Pre-operative embolization and excision of vagal schwannoma with rich vascular supply: A case report and literature review.

RATIONALE: Schwannomas are benign tumors wrapped in the nerve sheath and can originate from the myelin sheath of the cranial nerve. In previous literature reports, most of the tumors were solid tumors, which can be removed only by surgery. This case report describes a unique case of vagal schwannoma, which, unlike previous cases, involves a dominant arterial supply, and discusses the pre-operative evaluation, relevant radiographic findings, and surgical process of the case in detail. PATIENT CONCERNS: A 31-year-old woman sought treatment for pain in the left side of the neck when turning her head. A mass on the left side of the neck was found on enhanced computed tomography with a maximum diameter of 6.8 cm, along with multiple tortuous, thickened vascular shadows, and pressure on the left pharyngeal cavity. DIAGNOSIS: The pathological results showed schwannoma. INTERVENTIONS: Considering the unusual size of the tumor and thickened blood vessels revealed by pre-operative computed tomography, general anesthesia and biopsy were conducted first to confirm the diagnosis. Excessive bleeding occurred during the process; thus, the tumor was only partially removed before the wound closed after hemostasis. Digital subtraction angiography indicated that the tumor was supplied by multiple arteries, and the tumor was removed by pre-operative embolization plus intra-operative removal. OUTCOMES: Combined with embolization and surgical resection, the tumor was completely removed, the nerve was partially preserved, and the patient had postoperative hoarseness. LESSON: The present case indicates the possibility of vascularly supplied vagal schwannoma; thus, it is necessary to conduct pre-operative digital subtraction angiography.

Cervical vagus nerve morphometry and vascularity in the context of nerve stimulation - A cadaveric study.

Vagus nerve stimulation (VNS) has become a well-established therapy for epilepsy and depression, and is emerging to treat inflammatory disease, with the cervical vagus nerve (CVN) as major stimulation site. CVN morphometries are missing for VNS, considering its variability. Morphometric data were obtained from CVNs in 27 cadavers, including branching patterns and histology. Cross-sectional area, greater and lesser diameters averaged 7.2 ± 3.1 mm2, 5.1 ± 1.5 and 4.1 ± 1.3 mm, and were ≤11.0 mm2, ≤7.0 and ≤5.8 mm in 90% of the specimens, respectively. Midline distance (position lateral to the laryngeal eminence) and skin distance (anterior-posterior from skin) averaged 34.5 ± 6.2 and 36.2 ± 9.4 mm, ≤49.0 and ≤41.0 mm in 90%, respectively. Nerve dimensions and surface topography correlated closely, but without gender-, side- or branching-dependent differences. The nerve fascicle number averaged 5.2 ± 3.5. Vagal arteries were observed in 49% of the cases. Negative correlations were found for age and cross-sectional area, as well as subperineural vessel count. Detailed anatomical data on the CVN and its vascularity are given, forming the morphometric basis for VNS refinement, filling an evident gap in light of the CVN being a structure with variable positions and branching. A 35 × 35-mm rule may apply for the CVN position, irrespective of branching or positional variation.

Positional Relations of the Cervical Vagus Nerve Revisited.

OBJECTIVES: The cervical part of the vagus nerve (CVN) has become an important target for stimulation therapy to treat epilepsy and psychiatric conditions. For this purpose, the CVN is visualized in the carotid sheath, assuming it to be localized dorsomedially between the carotid artery (CA) and the internal jugular vein (JV). The aim of our morphological study was therefore to revisit the CVN relationships to the CA and JV, hypothesizing it to have common variations to this classical textbook anatomy. MATERIALS AND METHODS: Positional relations of the CVN, CA and JV were investigated in the carotid sheath of 35 cadavers at the C3 to C6 level. Positional relations of the CVN, CA and JV were documented on the basis of a 3 × 3 chart. RESULTS: Eighteen different arrangements of the CVN, CA and JV were observed. The typical topographic relationship of the CVN dorsomedially between the CA and JV was only found in 42% of all cases. The CVN was located dorsally or (dorso-)laterally to the CA in 80% and dorsally or (dorso-)medially of the JV in 96% of all cases. CONCLUSIONS: Classical textbook anatomy of the CVN is only present in a minority of cases. Positional variations in contrast to textbook anatomy are considerably more frequent than previously described, which might be a hypothetical morphological explanation for the lack of efficacy or side effects of CVN stimulation. Furthermore, the position of the CVN relative to the internal jugular vein is more consistent than to the CA.

