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Neuropharmacology Feb 2021Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death in patients with refractory epilepsy. Centrally-mediated respiratory dysfunction has been...
Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death in patients with refractory epilepsy. Centrally-mediated respiratory dysfunction has been identified as one of the principal mechanisms responsible for SUDEP. Seizures generate a surge in adenosine release. Elevated adenosine levels suppress breathing. Insufficient metabolic clearance of a seizure-induced adenosine surge might be a precipitating factor in SUDEP. In order to deliver targeted therapies to prevent SUDEP, reliable biomarkers must be identified to enable prompt intervention. Because of the integral role of the phrenic nerve in breathing, we hypothesized that suppression of phrenic nerve activity could be utilized as predictive biomarker for imminent SUDEP. We used a rat model of kainic acid-induced seizures in combination with pharmacological suppression of metabolic adenosine clearance to trigger seizure-induced death in tracheostomized rats. Recordings of EEG, blood pressure, and phrenic nerve activity were made concomitant to the seizure. We found suppression of phrenic nerve burst frequency to 58.9% of baseline (p < 0.001, one-way ANOVA) which preceded seizure-induced death; importantly, irregularities of phrenic nerve activity were partly reversible by the adenosine receptor antagonist caffeine. Suppression of phrenic nerve activity may be a useful biomarker for imminent SUDEP. The ability to reliably detect the onset of SUDEP may be instrumental in the timely administration of potentially lifesaving interventions.
Topics: Adenosine Kinase; Animals; Kainic Acid; Male; Phrenic Nerve; Predictive Value of Tests; Rats; Rats, Wistar; Seizures; Sudden Unexpected Death in Epilepsy; Tubercidin
PubMed: 33212114
DOI: 10.1016/j.neuropharm.2020.108405 -
Biomedical Physics & Engineering Express Jan 2024Mechanical ventilation is essential in intensive care treatment but leads to diaphragmatic atrophy, which in turn contributes to prolonged weaning and increased...
Mechanical ventilation is essential in intensive care treatment but leads to diaphragmatic atrophy, which in turn contributes to prolonged weaning and increased mortality. One approach to prevent diaphragmatic atrophy while achieving pulmonary ventilation is electrical stimulation of the phrenic nerve. To automize phrenic nerve stimulation resulting in lung protective tidal volumes with lowest possible currents, mathematical models are required. Nerve stimulation models are often complex, so many parameters have to be identified prior to implementation. This paper presents a novel, simplified approach to model phrenic nerve excitation to obtain an individualized patient model using a few data points. The latter is based on the idea that nerve fibers are excited when the electric field exceeds a threshold. The effect of the geometry parameter on the model output was analyzed, and the model was validated with measurement data from a pig trial (RMSE in between 0.44 × 10and 1.64 × 10for parameterized models). The modeled phrenic nerve excitation behaved similarly to the measured tidal volumes, and thus could be used to develop automated phrenic nerve stimulation systems for lung protective ventilation.
Topics: Humans; Animals; Swine; Diaphragm; Phrenic Nerve; Respiration, Artificial; Electric Stimulation; Atrophy
PubMed: 38232399
DOI: 10.1088/2057-1976/ad1fa3 -
The American Journal of Forensic... Mar 2010The phrenic nerve arises in the neck. It is formed from C3, C4, and C5 nerve fibers and descends along the anterior surface of the scalenus anterior muscle before... (Review)
Review
"C3, 4, 5 Keeps the Diaphragm Alive." Is phrenic nerve palsy part of the pathophysiological mechanism in strangulation and hanging? Should diaphragm paralysis be excluded in survived cases?: A review of the literature.
