Duplicated Vagus Nerve in Adolescence: Case Report and Review of Literature.

BACKGROUND: Vagus nerve stimulation (VNS) has become an increasingly popular procedure for the treatment of epilepsy and depression. Significant complications or side effects associated with VNS surgery may result from either the inadvertent direct injury to the vagus nerve as part of the surgical approach, placement of the electrode, or the concomitant stimulation of vagal efferent fibers. To mitigate these effects, the recognition of anatomic variants that may place the nerve at increased risk is necessary. CASE DESCRIPTION: During microsurgical dissection of the carotid sheath for the implantation of a vagus nerve stimulator in a 17-year-old male patient with refractory epilepsy, additional nonidentified nerve tissue was found running parallel to the vagus nerve. These fibers were two thirds of the thickness of the vagus nerve and ran medial to it, from the most superior to the most inferior aspect of the carotid sheath dissection, found at a distance of at least 4 cm in a craniocaudal direction. This duplicated nerve did not appear to branch from the vagal trunk nor exit the sheath but rather paralleled the course of the vagus nerve. The parallel course and the proximity of the unidentified nerve make this structure likely to be a duplicated vagus nerve. CONCLUSIONS: This is the first reported case of cervical vagus nerve duplication presented in the literature. Surgeons performing VNS implantations should be cognizant of this potential anomaly in order to avoid inadvertent injury to the nerve.

Asociación de bronquio traqueal y drenaje venoso pulmonar anómalo parcial en paciente con neurofibromatosis tipo 1 y neurofibroma del nervio vago ipsilateral / Combination of tracheal bronchus and partial anomalous pulmonary venous return in a patient with type 1 neurofibromatosis and ipsilateral vagal nerve neurofibroma

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Sprouty genes are essential for the normal development of epibranchial ganglia in the mouse embryo.

Fibroblast growth factor (FGF) signalling has important roles in the development of the embryonic pharyngeal (branchial) arches, but its effects on innervation of the arches and associated structures have not been studied extensively. We investigated the consequences of deleting two receptor tyrosine kinase (RTK) antagonists of the Sprouty (Spry) gene family on the early development of the branchial nerves. The morphology of the facial, glossopharyngeal and vagus nerves are abnormal in Spry1-/-;Spry2-/- embryos. We identify specific defects in the epibranchial placodes and neural crest, which contribute sensory neurons and glia to these nerves. A dissection of the tissue-specific roles of these genes in branchial nerve development shows that Sprouty gene deletion in the pharyngeal epithelia can affect both placode formation and neural crest fate. However, epithelial-specific gene deletion only results in defects in the facial nerve and not the glossopharyngeal and vagus nerves, suggesting that the facial nerve is most sensitive to perturbations in RTK signalling. Reducing the Fgf8 gene dosage only partially rescued defects in the glossopharyngeal nerve and was not sufficient to rescue facial nerve defects, suggesting that FGF8 is functionally redundant with other RTK ligands during facial nerve development.

Variations in the course of the cervical vagus nerve on thyroid ultrasonography.

BACKGROUND AND PURPOSE: Only 1 ultrasonography study that described the variation of the VN had been published at the time our research was begun. The purpose of this study was to evaluate the incidence and type of variation in the course of the cervical VN on thyroid ultrasonography. MATERIALS AND METHODS: From August 2009 to September 2010, 163 consecutive patients were evaluated by sonography for the screening and characterization of thyroid nodules (mean age, 49.0 ± 14.4 years, male:female, 20:143). Two types of variation were defined as follows: 1) anterior variation, when the course of the VNs changed from the typical location to an anterior location in front of the CCA; and 2) medial variation, when the course of the VNs changed from the typical location to a location medial to the CCA (between CCA and thyroid gland). The incidence of the each variation was studied. RESULTS: Variation in the course of the VN occurred in 5.5% (18/326) of cases. The anterior variation was observed in 4.3% (14/326, right:left = 4:10), and the medial variation was observed in 1.2% (4/326, right:left = 3:1). For both variations, the VN was close to or nearly abutted the thyroid gland after it changed course. CONCLUSIONS: Variation in the course of the cervical VN could be assessed by ultrasonography. Two variations were observed in 5.5% of cases. The anterior variation was more common than the medial variation.

