Analysis of reflex activity in cardiac sympathetic nerve induced by myelinated phrenic nerve afferents

Electrical stimulation of the phrenic nerve afferents evoked excitatory responses in the right inferior cardiac sympathetic nerve in chloralose-anaesthetized cats. The reflex was recorded in intact and spinal cats. The latency and threshold of the volley recorded from the phrenic nerve as well as of the cord dorsum potentials evoked by electrical stimulation of the phrenic nerve indicated that group III afferents were responsible for this reflex. The phrenicocardiac sympathetic reflex recorded in intact cats was followed by a silent period. The maximum amplitude of the reflex discharges was 800 microV, the latency was 83 ms and the central transmission time 53 ms. Duration of the silent period lasted up to 0.83 s. In spinal cats the reflex was recorded 5.5-8 h after spinalization. The maximum amplitude of the spinal reflex discharges ranged from 22 to 91 microV and the latency from 36 to 66 ms.     

A comprehensive electrophysiological evaluation of phrenic nerve injury related to open-heart surgery

A prospective electrophysiological study of phrenic nerve was performed in 59 subjects undergoing open-heart surgery. The nerve was stimulated percutaneously at the neck and the diaphragmatic response was recorded with surface electrodes placed over the 8th intercostal space. The latency, amplitude, duration and area of the evoked response were measured before and after the operation. Post-operatively no response was elicited in 2 patients bilaterally, in 5 from the left and in 2 from the right. Comparison of the post-operative with the pre-operative group values in the remaining subjects showed that the amplitude and area of the left phrenic were lower in the post-operative study, indicating that some of the nerve fibres were not conducting. There were no statistically significant differences between pre and post-operative values of latency or duration on the left or any of the parameters on the right. Our findings suggest that the amplitude and area of the diaphragmatic response are more sensitive than latency in detecting phrenic nerve paresis associated with open-heart surgery.     

Supraspinal regulation of spinal reflex discharge into cardiac sympathetic nerves

(1) In chloralose anaesthetized cats, reflex responses were recorded in inferior cardiac nerves following stimulation of intercostal nerves and hind limb afferent nerves. (2) In 80% of cats, a long latency reflex response alone was recorded, whereas, in the others, a short and long latency response was present to intercostal nerve stimulation. (3) In cats displaying only a long latency somatocardiac reflex response, damage to the ventral quadrant of the ipsilateral cervical spinal cord, through which runs a bulbospinal inhibitory pathway, resulted in the appearance of shorter latency reflexes to intercostal nerve stimulation. Lesions elsewhere in the cervical cord did not do this. (4) The characteristics of the early responses indicated that they were somatosympathetic reflexes and not dorsal root reflexes. (5) The early reflexes remained and the late reflex disappeared on subsequent complete transection of the spinal cord. The early reflexes were therefore spinal reflexes, and suppressed in the animal with cord intact. (6) Lesions at C4, which included a contralateral hemisection and a section of dorsal columns extending into the dorsal part of the lateral funiculus, abolished the inhibition of a sympathetic reflex that followed stimulation of some somatic afferent nerve fibres. These sections did not release the spinal reflex. Therefore, this reflex inhibition was not responsible for the suppression of the spinal somatosympathetic reflex. (7) The descending inhibitory influence on the segmental reflex pathway was not antagonized by strychnine, bicuculline or picrotoxin. (8) The possibility is discussed that the spinal reflex pathway into cardiac sympathetic nerves is tonically inhibited by a bulbospinal pathway originating from the classical depressor region of the ventromedial reticular formation.     

Long latency response of the mentalis muscle following transcranial magnetic stimulation with a circular coil in normal subjects

