Genetic changes in the FH gene cause vagal paraganglioma.

Vagal paraganglioma (VPGL) is a rare neuroendocrine tumor that originates from the paraganglion associated with the vagus nerve. VPGLs present challenges in terms of diagnostics and treatment. VPGL can occur as a hereditary tumor and, like other head and neck paragangliomas, is most frequently associated with mutations in the SDHx genes. However, data regarding the genetics of VPGL are limited. Herein, we report a rare case of a 41-year-old woman with VPGL carrying a germline variant in the FH gene. Using whole-exome sequencing, a variant, FH p.S249R, was identified; no variants were found in other PPGL susceptibility and candidate genes. Loss of heterozygosity analysis revealed the loss of the wild-type allele of the FH gene in the tumor. The pathogenic effect of the p.S249R variant on FH activity was confirmed by immunohistochemistry for S-(2-succino)cysteine (2SC). Potentially deleterious somatic variants were found in three genes, SLC7A7, ZNF225, and MED23. The latter two encode transcriptional regulators that can impact gene expression deregulation and are involved in tumor development and progression. Moreover, FH-mutated VPGL was characterized by a molecular phenotype different from SDHx-mutated PPGLs. In conclusion, the association of genetic changes in the FH gene with the development of VPGL was demonstrated. The germline variant FH: p.S249R and somatic deletion of the second allele can lead to biallelic gene damage that promotes tumor initiation. These results expand the clinical and mutation spectra of FH-related disorders and improve our understanding of the molecular genetic mechanisms underlying the pathogenesis of VPGL.

Functional vagal paraganglioma developing 15 years after resection of a retroperitoneal paraganglioma.

The patient, a 40-year-old woman, was diagnosed as having a functional right vagal paraganglioma (PGL) 15 years after undergoing resection for a retroperitoneal PGL. 123I-MIBG scintigraphy showed no accumulation, but as the blood noradrenaline and urinary normetanephrine concentrations were elevated, the tumor was judged as being functional, and surgery was scheduled. The patient was started on doxazosin infusion and embolization of the tumor feeding vessel was performed before the surgery. Intraoperative examination showed that the tumor was contiguous with the vagal nerve, necessitating combined resection of the vagal nerve with the tumor. Postoperatively, the catecholamine levels returned to normal range. Histopathologically, the tumor was diagnosed as a moderately differentiated, intermediate-malignant-grade PGL, with a GAPP score of 4 to 6. No non-chromaffin tissue was observed in the tumor background, so that the functional vagal PGL was considered as a sporadic metachronous tumor rather than as a metastasis from the retroperitoneal PGL. More than half of head and neck paragangliomas (HNPGLs) are reported to arise in the carotid body, and about 5% from the vagal nerve. In addition, HNPGLs rarely produce catecholamines. Herein, we consider the relationship with the previously resected retroperitoneal PGL based on a review of the literature.

Computed tomographic features of canine intracranial and jugular foraminal masses involving the combined glossopharyngeal, vagus, and accessory nerve roots.

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.

Report of a vagal paraganglioma at the cervicothoracic junction.

BACKGROUND: Vagus nerve paragangliomas are rare tumors, comprising 0.03% of head and neck neoplasms. These tumors are usually located cephalad to the hyoid bone, and there is only one previously reported case that arose from the lower third of the neck. METHODS: We describe the second reported case of a lower neck vagus nerve paraganglioma that was managed with a limited sternotomy for access and surgical removal. RESULTS: A 66-year-old male presented with a long-standing lesion of the cervicothoracic junction. CT, MRI, and Ga-68 DOTATATE PET/CT showed an avidly enhancing 5.2 × 4.2 × 11.5 cm mass extending from C6 to approximately T4 level. FNA confirmed the diagnosis. The patient underwent catheter angiography and embolization via direct puncture technique followed by excision of the mass via a combined transcervical and limited sternotomy approach. CONCLUSION: We describe an unusual case of vagal paraganglioma at the cervicothoracic junction with retrosternal extension requiring a sternotomy for surgical excision.

Cervical vagal nerve schwannoma induced arrhythmia: a rare case report and literature review.