Absence of the vagus nerve in the stomach of Tbx1-/- mutant mice.

BACKGROUND: Tbx1 is a member of the Tbox family of binding domain transcription factors. TBX1 maps within the region of chromosome 22q11 deleted in humans with DiGeorge syndrome (DGS), a common genetic disorder characterized by numerous physical manifestations including craniofacial and cardiac anomalies. Mice with homozygous null mutations in Tbx1 phenocopy this disorder and have defects including abnormal cranial ganglia formation and cardiac neural crest cell migration. These defects prompted us to investigate whether extrinsic vagus nerve or intrinsic enteric nervous system abnormalities are prevalent in the gastrointestinal tract of Tbx1 mutant mice. METHODS: We used in situ hybridization for Ret, and immunohistochemical staining for neurofilament, HuC/D and ßIII-tubulin to study cranial ganglia, vagus nerve, and enteric nervous system development in Tbx1 mutant and control mice. KEY RESULTS: In Tbx1(-/-) embryos, cranial ganglia of the glossopharyngeal (IXth) and vagus (Xth) nerves were malformed and abnormally fused. In the gastrointestinal tract, the vagus nerves adjacent to the esophagus were severely hypoplastic and they did not extend beyond the gastro-esophageal junction nor project branches within the stomach wall, as was observed in Tbx1(+/+) mice. CONCLUSIONS & INFERENCES: Although cranial ganglia morphology appeared normal in Tbx1(+/-) mice, these animals had a spectrum of stomach vagus innervation defects ranging from mild to severe. In all Tbx1 genotypes, the intrinsic enteric nervous system developed normally. The deficit in vagal innervation of the stomach in mice mutant for a gene implicated in DGS raises the possibility that similar defects may underlie a number of as yet unidentified/unreported congenital disorders affecting gastrointestinal function.

A "pilot light" of the right non-recurrent laryngeal nerve.

Total thyroidectomy was performed in a 53-year-old male, with Graves-Basedow's disease. At surgery, the vagus nerve was found to be located medially to the carotid artery associated with a non-recurrent laryngeal nerve arising directly from the cervical vagus: this association has never been described in the literature. These results indicate that a medial location of the vagus nerve may be considered as a "pilot light" of the non-recurrent laryngeal nerve.

Unusual origin of the ansa cervicalis observed during carotid endarterectomy.

The surgical approach of the carotid artery for carotid endarterectomy demands knowledge of normal anatomy and anatomic variation. During carotid endarterectomy, a rare anatomic variant of the origin of the upper root of the ansa cervicalis was found. Contrary to commonly found anatomy, no upper root of the ansa cervicalis originating from the hypoglossal nerve was found. Instead, what seemed to be the ansa cervicalis originated from the vagus nerve and passed over the carotid bifurcation, branching to the infrahyoid muscles. Transection of this ansa cervicalis, for the purpose of good exposure, had no functional or cosmetic consequences.

The myenteric plexus of the esophagus is abnormal in an experimental congenital diaphragmatic hernia model.

BACKGROUND/AIM: Infants surviving congenital diaphragmatic hernia (CDH) suffer from anatomical and functional esophageal abnormalities. Previous work in the nitrofen animal model of CDH demonstrated malformations in neural crest-derived structures, including the vagus and recurrent laryngeal nerves. The aim of the present study was to assess whether the esophageal myenteric plexus is abnormal in rats with CDH. METHODS: We used the nitrofen-induced CDH fetal rat model. Two sections of the proximal, medium and distal esophagus from both groups were processed for immunohistochemical staining with anti-neuron specific enolase and anti-S-100 antibodies; the number of stained areas was recorded for each group. Whole-mount preparations of the entire esophagus of Control and CDH animals were histochemically stained for acetylcholinesterase; the density and area of the ganglia and the number of cells/ganglia were determined. Comparisons between groups were made by standard statistical methods. RESULTS: The number of immunohistochemically stained areas in transversal sections were decreased in CDH animals for anti-enolase (11.5+/-6.06 vs. 1.93+/-1.49, control vs. CDH, p<0.001) and anti S-100 antibodies (8.57+/-4.1 vs. 4.06+/-2.82, p<0.001). In whole-mount preparations the number of ganglia per high power field (35.16+/-6.57 vs. 29.29+/-10.26, p<0.05), the number of cells per ganglia (11.85+/-3.52 vs. 2.28+/-4.61, p<0.0001) and the relative area of the ganglia (0.35+/-0.32 vs. 0.18+/-0.42%, p<0.001), were also significantly decreased in CDH animals compared with Controls. CONCLUSIONS: Esophageal intrinsic innervation is defective in rat fetuses with CDH. If patients with CDH bear the same anomalies, this may explain some of their esophageal motility disorders. Finally, these findings support the concept of neural crest involvement in the pathogenic pathways of CDH.