Short latency response (SLR), middle latency response and long latency response (LLR) are elicited in facial muscles by transcranial magnetic stimulation. Although it has been said that the LLRs are elicited by the trigeminal nerve stimulation, a trigeminofacial reflex is recorded easily in normal subjects by the electrical stimulation in orbicularis oculi muscles as a blind reflex, but a trigeminal-facial reflex recorded in orbicularis oris, namely a snout reflex, is more difficult to record in normal subjects. The aim of this study is to demonstrate the LLR of lower facial muscles (mentalis muscle) by the transcranial magnetic stimulation, using a circular coil. The transcranial magnetic stimulations were performed over parieto-occipital scalp with frequencies of random and 0.3 Hz in 11 normal subjects and the responses in the mentalis muscle were recorded. The LLR of the mentalis muscle was recorded in all 11 subjects following SLRs. The latency, duration and LLR/SLR ratio were 37.4 msec, 20.3 msec and 9.1%, respectively. The waveform of the LLR varied trial to trial showing habituation with a stimulation of 0.3 Hz. At this time the LLR of the masseter muscle was not recorded following this transmagnetic stimulation. It was suggested that the LLR of the mentalis muscle is recorded by the transcranial magnetic stimulation of the trigeminal nerve with a circular coil. The ease and reliability of their recording make it possible to apply this LLR clinically as well as a blink reflex.     

Nociceptive trigeminocervical reflexes in healthy subjects

ObjectiveElectrical stimulation of the supraorbital trigeminal nerve branch induces trigeminocervical reflex responses (TCRs) in the neck muscles. The purpose of this study was to elicit more nociceptive TCR responses through preferential activation of the nociceptive afferents with a concentric surface electrode.MethodsWe recorded TCRs in 10 healthy subjects using both a standard (sTCR) and a nociceptive (nTCR) concentric surface electrode. We compared the baseline parameters, stimulus intensity/response, recovery, and habituation curves recorded for the two types of electrode, and assessed the effects of local anaesthesia.ResultsCompared with the sTCRs, nTCRs showed a significantly longer latency of the late reflex component, as well as lower pain and higher reflex thresholds. They also showed a different recovery cycle and stimulus intensity/response curve, but similar habituation rate. Local anaesthesia attenuated by 85% the late reflex response to stimulation by the concentric electrode, and by only 15% the response to standard electrode stimulation.ConclusionsThe differences observed stimulating with these two electrode types may be due to their different activation of the afferent fibres.SignificanceIf this study were extended to patients affected by primary headaches, TCR monitoring could emerge as a sensitive tool for detecting changes in nociceptive transmission at the level of trigeminocervical complex.     

An analysis of reflex changes in excitability of phrenic,laryngeal, and intercostal motoneurons

An investigation was carried out in anesthetized cats to ascertain whether self-excitation of phrenic motoneurons is a specific or generalized reflex mechanism for motoneurons allied to respiration. Whereas stimulation of only caudal intercostal nerves evoked discharge of phrenic motoneurons (intercostal-to-phrenic reflex), stimulation of all intercostal nerves elicited discharges in the recurrent laryngeal nerve (intercostal-to-recurrent laryngeal reflex). Weak superior laryngeal nerve stimulation provoked short-latency discharges in the recurrent laryngeal nerve but inhibited on-going inspiratory activity in phrenic and external intercostal motoneurons. In the presence of self-excitation of phrenic motoneurons (phrenophrenic system), there was concomitant excitation of laryngeal motoneurons. In contrast, when self-excitation of laryngeal motoneurons occurred (laryngolaryngeal system) there was concomitant inhibition of inspiratory activity (phrenic and external intercostal motoneurons). Paired shocks delivered to superior laryngeal and intercostal nerves while recording from phrenic, recurrent laryngeal, and intercostal nerves failed to reveal convergent interaction. It is concluded that self-excitation is a generalized reflex mechanism for certain motoneurons allied to respiration.     

Characteristics of sympathetic reflexes evoked by electrical stimulation of phrenic nerve afferents.

In chloralose-anaesthetized cats, sympathetic reflex responses were recorded in left cardiac and renal nerve during stimulation of afferent fibres in the ipsilateral phrenic nerve. In cardiac nerve, a late reflex potential with a mean onset latency of 75.6 +/- 13.8 ms was regularly recorded which, in 20% of the experiments, was preceded by an early, very small reflex component (latency between 35 and 52 ms). In contrast, in renal nerve only a single reflex component after a mean latency of 122.1 +/- 13.1 ms was observed. Bilateral microinjections of the GABA-agonist muscimol into the rostral ventrolateral medulla oblongata resulted in a nearly complete abolition of sympathetic background activity and in an 88% reduction of the late reflex amplitude with only small effects on the latency of the evoked potentials. Under this condition, an early reflex component was never observed to appear. After subsequent high cervical spinalization, the residual small potentials which persisted after bilateral muscimol injections were completely abolished and in cardiac nerve an early reflex potential with a mean latency of 45 +/- 10 ms was observed in all but one experiment. The early reflex was therefore referred to as a spinal reflex component which, however, is suppressed in most animals with an intact neuraxis. In the renal nerve a spinal response was only observed in one experiment after spinalization. The results suggest that sympathetic reflexes evoked by stimulation of phrenic nerve afferent fibres possess similar spinal and supraspinal pathways as previously described for somato-sympathetic and viscero-sympathetic reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Percutaneous magnetic coil stimulation of the phrenic nerve roots and trunk