BACKGROUND: Schwannomas are benign tumors deriving from the sheath of cranial and peripheral nerves. The vagus nerve is comprised of a complex neuro-endocrine-immune network that maintains homeostasis, most tracts of it play a role in parasympathetic activity. We present an example of a rare cervical vagal schwannoma case accompanied by arrhythmia. CASE PRESENTATION: A 35-year-old female patient with a left cervical vagus schwannoma and ventricular arrhythmia underwent schwannoma resection in the operating room. The patient's suppressed heart rate increased after tumor removal, and the cardiac rhythm returned to normal postoperatively. Pathological examination demonstrated the diagnosis of schwannoma. CONCLUSIONS: This case explains the link between the vagus nerve and the cardiovascular system, proving that a damaged cervical vagus nerve can inhibit the heart rate and lead to arrhythmias, and eventually requiring surgical intervention.

[A case report of giant vagal schwannoma in the right neck and literature review].

Vagal nerve-derived schwannomas are rare, especially those with huge tumors. This paper reports a case of giant tumor in the right neck. The patient was misdiagnosed as pleomorphic adenoma before operation, and was diagnosed as schwannoma during operation. The clinical manifestations, diagnosis, differential diagnosis, treatment and prognosis are discussed in this paper based on the history and related literature.

[Vagal Schwannoma in the Middle Mediastinum Found by Atelectasis on Chest X-ray:Report of a Case].

An 70-year-old woman was reffered to our hospital to examine for a left lower lobe atelectasis on chest X-ray. Chest computed tomography (CT) showed the mass in middle mediastinum. The video-assisted thoracoscopic surgery( VATS) was performed to establish diagnosis and treat. 50 mm mass was found in the area surrounded by the descending thorasic aorta, esophagus, left atrium, left lower lobe, and mesiastinal pleura, and was regarded as a neurogenic tumor originating from the pulmonary branch of the vagal nerve. The histopathological diagnosis was benign schwannoma. She was dischraged on the seventh postoperative day, without any neurological complications.

Technique Nuances for Functional Preservation of Lower Cranial Nerves during Surgical Management of Ventral Foramen Magnum Meningiomas Via a Dorsal Lateral Approach.

BACKGROUND: This study established novel technique nuances in surgery for ventral foramen magnum meningiomas (vFMMs) via a dorsal lateral approach. METHODS: From July 2012 to July 2019, 37 patients with vFMMs underwent tumor resection surgery and were operated on with a dorsal lateral approach. Two safe zones were selected as the entrance of the surgical corridor. Safe zone I was located between the dural attachment of the first dental ligament (FDL) and the branches of C1; safe zone II lay between the dural attachment of the FDL and the jugular foramen. The tumor was debulked first through safe zone I and then through safe zone II. The tumor was removed through a trajectory from the caudal to cephalad to allow tumor debulking from below and downward delivery, away from the brainstem and lower cranial nerves. RESULTS: Thirty-three patients underwent gross total resection, and 4 patients underwent subtotal resection. Four patients transiently required a nasogastric feeding tube. All patients recovered within 3 months postoperatively. Three patients (8.1%) developed permanent mild hoarseness and dysphagia as a result of postoperative damage of cranial nerves IX and X. One patient underwent tracheotomy. No patient experienced tumor recurrence during the follow-up period. CONCLUSIONS: We established a minimal retraction principle, in which the selection of 2 safe zones as the entrance of the surgical corridor, tumor removal from the inferior to superior direction, and debulking followed by devascularization were the key elements to implement the minimal retraction principle in vFMM surgery.

Multiple paragangliomas: a case report.

BACKGROUND: Carotid and vagal paragangliomas (CPGLs and VPGLs) are rare neoplasms that arise from the paraganglia located at the bifurcation of carotid arteries and vagal trunk, respectively. Both tumors can occur jointly as multiple paragangliomas accounting for approximately 10 to 20% of all head and neck paragangliomas. However, molecular and genetic mechanisms underlying the pathogenesis of multiple paragangliomas remain elusive. CASE PRESENTATION: We report a case of multiple paragangliomas in a patient, manifesting as bilateral CPGL and unilateral VPGL. Tumors were revealed via computed tomography and ultrasound study and were resected in two subsequent surgeries. Both CPGLs and VPGL were subjected to immunostaining for succinate dehydrogenase (SDH) subunits and exome analysis. A likely pathogenic germline variant in the SDHD gene was indicated, while likely pathogenic somatic variants differed among the tumors. CONCLUSIONS: The identified germline variant in the SDHD gene seems to be a driver in the development of multiple paragangliomas. However, different spectra of somatic variants identified in each tumor indicate individual molecular mechanisms underlying their pathogenesis.

