessment tools were applied to evaluate the potential risk of bias and select 11 articles for inclusion in this review. The selected articles encompassed four randomized controlled trials (RCTs), two systematic reviews, and five narrative reviews. The data collected for this review was completed on October 2, 2023. Challenges, such as palatability, cultural factors, and adherence difficulties, were identified. Family or caregiver involvement plays a pivotal role in treatment success. Despite numerous RCTs and reviews, information gaps persist, hindering conclusive outcomes. Evaluating the risk-benefit ratio is crucial, considering potential side effects. The highly individualized nature of KD therapy, influenced by diverse seizure types and syndromes, necessitates a trial-and-error approach monitored by a multidisciplinary team. Long-term safety and efficacy demand continuous real-life patient data review. In summary, while KD presents a promising alternative for DRE, its success relies on meticulous planning, individualized implementation, and ongoing research to address existing challenges and information gaps.

PMID:38533170 | PMC:PMC10964213 | DOI:10.7759/cureus.54863

Ann Clin Transl Neurol. 2024 Mar 26. doi: 10.1002/acn3.52029. Online ahead of print.

ABSTRACT

OBJECTIVE: In parallel to standard vagus nerve stimulation (VNS), microburst stimulation delivery has been developed. We evaluated the fMRI-related signal changes associated with standard and optimized microburst stimulation in a proof-of-concept study (NCT03446664).

METHODS: Twenty-nine drug-resistant epilepsy patients were prospectively implanted with VNS. Three 3T fMRI scans were collected 2 weeks postimplantation. The maximum tolerated VNS intensity was determined prior to each scan starting at 0.125 mA with 0.125 mA increments. FMRI scans were block-design with alternating 30 sec stimulation [ON] and 30 sec no stimulation [OFF]: Scan 1 utilized standard VNS and Scan 3 optimized microburst parameters to determine target settings. Semi-automated on-site fMRI data processing utilized ON-OFF block modeling to determine VNS-related fMRI activation per stimulation setting. Anatomical thalamic mask was used to derive highest mean thalamic t-value for determination of microburst stimulation parameters. Paired t-tests corrected at P < 0.05 examined differences in fMRI responses to each stimulation type.

RESULTS: Standard and microburst stimulation intensities at Scans 1 and 3 were similar (P = 0.16). Thalamic fMRI responses were obtained in 28 participants (19 with focal; 9 with generalized seizures). Group activation maps showed standard VNS elicited thalamic activation while optimized microburst VNS showed widespread activation patterns including thalamus. Comparison of stimulation types revealed significantly greater cerebellar, midbrain, and parietal fMRI signal changes in microburst compared to standard VNS. These differences were not associated with seizure responses.

INTERPRETATION: While standard and optimized microburst VNS elicited thalamic activation, microburst also engaged other brain regions. Relationship between these fMRI activation patterns and clinical response warrants further investigation.

CLINICAL TRIAL REGISTRATION: The study was registered with clinicaltrials.gov (NCT03446664).

PMID:38532258 | DOI:10.1002/acn3.52029