We describe a technique of percutaneous magnetic coil NO stimulation of the phrenic nerve trunk on one side of the neck and phrenic roots over the upper cervical vertebral column in 10 normal subjects and 2 patients. We were able to obtain compound muscle action potentials (CMAPs) from the diaphragm at two sites (xiphoid process and 7th intercostal space) after stimulation of the phrenic nerve trunk and roots. We noted that the onset latencies after phrenic root stimulation remained fixed despite increasing the stimulus intensity from 50% to 100% and on moving the MC vertically or laterally, suggesting that stimulation of the fastest conducting fibers was occurring at a fixed site, most likely at the intervertebral foramina. Absent responses unilaterally in one and prolonged latencies to diaphragmatic CMAPs in another patient confirmed phrenic neuropathy in these patients.     

Phrenic nerve conduction study in demyelinating neuropathies and open-heart surgery.

OBJECTIVES: The aim of this study was to determine normal values of phrenic nerve conduction (PNC) in healthy individuals; to evaluate the subclinical extent of phrenic nerve involvement in Guillain-Barré syndrome (G-B) and hereditary motor and sensory neuropathy-I (HMSN-I), and to evaluate phrenic nerve damage after cardiac surgery. MATERIALS AND METHODS: PNC was performed by transcutaneous stimulation in the neck and recording the diaphragmatic potential from surface electrodes placed at the seventh and eight intercostal spaces. PNC was performed bilaterally in 25 healthy volunteers and 25 patients before and after open-heart surgery. Right PNC was also performed in 5 cases with G-B and 5 patients with HMNS-I. RESULTS: Latency and amplitude of the diaphragmatic potential were the same in controls and in patients with cardiac disease before surgery. After surgery, 28% of patients had left phrenic nerve inexcitability, and 8% had reduced amplitude of the response. These 9 patients demonstrated elevation of the left hemidiaphragm on chest radiography. Left PNC performed 1 year after the operation showed improvement in latency and amplitude of the responses in all except one patient. PNC was prolonged in 4 out of 5 cases with G-B and in all patients with HMNS-I. CONCLUSIONS: PNC is an easy and reliable method in evaluating phrenic nerve damage due to hypothermia or primary stretch injury in patients after cardiac surgery. PNC may be helpful in detecting diaphragmatic involvement before clinical ventilatory insufficiency in demyelinating neuropathies such as G-B and HMNS-I.     

Long-latency reflexes in patients with Behçet's disease

Objective: Recent studies demonstrate that the subclinical involvement of motor pathways is frequently observed in patients with Behçet's disease (BD). Long-latency reflexes (LLR) provide information about the continuity of both ascending and descending neural pathways. Our aim was to evaluate the utility of LLR and somatosensory-evoked potentials (SEP) in demonstrating subclinical neural involvement in patients with BD. Methods: Twenty-nine patients with BD were studied by means of SEP and LLR. Bilateral median nerve SEPs and LLRs evoked by electrical stimulation of both median nerves were recorded. The latency of second component of LLR (LLR2), the duration of LLR2–HR (Hoffmann reflex, spinal reflex component of LLR) interval, peak to peak amplitude of LLR2 and the amplitude ratio of LLR2/HR were analyzed. The data obtained from patients were compared with those of 20 control subjects. Results: LLR2 latencies and the durations of LLR2–HR interval were significantly prolonged in patients with BD (p=0.001 for both parameters). Increased duration of LLR2–HR interval was the most frequent abnormality observed in the study (37.9%). Conclusion: Our findings suggest that LLR is a useful technique to demonstrate subclinical neural involvement in patients with BD.     