Anomalous intrathoracic left vagus and recurrent laryngeal nerve course.

An anomalous course of the vagus nerve is an extremely rare congenital anomaly. We report the case of a 59-year-old man who had left lung cancer. We performed a left upper lobectomy and mediastinal lymphadenectomy, paying attention to the pathway of the left vagus nerve, which had an anomalous course passing anteriorly to the left pulmonary trunk between the apical and anterior branches. The left recurrent laryngeal nerve hooked around the lower border of the apical branch of the left pulmonary artery.

Perturbation of hoxb5 signaling in vagal neural crests down-regulates ret leading to intestinal hypoganglionosis in mice.

BACKGROUND & AIMS: The enteric nervous system (ENS) controls intestinal peristalsis, and defective development of this system results in hypo/aganglionosis, as seen in Hirschsprung's disease. In the embryo, vagal neural crest cells (NCC) migrate and colonize the intestine rostrocaudally then differentiate into the ganglia of the ENS. Vagal NCC express the homeobox gene Hoxb5, a transcriptional activator, in human and mouse, so we used transgenic mice to investigate the function of Hoxb5 and the receptor tyrosine kinase gene Ret, which is affected in many patients with Hirschsprung's disease, in ENS development. METHODS: We perturbed the Hoxb5 pathway by expressing a chimeric protein enb5, in which the transcription activation domain of Hoxb5 was replaced with the repressor domain of the Drosophila engrailed protein (en), in vagal NCC. This enb5 transcriptional repressor competes with wild-type Hoxb5 for binding to target genes, exerting a dominant negative effect. RESULTS: We observed that 30.6% +/- 2.3% of NCC expressed enb5 and that these enb5-expressing NCC failed to migrate to the distal intestine. A 34%-37% reduction of ganglia (hypoganglionosis) and slow peristalsis and, occasionally, absence of ganglia and intestinal obstruction were observed in enb5-expressing mice. Ret expression was markedly reduced or absent in NCC and ganglia, and enb5 blocked Hoxb5 induction of Ret in neuroblastoma cells. CONCLUSIONS: Our data indicate that Ret is a downstream target of Hoxb5 whose perturbation causes Ret haploinsufficiency, impaired NCC migration, and hypo/aganglionosis, suggesting that Hoxb5 may contribute to the etiology of Hirschsprung's disease.

An unreported variation of the cervical vagus nerve: anatomical and histological observations.

Variations involving the cervical portion of the vagus nerve are seemingly very rare. We report an adult male found to harbour a right cervical vagus nerve that crossed anterior to the right common carotid artery to terminate in the lateral aspect of the thyroid gland. A very small continuation of this nerve was found to continue distally into the thorax. Histologically, this part of the vagus nerve did not contain ganglion or other cell bodies. There were no heterologous inclusions (thyroid, parathyroid, thymus, salivary gland or branchial cleft remnants) present. Although grossly there was a connection into the thyroid gland, this was not observed histologically. No signs of trauma were found to the ipsilateral neck region. We hypothesise that this variation is due to entanglement between the thyroid gland and cervical vagus nerve during development. This rare variation might be considered by the clinician who operates in the cervical region or interprets imaging of the neck. To our knowledge, a vagus nerve with the above described morphology has not been described.

[Diagnostic complexities and anatomical surprises in a case of thyroid surgery for papillary carcinoma]. / Complessità diagnostiche e sorprese anatomiche in un caso di chirurgia tiroidea per carcinoma papillare.