The phrenic nerve arises in the neck. It is formed from C3, C4, and C5 nerve fibers and descends along the anterior surface of the scalenus anterior muscle before entering the thorax to supply motor and sensory input to the diaphragm. Its anatomic location in the neck leaves the nerve vulnerable to traumatic injury. Phrenic nerve injury can arise as a result of transection, stretching or compression of the nerve, and may result in paralysis of the diaphragm. Consequences of diaphragm paralysis include respiratory compromise, gastrointestinal obstruction, and cardiac arrhythmias. There may be serious morbidity and onset of symptoms may be delayed. Cases of diaphragm paralysis occurring as a consequence of neck trauma are documented in the literature. In some cases, the forces involved are relatively minor and include whiplash injury, occurring in minor motor vehicle collisions, chiropractic manipulation, and compression of neck structures, including a case involving external neck compression by industrial machinery. It is concluded that phrenic nerve palsy might be part of the pathophysiological mechanism in strangulation and hanging, and clinical investigation to exclude diaphragm paralysis in survived cases should be considered.
Topics: Asphyxia; Forensic Medicine; Humans; Neck Injuries; Phrenic Nerve; Respiratory Muscles; Respiratory Paralysis; Work of Breathing
PubMed: 19935388
DOI: 10.1097/PAF.0b013e3181c297e1 -
Thorax Nov 1987Phrenic nerve stimulation is often considered to be difficult and unreliable. The time taken for the phrenic nerves to be located and adequately stimulated was measured...
Phrenic nerve stimulation is often considered to be difficult and unreliable. The time taken for the phrenic nerves to be located and adequately stimulated was measured in 110 subjects, aged 21-89 years, 26 of whom had diaphragmatic weakness; and phrenic nerve conduction time was recorded in 76 of these individuals. Each phrenic nerve was stimulated transcutaneously in the neck with square wave impulses 0.1 ms in duration at 1 Hz and 80-160 volts while diaphragmatic muscle action potentials were recorded with surface electrodes. The time taken to locate either phrenic nerve ranged from two seconds to 22 minutes (median 10s). Both nerves were located in 83 of the 84 control subjects (99%) and in 21 of the 26 patients with diaphragmatic weakness (81%). Mean (SD) phrenic nerve conduction time in the control subjects was 6.94 (0.77) ms on the right and 6.61 (0.77) ms on the left. A weak relationship was found between conduction time and the subjects' age and height. Four out of 24 patients with diaphragmatic weakness had a prolonged phrenic nerve conduction time. Transcutaneous stimulation of the phrenic nerves was not a time consuming procedure, and it was well tolerated, reproducible, and successful in 95% of subjects.
Topics: Adult; Aged; Aged, 80 and over; Diaphragm; Electric Stimulation; Female; Humans; Male; Middle Aged; Muscular Diseases; Neural Conduction; Phrenic Nerve; Time Factors
PubMed: 3424270
DOI: 10.1136/thx.42.11.885 -
Journal of Cardiovascular... May 2014
Topics: Cardiac Resynchronization Therapy; Female; Heart Failure; Humans; Male; Phrenic Nerve; Ventricular Function, Left
PubMed: 24405146
DOI: 10.1111/jce.12365 -
Journal of Neurology, Neurosurgery, and... Oct 1967
Topics: Action Potentials; Adult; Aged; Diaphragm; Electric Stimulation; Electrophysiology; Humans; Intercostal Muscles; Middle Aged; Neural Conduction; Peripheral Nervous System Diseases; Phrenic Nerve; Reaction Time
PubMed: 4294147
DOI: 10.1136/jnnp.30.5.420 -
Chest May 2013
Topics: Electric Stimulation Therapy; Humans; Phrenic Nerve; Spinal Cord Injuries
PubMed: 23648903
DOI: 10.1378/chest.13-0219 -
Journal of Cardiovascular... Feb 2014Hemi-diaphragmatic paralysis is the most common complication associated with cryoballoon ablation for atrial fibrillation, yet the histopathology of phrenic nerve injury...
INTRODUCTION
Hemi-diaphragmatic paralysis is the most common complication associated with cryoballoon ablation for atrial fibrillation, yet the histopathology of phrenic nerve injury has not been well described.