Phrenic Nerve Stimulation for Diaphragm Pacing in a Quadriplegic Patient

Chronic hypoventilation due to injury to the brain stem respiratory center or high cervical cord (above the C3 level) can result in dependence to prolonged mechanical ventilation with tracheostomy, frequent nosocomial pneumonia, and prolonged hospitalization. Diaphragm pacing through electrical stimulation of the phrenic nerve is an established treatment for central hypoventilation syndrome. We performed chronic phrenic nerve stimulation for diaphragm pacing with the spinal cord stimulator for pain control in a quadriplegic patient with central apnea due to complete spinal cord injury at the level of C2 from cervical epidural hematoma. After diaphragmatic pacing, the patient who was completely dependent on the mechanical ventilator could ambulate up to three hours every day without aid of mechanical ventilation during the 12 months of follow-up. Diaphragm pacing through unilateral phrenic nerve stimulation with spinal cord stimulator was feasible in an apneic patient with complete quadriplegia who was completely dependent on mechanical ventilation. Diaphragm pacing with the spinal cord stimulator is feasible and effective for the treatment of the central hypoventilation syndrome.     

Correlation between somatosensory evoked potentials and long loop reflexes--basic investigation and its application for multiple sclerosis

Somatosensory evoked potentials (SEPs) and long loop reflexes (LLRs) to the median nerve stimulation were investigated on 25 normal controls and 25 patients with multiple sclerosis (MS). Fifteen normal controls were also subjected to LLR study by the common peroneal nerve stimulation. The mean height were 159 +/- 8.2 cm in normal controls and 160 +/- 8.9 cm in MS, respectively. LLRs were obtained with 100% reproducibility in all cases. Upper limb LLRs were recorded from m. abductor pollicis brevis by trigger stimulation during isotonic contraction of the thumb, while lower limb LLRs were recorded from m. peroneus longus by trigger stimulation during isotonic eversion of the foot. The threshold of LLR was lower than that of short latency reflex (H-wave) with the mean latency of 40.4 +/- 1.5 ms. The height of subjects revealed an obvious positive correlation not only with the latency of LLR but also with N 20 of SEP, whereas central conduction time was not. Furthermore, a significant correlation was present between the latencies of LLR and N 20, showing a twofold gradient of LLR against N20. There was a significantly prolonged latency difference between H-wave and LLR of lower limb as compared with that of upper limb. When the stimulation site was changed from the wrist to the elbow, the latency difference between M-wave and H-wave shortened. This fact, therefore, appears to be against "resonance hypothesis" that LLR is set off according to the intrinsic mechanical oscillation given to the muscle concerned.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phrenic nerve neurotization utilizing the spinal accessory nerve: technical note with potential application in patients with high cervical quadriplegia

Introduction  High cervical quadriplegia is associated with high morbidity and mortality. Artificial respiration in these patients carries significant long-term risks such as infection, atelectasis, and respiratory failure. As phrenic nerve pacing has been proven to free many of these patients from ventilatory dependency, we hypothesized that neurotization of the phrenic nerve with the spinal accessory nerve (SAN) may offer one potential alternative to phrenic nerve stimulation via pacing and may be more efficacious and longer lasting without the complications of an implantable device. Materials and methods  Ten cadavers (20 sides) underwent exposure of the cervical phrenic nerve and the SAN in the posterior cervical triangle. The SAN was split into anterior and posterior halves and the anterior half transposed to the ipsilateral phrenic nerve as it crossed the anterior scalene muscle. Results  The mean distance between the cervical phrenic nerve and the SAN in the posterior cervical triangle was 2.5 cm proximally, 4 cm at a midpoint, and 6 cm distally. The range for these measurements was 2 to 4 cm, 3.5 to 5 cm, and 4 to 8.5 cm, respectively. The mean excess length of SAN available after transposition to the more anteromedially placed phrenic nerve was 5 cm (range 4 to 6.5 cm). The mean diameter of these regional parts of the spinal accessory and phrenic nerves was 2 and 2.5 mm, respectively. No statistically significant difference was found for measurements between sides. Conclusions  To our knowledge, using the SAN for neurotization to the phrenic nerve for potential use in patients with spinal cord injury has not been previously explored. Following clinical trials, these data may provide a mechanism for self stimulation of the diaphragm and obviate phrenic nerve pacing in patients with high cervical quadriplegia. Our study found that such a maneuver is technically feasible in the cadaver.     