Ischemic vagus nuclei lesions and hyperglycemia: a study in 26 patients with lateral medullary infarction and matched controls.

BACKGROUND: Hyperglycemia is common after stroke in diabetic and nondiabetic patients. Furthermore, it has been associated with infarct expansion, worse functional outcomes and higher mortality. In a previous study, infarction of the insular region was related to higher poststroke glucose levels than infarcts in other cortical areas. Experimental studies in animal models suggested that the lower brainstem nuclei of the vagus nerve modulate insulin secretion. These nuclei are usually affected in lateral medullary infarction (LMI). We evaluated whether patients with lateral medullary stroke have worse poststroke glycemic control than other stroke patients. METHODS: A hospital-based stroke registry was used to identify 26 patients from the years 2000 to 2010 who fulfilled the following inclusion criteria: (1) a first-ever stroke; (2) neurological deficits compatible with LMI; (3) MRI confirmation of an ischemic lesion of the lateral medulla involving the vagus nerve nuclei, and (4) no simultaneous infarcts. Patients were excluded if they were admitted to the hospital more than 24 h after stroke onset or died in the first 24 h after hospital admission. A control group of other stroke patients was randomly selected from the same stroke registry and over the same time period, matching for the age and gender of the LMI group. The average glycemia was compared between the two groups using a linear regression model adjusted for confounders. Glycated hemoglobin at admission was used to estimate prestroke glycemic control. Prestroke glycemic averages were then compared with poststroke glycemia for the two groups using the Wilcoxon signed test for related samples. RESULTS: The average glycemia of the LMI patients in the first 24 h after stroke was 9.4 mmol/l (SD 3.2), and from 24 to 72 h it was 7.6 mmol/l (SD 2.8). In the comparison group, these values were 7.7 (SD 2.8) and 7.1 mmol/l (SD 2.7), respectively. As expected, diabetic patients had a significantly higher glycemia than nondiabetic patients (p < 0.0001). The adjusted linear regression model showed the average glycemia differences to be significant for the first 24 h (p = 0.001; R(2) = 55.6%) but not for the 24- 72 h period. The frequency of previous diabetes mellitus was similar in both groups. As compared to prestroke glycemic estimates, glycemia in lateral medullary stroke patients increased significantly more than in controls during the first 24 h after stroke (p = 0.01), but again there were no significant differences for the 24-72 h period. CONCLUSIONS: This study suggests that ischemic lesions of the vagus nerve nuclei are associated with worse early poststroke glycemic control than stroke in other locations. Confirmation of this hypothesis and the long-term implications of glucose control impairment warrant further prospective studies.

Medullary microvessel degeneration in multiple system atrophy.

Multiple system atrophy (MSA) is a rare and fatal early-onset autonomic disorder which is characterised by Parkinsonism and orthostatic hypotension (OH). The pathophysiology of MSA is not fully understood but key features include the depletion of medullary autonomic neurons and presence of glial cellular inclusions. We hypothesise that the degeneration of medullary autonomic microvessels is an additional finding in MSA. Using digital pathology we quantified basement membrane collagen (Coll IV), smooth muscle actin (alpha-actin) and endothelial glucose transporter (Glut 1) expression in medullary autonomic nuclei of 8 MSA and 8 OH cases, compared with 12 controls with no autonomic dysfunction. We found decreased Coll IV (p=0.000) and Glut 1 (p=0.000) but not alpha-actin expression, in medullary autonomic nuclei of MSA, but not OH cases compared with control subjects. Medullary microvessel degeneration in MSA may be secondary to the primary neuro-glial pathogenesis of the disorder, and could accelerate its ageing-related progression.