Mutation profiling in eight cases of vagal paragangliomas.

BACKGROUND: Vagal paragangliomas (VPGLs) belong to a group of rare head and neck neuroendocrine tumors. VPGLs arise from the vagus nerve and are less common than carotid paragangliomas. Both diagnostics and therapy of the tumors raise significant challenges. Besides, the genetic and molecular mechanisms behind VPGL pathogenesis are poorly understood. METHODS: The collection of VPGLs obtained from 8 patients of Russian population was used in the study. Exome library preparation and high-throughput sequencing of VPGLs were performed using an Illumina technology. RESULTS: Based on exome analysis, we identified pathogenic/likely pathogenic variants of the SDHx genes, frequently mutated in paragangliomas/pheochromocytomas. SDHB variants were found in three patients, whereas SDHD was mutated in two cases. Moreover, likely pathogenic missense variants were also detected in SDHAF3 and SDHAF4 genes encoding for assembly factors for the succinate dehydrogenase (SDH) complex. In a patient, we found a novel variant of the IDH2 gene that was predicted as pathogenic by a series of algorithms used (such as SIFT, PolyPhen2, FATHMM, MutationTaster, and LRT). Additionally, pathogenic/likely pathogenic variants were determined for several genes, including novel genes and some genes previously reported as associated with different types of tumors. CONCLUSIONS: Results indicate a high heterogeneity among VPGLs, however, it seems that driver events in most cases are associated with mutations in the SDHx genes and SDH assembly factor-coding genes that lead to disruptions in the SDH complex.

Cranial Nerve IX and X Weakness: An Unusual Initial Presentation of Myasthenia Gravis.

BACKGROUND Myasthenia gravis (MG) is an autoimmune disease characterized by antibodies binding skeletal muscle acetylcholine receptors (AChR). Rarely does the disease manifest with orolaryngeal symptoms before ocular ones. We present a case of MG that on initial presentation had symptoms of cranial nerves (CN) IX and X weakness, including dysphagia and dysphonia. CASE REPORT A 51-year-old woman with panic attacks presented to the Emergency Department (ED) with complaints of her throat closing, swallowing difficulty, and hoarse voice. Multiple ED visits revealed no etiology. However, she developed stridor, which prompted further evaluation. Laryngoscopy and imaging studies revealed no gross abnormalities; therefore, her symptoms of dysphonia and difficulty breathing were attributed to anxiety. Her hospital course was complicated by a cardiac arrest requiring intubation. ECHO, CTA chest, and MRI brain were unremarkable. Her cardiac arrest was hypothesized as being secondary to laryngeal spasm. During her ICU course, she failed extubation multiple times due to acute respiratory failure. An autoimmune etiology was suspected, prompting a paraneoplastic screen, which revealed elevated levels of AChR antibodies at 124 mmol/L. MG was diagnosed and treatment with plasmapheresis and steroids was initiated. However, complications of thrombocytopenia, anemia, and ARDS ensued, so MG treatment was discontinued. The patient was eventually transferred to a LTACH. Thereafter, at outpatient followup, her MG was treated with mycophenolate and prednisone, which led to significant symptom improvement. CONCLUSIONS MG commonly presents in the third decade with clinical features of ptosis, diplopia, and facial weakness. However, initial and isolated symptoms of dysphagia and dysphonia are rare, leading to missed diagnoses. Our case of a middle-aged woman posed a diagnostic challenge because of her uncommon presentation and comorbidities of panic attacks and obesity. This case highlights the crucial need for a high index of clinical suspicion for MG in any patient presenting with symptoms of CN IX and X weakness.

Left Paraglossal Approach for Airway Management of Patient With Large Neck Mass in an Austere Environment: A Case Report.

We present the case of a 25-year-old man with a significant neck mass and describe the technique used for managing his airway given limited equipment in an austere environment. Physical examination and imaging revealed significant proximal airway involvement. Without access to a fiberoptic bronchoscope, we sought a technique that might avoid contact with the mass from both the laryngoscope and endotracheal tube. In this case report, we describe our approach to left paraglossal laryngoscopy and intubation under general anesthesia-a method not well described in the literature and proved to be imperative for our airway management.