Phrenic nerve conduction in infancy and early childhood

Diaphragmatic action potentials (DAPs) were mapped on the thorax bilaterally in 16 neurologically normal infants and 8 boys aged 1 to 4 years during artificial ventilation after thoracic surgery. Transcutaneous stimulation was used to activate the phrenic nerve at the supraclavicular fossa at the end of an artificial inspiration. The DAPs were of positive polarity and were recorded on the ipsilateral anterolateral chest wall over the sixth to the eighth intercostal spaces, with a maximal peak at the seventh intercostal space. The DAP latencies gradually decreased from 6 to 8 ms at birth to about 5 ms at the age of 1 year, despite an increase of conduction distance. Statistical analyses revealed that DAP amplitude did not correlate with age. The latencies and amplitudes of the DAPs displayed little interside variation. The results are valuable not only as a reference for the diagnosis of patients with phrenic nerve palsy, but also as an indicator of the normal development of the phrenic nerve.     

Neurophysiologic markers in laryngeal muscles indicate functional anatomy of laryngeal primary motor cortex and premotor cortex in the caudal opercular part of inferior frontal gyrus

ObjectiveThe aim of this study was to identify neurophysiologic markers generated by primary motor and premotor cortex for laryngeal muscles, recorded from laryngeal muscle.MethodsTen right-handed healthy subjects underwent navigated transcranial magnetic stimulation (nTMS) and 18 patients underwent direct cortical stimulation (DCS) over the left hemisphere, while recording neurophysiologic markers, short latency response (SLR) and long latency response (LLR) from cricothyroid muscle. Both healthy subjects and patients were engaged in the visual object-naming task. In healthy subjects, the stimulation was time-locked at 10–300 ms after picture presentation while in the patients it was at zero time.ResultsThe latency of SLR in healthy subjects was 12.66 ± 1.09 ms and in patients 12.67 ± 1.23 ms. The latency of LLR in healthy subjects was 58.5 ± 5.9 ms, while in patients 54.25 ± 3.69 ms. SLR elicited by the stimulation of M1 for laryngeal muscles corresponded to induced dysarthria, while LLR elicited by stimulation of the premotor cortex in the caudal opercular part of inferior frontal gyrus, recorded from laryngeal muscle, corresponded to speech arrest in patients and speech arrest and/or language disturbances in healthy subjects.ConclusionIn both groups, SLR indicated location of M1 for laryngeal muscles, and LLR location of premotor cortex in the caudal opercular part of inferior frontal gyrus, recorded from laryngeal muscle, while stimulation of these areas in the dominant hemisphere induced transient speech disruptions.SignificanceDescribed methodology can be used in preoperative mapping, and it is expected to facilitate surgical planning and intraoperative mapping, preserving these areas from injuries.     

Serotonergic modulation of spinal ascending activity and sacral reflex activity evoked by pelvic nerve stimulation in cats

Serotonin (5-HT) may be inhibitory to micturition at a spinal level. A potential mechanism of action for serotonergic inhibition of bladder function is a depression of the ascending limb of the supraspinal reflex mediating micturition. Ascending activity evoked by pelvic nerve stimulation was recorded in the thoracic spinal cord of anesthetized cats. For comparison, spinal reflex activity evoked by pelvic nerve stimulation was recorded on the pudendal nerve. The effects of intrathecal administration of serotonergic agents were examined to determine whether spinal and supraspinal responses to bladder afferent activation were modulated by 5-HT. Methysergide (60 nmol), a non-selective serotonergic antagonist, increased ascending activity by 61±7% and depressed spinal reflex activity by 38±6%. Zatosetron (10 nmol), a 5-HT₃ antagonist had a similar effect on both activities (increased by 93±24% and decreased by 77±7%, respectively). The effect on ascending activity of blocking 5-HT₃ receptors was also confirmed with ICS 205930 and MDL 72222. 2-Methyl-5-HT (800 nmol), a 5-HT₃ agonist, depressed ascending activity to 46±9% of control, but enhanced spinal reflex activity by 73±92%. These results demonstrate that stimulation of 5-HT₃ and methysergide-sensitive 5-HT receptors can inhibit ascending activity and facilitate spinal reflex activity elicited by activation of bladder afferents. It is suggested that descending serotonergic pathways may participate in the spinal coordination of urinary continence.     