Management of cervical paragangliomas: review of a 15-year experience.

BACKGROUND AND AIMS: Cervical paragangliomas are highly vascular neoplasms and should be considered in the evaluation of all lateral neck masses. The aim of this study is to review an institutional experience in the management of these tumors. MATERIALS AND METHODS: Thirteen patients with 14 paragangliomas were treated in our institution during a period of 15 years. There were eight women (61.5%) and five men (38.5%) with a mean age of 41.3+/-15 years. A painless lateral neck mass was the main finding in 69.2% of patients. There was no evidence of a functional tumor. Carotid angiography was performed in all patients to define the vascular anatomy of the lesion. The 78.6% of paragangliomas underwent selective embolization of the major feeding arteries. Surgical resection followed within the next 48 h. RESULTS: The majority of the lesions were paragangliomas of the carotid bifurcation (85.7%), while one patient was diagnosed with a jugular and one with a vagal paraganglioma. In one patient, bilateral paragangliomas in the carotid bifurcation were detected. There was no evidence of malignancy in any case. Preoperative embolization has proven successful in reducing tumor vascularity. Vascular reconstruction was necessary in one patient. The main postoperative complication was transient cranial nerve deficit in seven (53.8%) patients, and a permanent Horner's syndrome was documented in one patient. No stroke occurred. The jugular paraganglioma was treated with irradiation due to skull base extension with significant symptomatic relief. CONCLUSION: Combined therapeutic approach with preoperative selective embolization followed by surgical resection by an experienced team offers a safe and effective method for complete excision of the tumors with a reduced morbidity rate.

Cardiac vagal outflow after aerobic training by analysis of high-frequency oscillation of the R-R interval.

This study was designed to assess the effect of aerobic training on the dynamics between the R-R interval length and the high-frequency (HF) oscillation of the R-R interval. Seventeen healthy males (26+/-2 years) participated in an 8-week aerobic training intervention. The mean HF spectral power (0.15-0.4 Hz) of the R-R interval and the mean R-R interval length were analyzed from 24-h recordings. HF power was also analyzed in 5-min sequences and plotted as a function of the corresponding mean R-R interval length. The relationship between the R-R interval length and the HF power was analyzed by a quadratic regression model. The relationship was defined as saturated if the distinct deflection point of the model occurred before the maximum R-R interval. Otherwise, the relationship was defined as linear. Additionally, the mean HF power was calculated from the linear portion of the R-R interval versus the HF power regression curve (HF index). Before the training intervention, seven subjects had a saturated HF power. After the intervention, five new cases of saturated HF power were observed. The mean HF power of the 24-h recording did not change in the group with a saturated HF power before training (7.4+/-0.8 vs. 7.6+/-0.8 ms(2)), but the HF index increased (6.7+/-0.7 vs. 7.1+/-0.7 ms(2), P<0.05). We conclude that enhanced vagal activity due to aerobic training increases the prevalence of the saturation of the HF oscillation of the R-R interval variability in healthy subjects. HF power calculated from unsaturated area detects more accurately subtle changes in the vagally mediated beat-to-beat variability of the R-R interval after aerobic training than the mean 24-h HF power.

Intrathoracic blood supply of the left vagus and recurrent laryngeal nerves.