We present the case of a male patient who needed surgery for a large undefined submandibular schwannoma and a small contralateral thyroid carcinoma associated with cervical lymph nodes of a dubious nature. During the operative procedure all the pathological conditions were resolved, with some remarkable surprises. A non-functioning parathyroid adenoma was found and removed. A fairly unusual anatomical complication was also detected with regard to the right inferior laryngeal nerve, i.e. an anastomotic branch connecting the main trunk to the vagus nerve.

The survival of vagal and glossopharyngeal sensory neurons is dependent upon dystonin.

The vagal and glossopharyngeal sensory ganglia and their peripheral tissues were examined in wild type and dystonia musculorum mice to assess the effect of dystonin loss of function on chemoreceptive neurons. In the mutant mouse, the number of vagal and glossopharyngeal sensory neurons was severely decreased (70% reduction) when compared with wild type littermates. The mutation also reduced the size of the circumvallate papilla (45% reduction) and the number of taste buds (89% reduction). In addition, immunohistochemical analysis demonstrated that the dystonin mutation reduced the number of PGP 9.5-, calcitonin gene-related peptide-, P2X3 receptor- and tyrosine hydroxylase-containing neurons. Their peripheral endings also decreased in the taste bud and epithelium of circumvallate papillae. These data together suggest that the survival of vagal and glossopharyngeal sensory neurons is dependent upon dystonin.

The vagus and recurrent laryngeal nerves in experimental congenital diaphragmatic hernia.

BACKGROUND: The etiology of the anatomic and functional abnormalities of the esophagus in infants surviving congenital diaphragmatic hernia (CDH) remains unclear. We showed previously that fetal rats with CDH have malformations of neural crest-derived structures. The aim of this study was to examine the anatomy of the vagus and the recurrent laryngeal nerves, both of neural crest origin, in rats with CDH. METHODS: We used the nitrofen-induced CDH fetal rat model. Nine control fetuses from four dams and nine fetuses with CDH from seven dams were included in this study. Embryos were fixed in formalin and a thoracic block from the larynx to tracheal bifurcation was serially sectioned in the horizontal plane. One in every ten sections was stained with hematoxylin and eosin. The image was digitalized using biological software (TDR-3dbase). Vagus and recurrent laryngeal nerves, trachea, esophagus and the great vessels were examined. In order to obtain the three-dimensional reconstructions, 90-120 consecutive images were used. RESULTS: In comparison with controls there were striking abnormalities of the vagus and the recurrent laryngeal nerves in fetuses with CDH: (1) absence of the left (2/9) or right (2/9) vagus nerves; (2) absence of the left (3/9) or right (3/9) recurrent laryngeal nerves; (3) marked hypoplasia of the trunk of the vagus (2/9); (4) deviations of their normal course and change of normal anatomical relationships into the mediastinum (2/9); and (5) abnormal branching of the lower portion of the vagus (1/9). CONCLUSIONS: Rat fetuses with CDH have anomalies of the vagus and recurrent laryngeal nerves that support the concept of a neural crest involvement in the origin of this malformation. 3-D reconstructions allow a detailed analysis and provide a precise insight into the real anatomy. These observations may explain esophageal motility disorders in CDH.

[The right inferior laryngeal nerve with a non-recurrent course]. / Il nervo laringeo inferiore destro a decorso non ricorrente.

Two cases of a right non-recurrent laryngeal nerve were encountered during the performance of 992 thyroid operations. In its abnormal non-recurrent course the nerve passes transversely from under the carotid sheat hand takes a position which is at right-angles to the normal recurrent laryngeal nerve.

Monolateral hypoplasia of the motor vagal nuclei in a case of sudden infant death syndrome.