Transient phrenic nerve palsy after cardiac operation in infants.

OBJECTIVE: The aims of this study were to prove the presence of transient phrenic nerve palsy in children after cardiac surgery by successive recordings of diaphragmatic action potentials (DAPs), and to decide the indication of diaphragmatic plication in infants with postoperative phrenic nerve palsy. METHODS: The DAPs were recorded from 11 infants (age 0-54 months) under artificial ventilation after cardiac surgery. The successive DAP recordings were performed within 3-4 days (0W), 1 week (1W) and 2 weeks (2W) after operation to make a final decision for diaphragmatic plication to wean artificial ventilation. RESULTS: The patients were divided into 3 groups according to the DAP changes in successive recordings, namely, patients with normal DAPs at 0W, patients with transient depression of DAPs at 0W followed by recovery to normal DAPs by 1W and/or 2W, and patients with persistent depression of DAPs of the affected side necessitating plication of hemidiaphragm. CONCLUSIONS: In infants with phrenic nerve palsy after cardiothoracic surgery, persistently abnormal DAPs in repeated electrophysiologic examinations for at least 2 weeks after surgery are a useful guidance to support clinical and radiological evidence for an indication of diaphragmatic plication.     

Contralateral diaphragmatic palsy after subcortical middle cerebral artery infarction without capsular involvement

Diaphragmatic palsy after acute stroke is a novel clinical entity and may result in a high incidence of respiratory dysfunction and pneumonia, which especially cause greater morbidity and mortality. Generally, internal capsule and complete middle cerebral artery (MCA) infarctions are major risk-factors for developing diaphragmatic palsy. Herein, we present a case with contralateral diaphragmatic palsy after a subcortical MCA infarction without capsular involvement. Dyspnea occurred after stroke, while a chest X-ray and CT study disclosed an elevated right hemidiaphragm without significant infiltration or patch of pneumonia. A phrenic nerve conduction study showed bilateral mild prolonged onset-latency without any significant right–left difference. This suggested a lesion causing diaphragmatic palsy was not in the phrenic nerve itself, but could possibly originate from an above central location (subcortical MCA infarction). We also discussed the role of transcranial magnetic stimulation study in the survey of central pathway and demonstrated diaphragmatic palsy-related orthopnea.     

The n10 component of the ocular vestibular-evoked myogenic potential (oVEMP) is distinct from the R1 component of the blink reflex

ObjectiveBone-conducted vibration (BCV) in the midline at the hairline (Fz), results in short latency potentials recorded by surface electrodes beneath the eyes – the ocular vestibular-evoked myogenic potential (oVEMP). The early negative component of the oVEMP, n10, is due to vestibular stimulation, however it is similar to the early R1 component of the blink reflex. Here we seek to dissociate n10 from R1.MethodsSurface potentials were recorded from the infraorbital electromyogram of 10 healthy subjects, 6 patients with bilateral vestibular loss, 2 with unilateral vestibular loss, 4 with facial palsy and 3 with facial and vestibular nerve lesions on the same side. BCV was delivered at Fz, the inion, the glabella or the supraorbital ridge using a tendon hammer or a bone-conduction vibrator.ResultsOnset latencies of the n10 evoked by taps at Fz or inion were significantly shorter than the R1 components of blink responses to supraorbital and glabellar stimuli. Upward gaze increased the amplitude of n10 but not R1. The n10 was absent bilaterally in patients with bilateral vestibular loss and beneath the contralesional eye in patients with unilateral vestibular loss, but in both these groups of patients R1 was preserved. In severe facial palsy the R1 component was absent or delayed and attenuated ipsilesionally, but n10 was preserved bilaterally. In subjects with unilateral facial and vestibular nerve lesions (Herpes Zoster of the facial and vestibulocochlear nerves) the dissociation was complete – the ipsilesional R1 was absent or attenuated whereas the ipsilesional n10 was preserved.Conclusionsn10 is distinguished from R1 by its earlier onset, laterality, modulation by gaze position and dissociation in patient groups.SignificanceThe n10 component evoked by BCV at Fz is not the R1 component of the blink reflex.