METHODS AND RESULTS
A preclinical randomized study was conducted to characterize the histopathology of phrenic nerve injury induced by cryoballoon ablation and assess the potential for electromyographic (EMG) monitoring to limit phrenic nerve damage. Thirty-two dogs underwent cryoballoon ablation of the right superior pulmonary vein with the objective of inducing phrenic nerve injury. Animals were randomized 1:1 to standard monitoring (i.e., interruption of ablation upon reduction in diaphragmatic motion) versus EMG guidance (i.e., cessation of ablation upon a 30% reduction in the diaphragmatic compound motor action potential [CMAP] amplitude). The acute procedural endpoint was achieved in all dogs. Phrenic nerve injury was characterized by Wallerian degeneration, with subperineural injury to large myelinated axons and evidence of axonal regeneration. The degree of phrenic nerve injury paralleled the reduction in CMAP amplitude (P = 0.007). Animals randomized to EMG guidance had a lower incidence of acute hemi-diaphragmatic paralysis (50% vs 100%; P = 0.001), persistent paralysis at 30 days (21% vs 75%; multivariate odds ratio 0.12, 95% confidence interval [0.02, 0.69], P = 0.017), and a lesser severity of histologic injury (P = 0.001). Mature pulmonary vein ablation lesion characteristics, including circumferentiality and transmurality, were similar in both groups.
CONCLUSION
Phrenic nerve injury induced by cryoballoon ablation is axonal in nature and characterized by Wallerian degeneration, with potential for recovery. An EMG-guided approach is superior to standard monitoring in limiting phrenic nerve damage.
Topics: Animals; Cryosurgery; Dogs; Neuromuscular Monitoring; Peripheral Nerve Injuries; Phrenic Nerve; Treatment Outcome
PubMed: 24102792
DOI: 10.1111/jce.12296 -
Journal of Neurophysiology Dec 2017Large-diameter myelinated phrenic afferents discharge in phase with diaphragm contraction, and smaller diameter fibers discharge across the respiratory cycle. In this... (Review)
Review
Large-diameter myelinated phrenic afferents discharge in phase with diaphragm contraction, and smaller diameter fibers discharge across the respiratory cycle. In this article, we review the phrenic afferent literature and highlight areas in need of further study. We conclude that ) activation of both myelinated and nonmyelinated phrenic sensory afferents can influence respiratory motor output on a breath-by-breath basis; ) the relative impact of phrenic afferents substantially increases with diaphragm work and fatigue; ) activation of phrenic afferents has a powerful impact on sympathetic motor outflow, and ) phrenic afferents contribute to diaphragm somatosensation and the conscious perception of breathing. Much remains to be learned regarding the spinal and supraspinal distribution and synaptic contacts of myelinated and nonmyelinated phrenic afferents. Similarly, very little is known regarding the potential role of phrenic afferent neurons in triggering or modulating expression of respiratory neuroplasticity.
Topics: Animals; Diaphragm; Humans; Neuronal Plasticity; Neurons, Afferent; Nociception; Phrenic Nerve; Respiration
PubMed: 28835527
DOI: 10.1152/jn.00484.2017 -
Cirugia Espanola Feb 2019In surgical procedures of the supraclavicular and lateral cervical regions, as well as in cardiac and mediastinal surgeries, diaphragm function can be compromised by the...
In surgical procedures of the supraclavicular and lateral cervical regions, as well as in cardiac and mediastinal surgeries, diaphragm function can be compromised by the risk of injury to the phrenic nerve and/or the C4 root. There are few publications that treat the intraoperative stimulation of these nerve structures to evaluate their functionality and, to our knowledge, until now it has not been hypothesized about whether it is possible to reduce the injury rates, which reach 26% in some cardiac surgery studies. We describe the technique used for the neurophysiological monitoring of the phrenic nerve. Also, its usefulness and advantages over other techniques are discussed. We conclude that, with the increasing incorporation in recent years of intraoperative neurophysiological monitoring, its application to the phrenic nerve is possible in procedures with a risk of injury and, thus, the reduction of iatrogenic injury rates may be feasible.
Topics: Humans; Intraoperative Neurophysiological Monitoring; Phrenic Nerve
PubMed: 30580833
DOI: 10.1016/j.ciresp.2018.11.002