The arteries and veins of the left vagus (VN) and left recurrent laryngeal (RLN) nerves from the thoracic inlet to the subaortic region are described following vascular casting with red colored latex in 6 adult fresh non-embalmed cadavers. In all specimens the anterior bronchoesophageal artery supplied at least one vessel to the VN and RLN in the subaortic region. For the RLN other arterial sources were arteries arising from the aortic arch in 1 specimen, the subclavian artery in 3 specimens, the first intercostal artery in 1 specimen, and the inferior thyroid artery in all specimens. For the VN other arterial sources were arteries arising from the aortic arch in 2 specimens and the inferior thyroid artery in 1 specimen. For both the VN and RLN the veins were located under the pleura and directed towards the internal thoracic vein anteriorly and the thoracic intercostal veins posteriorly. In conclusion, the inferior thyroid artery at the thoracic inlet for the RLN and the anterior bronchoesophageal artery are the more consistent vessels supplying the VN and RLN. Vascular damage occurring during mediastinal lymph node excision to the VN and RLN, especially in the subaortic region, may explain postoperative vocal fold paralysis.

Effects of aging and cardiac denervation on heart rate variability during sleep.

BACKGROUND: Cardiac vagal predominance increases the RR interval and RR high-frequency (HF) variability during non-rapid eye movement (non-REM) sleep (stages I through IV) in young subjects. Aging suppresses deep sleep, but effects of age-related changes in sleep architecture on RR are unknown. Whether mechanical effects of changes in the breathing pattern on the sinus node during sleep affect RR variability is unclear. METHODS AND RESULTS: Polygraphic sleep recordings and RR and RR spectral profiles were determined in 8 young (22.5+/-3.3 years) and 8 older (55.0+/-7.3 years) healthy volunteers. HF oscillations in RR of 8 cardiac-denervated heart transplant recipients determined mechanical effects of respiration on the sinoatrial node during sleep. Transition from wakefulness to non-REM sleep increased the RR interval in young and older subjects and increased the HF variability of RR in the young (P:<0.05) but not in the older subjects. Older subjects disclosed a faster RR (P:<0.01) and a lower HF variability (P:<0.05) during non-REM sleep than the young subjects. Aging did not affect light and REM sleep but decreased deep sleep (stage IV) from 39+/-23 to 6+/-6 minutes (P:<0.001). Reduction in sleep stage IV with aging blunted the increase in RR and in RR HF variability during non-REM sleep (r>0.55, P:<0.05). Transition from wakefulness to non-REM sleep doubled the markedly reduced HF variability of RR in the heart transplant recipients (P:<0.05). CONCLUSIONS: Disappearance of deep sleep with aging impairs nocturnal increase in cardiac vagal activity. Mechanical effects of changes in breathing pattern during sleep favor increases in HF oscillations of the RR interval during non-REM sleep.

Anatomy and blood supply of the lower four cranial and cervical nerves: relevance to surgical neck dissection.

This study is a continuation of previous work searching for possible anatomic reasons to explain variable and usually unpredictable postoperative pain and dysfunction after the same nerve losses with similar neck dissection operations. The study consisted of dissections of 19 deceased unpreserved elderly subjects arterially injected with dyed latex. Of the 19 subjects, 14 had brain stem and cervical spinal cord dissections, and all had neck dissections. The findings suggested two possible anatomic reasons for the pain and dysfunction: (i) The intracranial anatomy of the lower four cranial nerves, the glossopharyngeal (IX), the vagus (X), the spinal accessory (XI), and the hypoglossal (XII), was just as variable as the previously reported peripheral spinal accessory nerve plexus; and (ii) Both the intracranial and neck dissections indicated that the blood supply to the lower four cranial and cervical nerves, particularly to the brachial plexus, could be impaired by atherosclerosis and/or neuroforaminal impingement or operative loss. This loss of blood supply theoretically could result in ischemia as another possible cause of postoperative pain and dysfunction. It is concluded that because of the potential importance of each nerve and vessel, often unknown at operation, it is very important to spare as many of them as possible to avoid subsequent painful impairment.

Recurrent laryngeal nerve dysfunction following carotid endarterectomy.