During the development of motor vagal nuclei (MVN), the neuroblasts of the myeloencephalic basal plate migrate in the dorsolateral direction to form the dorsal motor vagal nucleus (DMVN) and ventrolaterally to form the ventral motor vagal nucleus (VMVN). Those neuroblasts that remain close to the median sulcus will form the hypoglossal nucleus. In support of the congenital origin of the alteration of the MVN in sudden infant death syndrome (SIDS), we report the case of an 8-month-old female child who was found dead in her cot. The neuropathological assessment revealed that the medullary triangle of the 4th ventricle floor was asymmetric, owing to the presence of three prominences to the left side of the median sulcus. The medial prominence corresponded to the hypoglossal nucleus, which showed a marked increase in the number of large neurons; the intermediate prominence corresponded to the DMVN whose large neurons were reduced and were recognizable mainly at the level of the medial fringe; the lateral prominence corresponded to the solitary nucleus. The left solitary tract showed a reduction of the transverse diameter. Also, the left VMVN showed marked reduction in the number of neurons. Inflammatory and astrocytic reactions were absent. We suggest that in SIDS cases the hypocellularity of the MVN and the increased number of neurons of the hypoglossal nucleus are intimately related, indicating a congenital alteration due to incomplete migration of the vagal neuroblasts with abnormality of the autonomic cardio-respiratory control.

Branchiogenic motoneurons innervating facial, masticatory, and esophageal muscles show aberrant distribution in the reeler-phenotype mutant rat, Shaking Rat Kawasaki.

Shaking Rat Kawasaki (SRK) is an autosomal recessive mutant rat that is characterized by cerebellar ataxia. Although previous studies indicated many points of similarity between this mutant rat and the reeler mouse, nonlaminated structures such as the facial nucleus have not been studied in this mutant rat. Nissl-stained sections through the brainstem showed that the cytoarchitecture of the facial, motor trigeminal, and ambiguus nuclei was abnormal in SRK, especially in the lateral cell group of the facial nucleus and the compact formation of the ambiguus nucleus. To examine whether orofacial motoneurons are also malpositioned in the SRK rat, horseradish peroxidase (HRP) was injected into the facial, masticatory, and abdominal esophageal muscles of the SRK rats and normal controls to label facial, trigeminal, and ambiguus motoneurons, respectively. HRP-labeled facial, trigeminal, and ambiguus motoneurons of the SRK rat were distributed more widely than those of their normal counterparts, as in the case of the reeler mouse, with the one exception that labeled facial motoneurons innervating the nasolabial muscle were distributed more widely in the ventrolateral-to-dorsomedial direction in comparison with those of the reeler mutant. These data demonstrate that nonlaminated structures in the brainstem of the SRK rat are affected severely, as is the case in the reeler mutant mouse.

The vagus and recurrent laryngeal nerves in the rodent experimental model of esophageal atresia.

BACKGROUND: After surgical correction of their esophageal atresia and tracheoesophageal fistula (EA-TEF), many patients exhibit evidence of esophageal dysmotility. Controversy exists as to whether the esophageal motility disorders result from denervation caused by surgery or from an inherent abnormal innervation of the esophagus. METHODS: The present study used an Adriamycin-induced EA-TEF fetal rat model to trace the course and branching of both the vagus and recurrent laryngeal nerves. Abnormalities observed in EA-TEF rat fetuses include: (1) fewer branches from both recurrent laryngeal nerves; (2) deviation of the left vagus from its normal course below the aorta, passing behind the fistula to approach and join with the right vagus to form a single nerve trunk on the right side of the esophagus; (3) relatively few branches from the single vagal nerve trunk (composed of fibers of the left and the right vagus) on the surface of the lower esophagus. CONCLUSIONS: Fetuses affected by EA-TEF have inherent abnormalities in the course and branching pattern of the vagus nerves as they descend through the thorax, culminating in a deficient extrinsic nerve fiber plexus in the lower esophagus. These observations may account for the esophageal motility disorders seen in patients who have EA-TEF even before surgical intervention.

Disruption of semaphorin III/D gene causes severe abnormality in peripheral nerve projection.

The molecules of the collapsin/semaphorin gene family have been thought to play an essential role in axon guidance during development. Semaphorin III/D is a member of this family, has been shown to repel dorsal root ganglion (DRG) axons in vitro, and has been implicated in the patterning of sensory afferents in the spinal cord. Although semaphorin III/D mRNA is expressed in a wide variety of neural and nonneural tissues in vivo, the role played by semaphorin III/D in regions other than the spinal cord is not known. Here, we show that mice homozygous for a targeted mutation in semaphorin III/D show severe abnormality in peripheral nerve projection. This abnormality is seen in the trigeminal, facial, vagus, accessory, and glossopharyngeal nerves but not in the oculomotor nerve. These results suggest that semaphorin III/D functions as a selective repellent in vivo.