Utility of the plasma pancreatic polypeptide response to modified sham feeding in diabetic gastroenteropathy and non-ulcer dyspepsia.

BACKGROUND: The relationship between cardiovascular and gastrointestinal (ie, plasma pancreatic polypeptide [PP] response to modified sham feeding [MSF]) indices of vagal function is unclear. Hyperglycemia inhibits PP secretion via vagally mediated mechanisms. Our aims were to (a) compare the PP response, (b) its relationship with glycemia, and (c) the relationship between PP response to MSF, gastric emptying (GE) of solids, and symptoms during GE study in healthy controls, patients with diabetic gastroenteropathy (DM), and non-ulcer dyspepsia (NUD). METHODS: In 24 healthy controls, 40 DM, and 40 NUD patients, we measured plasma PP concentrations during MSF, cardiovagal functions, GE, and symptoms during a GE study. KEY RESULTS: Baseline PP concentrations were higher in DM than in controls and NUD (P = .01), and in type 2 than in type 1 DM patients (P < .01). The PP increment during MSF was normal (≥20 pg/mL) in 70% of controls, 54% of DM, and 47% of NUD patients. Overall, the PP response and cardiovagal tests were concordant (P = .01). Among patients with a reduced PP increment with MSF, 7/10 of T1DM and 1/7 of T2DM patients had moderate or severe cardiovagal dysfunctions (P < .05). The PP response to MSF was not associated with GE. CONCLUSIONS & INFERENCES: Up to 30% of healthy controls have a reduced PP increment during MSF, limiting the utility of this test to detect vagal injury. The PP response is more useful when it is normal than abnormal. A reduced PP response is more likely to be associated with cardiovagal dysfunctions in T1DM than in T2DM.

Vocal cord paralysis due to ectopic parathyroid adenoma and function recovery: a case report and review of the literature.

Ectopic parathyroid adenomas (PAs) can occur in numerous locations and are thought to be the cause of a significant portion of failed primary surgery for hyperparathyroidism. PA is a rare cause of hoarseness, which may be harbingers of a malignant process. Here, we describe an unusual case of an ectopic PA in the carotid sheath presenting as unilateral vocal cord paralysis (VCP). A 49-year-old lady presented with a 1-week history of hoarseness, irritating cough and shortness of breath. Fibreoptic laryngoscopy revealed left VCP. Ultrasound and computed tomography of the neck demonstrated a mass in the carotid sheath. Laboratory investigations revealed hypercalcemia (3.10 mmol/L), hypophosphatemia (0.81 mmol/L) and elevated intact parathyroid hormone (iPTH) level (381.6 pg/mL), despite of a negative 99mTc-sestamibi scan. After more rigorous tests, the ectopic tumor adjacent to the left vagus nerve was successfully resected, with subsequent histopathological confirmation of PA. The patient eventually got a normal iPTH level and serum calcium postoperatively, and regular voice function was also regained 4 months after surgery. This case emphasizes the importance of broad differential diagnosis and thorough workup. Although most patients with PA present with hypercalcemia, this disease entity also need to be considered in the differentials of neck masses and VCP.

Magnetic Resonance Imaging Features of Collet-Sicard Syndrome Associated With Glomus Jugulare Paraganglioma.

Collet-Sicard syndrome is an unusual disorder. The authors here demonstrated the Magnetic resonance (MR) imaging findings of the Collet-Sicard syndrome associated with glomus jugulare tumor. Neoplastic or non-neoplastic lesion of skull base can cause Collet-Sicard syndrome. MR imaging can be used successfully to demonstrate the etiology of this syndrome.

Intraoperative mapping and monitoring of sensory vagal fibers during vagal schwannoma resection.

Vagal schwannomas are rare, benign tumors. Intermittent intraoperative neuromonitoring via selective stimulation of splayed motor fibers running on the schwannoma surface to elicit a compound muscle action potential has been previously reported as a method of preserving vagal motor fibers. In this case report, vagal sensory fibers are mapped and continuously monitored intraoperatively during high vagus schwannoma resection using the laryngeal adductor reflex (LAR). Mapping of nerve fibers on the schwannoma surface enabled identification of sensory fibers. Continuous LAR monitoring during schwannoma subcapsular microsurgical dissection enabled sensory (and motor) vagal fibers to be monitored in real time with excellent postoperative functional outcomes. Laryngoscope, 129:E434-E436, 2019.