Recurrent laryngeal nerve dysfunction is a significant complication of carotid endarterectomy and vocal cord paralysis is a major source of morbidity. This study prospectively assessed patients undergoing carotid endarterectomy to determine the nature and frequency of vocal cord damage and attempt to identify avoidable factors. Fifty consecutive patients undergoing carotid endarterectomy for symptomatic disease were studied. A standardized surgical technique was used emphasizing identification of the vagus nerve and minimal disturbance of the surrounding tissues. All patients underwent pre-operative and post-operative (day 2) indirect laryngoscopy and videostroboscopy. Pre-operative assessment found asymptomatic compensated vocal cord paralysis in one patient who had previously had a stroke. Post-operative laryngoscopy revealed asymptomatic impaired vocal cord mobility in three patients (6%) all of whom recovered completely. In addition six patients (12%) developed post-operative hoarseness of whom five have fully recovered. The remaining patient (2%) developed vocal cord paralysis which is permanent to date. This prospective study demonstrates that recurrent laryngeal nerve dysfunction is a common but often transient complication of carotid endarterectomy. The incidence of vocal cord paralysis in this group was less than many of the reported series. This could be due to the technique of minimal dissection which may prevent disturbance of the vagal segmental blood supply. Pre-operative vocal cord assessment is essential in all patients undergoing carotid endarterectomy.

Neurovascular compression at the left ventrolateral medulla as an etiological factor for arterial hypertension.

Clinical studies by Jannetta and others implicated that arterial compression of the root entry zone (REZ) of cranial nerves IX and X at the left ventrolateral medulla may represent an etiological factor for arterial hypertension. Positive therapeutic outcomes with reduction of hypertension in 42 of Jannetta's patients by microsurgical decompression initiated further studies. Experience of our group points in the same direction. Four patients treated by microvascular decompression showed lasting reduction of severe hypertension postoperatively. In our previous comparing postmortem explorations and angiographic studies essential hypertensive patients displayed signs of left sided neurovascular compression in opposition to normotone controls or renal hypertensive patients. By using MR-imaging we are currently developing a method of detecting neurovascular compression syndromes in hypertensive patients suitable for surgical management.

MR screening for brain stem compression in hypertension.

PURPOSE: To determine the clinical usefulness of MR imaging to screen for vascular compression of the lateral medulla, considered by some to be responsible for neurogenic hypertension. METHODS: MR images and clinical records of 120 adults who had received brain MR imaging for any reason were divided into two groups: group 1 (n = 60) consisted of patients with essential hypertension and group 2 (n = 60) included patients who lacked a diagnosis of hypertension. No patient manifested symptomatic cranial neuralgias. The root entry zone of cranial nerves IX and X into the left lateral medulla was examined by MR imaging for proximity to the ipsilateral vertebral artery or its branches. Images lacking any contact between visible vascular structures and the root entry zone were recorded as normal. Vascular compression was graded according to the degree of proximity to the root entry zone. Lateral medullary contact only (grade I), contact and depression (grade II), or lower brain stem displacement or rotation (grade III) of the root entry zone were recorded in both hypertensive and normotensive patients. Among hypertensive patients, additional data were gathered from electrocardiographic, echocardiographic, and urinary protein reports. RESULTS: We found compression in 34 (57%) of the patients from group 1 and in 33 (55%) of the patients from group 2. Compressions in group 1 were grade I in 22 (37%) of the patients, grade II in 8 (45%), grade II in 4 (7%), and grade III in 2 (3%). There were no statistically significant differences in MR findings between the two groups. Among group 1 patients, MR grading did not predict end-organ changes in the heart (left axis deviation and left ventricular hypertrophy) or kidneys (proteinuria). CONCLUSION: Vascular compression of the root entry zone of cranial nerves IX and X into the left lateral medulla is not an adequate lesion to produce systemic hypertension. This finding is as common among normotensive patients as among hypertensive populations. Neither the presence nor the severity of changes in the root entry zone on MR images increases the occurrence of common end-organ responses in the heart or kidneys among hypertensive patients. MR screening is not warranted among hypertensive patients lacking symptomatic cranial neuralgias.

The blood supply of vagus nerve in the human: its implication in carotid endarterectomy, thyroidectomy and carotid arch aneurectomy.

The human vagus nerve is supplied by a distinct vagal artery and vein. The artery, which lies on the anterior aspect of the nerve, is reinforced by many small arterioles along its course. These small vessels often lie in the surgical fields in carotid endarterectomy, thyroidectomy and aortic arch aneurectomy. Damage to these vessels may damage the vagus nerve and account for inexplicable cases of vagal palsy following the above surgical procedures.

Preoperative embolization for paraganglioma.

We have applied a new method of preoperative embolization to an intravagal and to carotid body paraganglioma, using estrogen dissolved in absolute alcohol and polyvinyl alcohol particles, which diffusely embolizes vessels from capillaries to main feeders. Total resection of the tumors after embolization was successively performed without postoperative complications; total blood loss was 205 and 130 ml, respectively, and the surgical time was approximately 3 hours in both cases. The technique, characteristics, and advantages of this method are discussed.

Innervation of epi- and endoneurial compartments of rat facial, vagus and sciatic nerves as studied by double-labeling immunofluorescence.

The mediators of axon terminals innervating the blood vessels and connective tissue compartments of rat peripheral nerves (facial, vagus and sciatic nerve) were investigated by means of double-labeling immunofluorescence. Sympathetic noradrenergic/neuropeptide-Y-immunoreactive axons innervated epi- and endoneurial arterial blood vessels; noradrenergic fibers without neuropeptide Y immunoreactivity terminated in the endoneurium between the axons of the main nerve trunk. Presumably sensory nerve terminals immunoreactive to substance P/calcitonin gene-related peptide supplied epi- but not endoneurial arteries and arterioles, and ran freely in the endoneurial space. Axons immunoreactive to vasoactive intestinal peptide innervated epineurial blood vessels of the facial and vagus nerve but were absent from the vasa nervorum of the sciatic nerve. The findings are in line with the concept, based upon previous pharmacological experiments, of a tonic constrictory and dilatory innervation of vasa nervorum. However, as judged from the distribution patterns of the neurochemically distinct axonal populations, vascular segments of different connective tissue compartments (epi- versus endoneurial) and body regions (sciatic versus cranial nerves) are differentially addressed by each of these axonal populations. This might have implications for the development of region-specific neuropathies.

[Unilateral paralysis of the glossopharyngeal, vagus and hypoglossal nerves]. / Paralysie unilatérale des nerfs glossopharyngien, vague et grand hypoglosse.

A 32-year-old woman complained of swallowing difficulty after a general seizure. Neurological examination revealed unilateral palsies of the 9th, 10th, and 12th cranial nerves. CT, MRI and internal carotid artery angiogram were normal. Selective catheterization of the external carotid artery and ascending pharyngeal system suggested a cranial nerve ischaemic arterial syndrome. The apparent sparing of the eleventh nerve may be explained by the double vascularization of this nerve. This may also be related to the double innervation of the trapezius and sterno-cleido-mastoid muscles by the 11th nerve and cervical spinal nerves.

Neurovascular relationships of the root entry zone of lower cranial nerves: a microsurgical anatomic study in fresh cadavers.

The study describes the microsurgical neurovascular relationships of the root entry zone of lower cranial nerves in 23 cadavers. The vessel type, frequency of contact and site of contact on the root entry zone were analysed. Three types of vascular patterns (Types I-III) were found. Facial nerve: frequency of contact 31.8%; arterial contact 92.9%, Type I (lying across) 78.9%; anterior inferior cerebellar artery in 84.6%. Glossopharyngeal nerve: frequency of contact 23.9%; arteries 54.5%, veins 45.5%; posterior inferior cerebellar artery in 83.3% and Type II (loop) 50.1%. Vagus nerve: frequency of contact 26.1%, arteries 58.3%. Types II and III (passing through) formed 42.9% each. Hypoglossal nerve: frequency of contact 78.2%; vertebral artery 88.9%. No 'grooving' on any nerve was seen. Hence, 'contact' by a vessel at the root entry zone may not be significant in the etiology of lower cranial rhizopathies.