Autonomic Ganglia Research Articles

Optimization of an autaptic culture system for studying cholinergic synapses in sympathetic ganglia.

An autaptic synapse (or 'autapse') is a functional connection between a neuron and itself, commonly used in studying the molecular mechanisms underlying synaptic transmission and plasticity in central neurons. Most previous studies on autonomic synaptic functions have relied on spontaneous connections among neurons in mass cultures. However, growing evidence supports the utility of microcultures cultivating autaptic neurons for examining cholinergic transmission within sympathetic ganglia. Despite these advancements, standardized protocols for culturing autaptic sympathetic neurons have yet to be established. Drawing on historical literature, this study delineates optimal experimental conditions to efficiently and reliably produce cholinergic synapses in sympathetic neurons within a short time frame. Our research emphasizes five key factors: (i) the generation of uniformly sized microislands of growth permissive substrates; (ii) the addition of nerve growth factor, ciliary neurotrophic factor (CNTF), and serum to the culture medium; (iii) independence from specific serum and neuronal medium types; (iv) the reciprocal roles of CNTF and glial cells; and (v) the promotion of cholinergic synaptogenesis in SCG neurons through indirect glia co-cultures, rather than direct glial feeder layer cultures. In conclusion, glia-free monocultures of SCG neurons are relatively simple to prepare and yield robust and reliable synaptic currents. This makes them an effective model system for straightforwardly addressing fundamental questions about neurogenic mechanisms involved in cholinergic synaptic transmission in autonomic ganglia. Furthermore, autaptic culture experiments could eventually be implemented to investigate the roles of functional neuron-satellite glia units in regulating cholinergic functions under physiological and pathological conditions.

Molecular Study of Varicella zoster virus in Cerebrospinal Fluid from Stroke Patients of Thi-Qar province.

Varicella zoster virus (VZV) is a type of alpha-herpesvirus that specifically targets the nervous system. The initial infection, typically occurring during childhood, results in varicella (commonly known as chickenpox), after which the virus enters a dormant state in cranial nerve ganglia, dorsal root ganglia, and autonomic ganglia throughout the entire neuroaxis. Molecular and genetic studies of viruses are an important tool for virus development and identifying viral treatments to combat the diseases. The aim of the study was to determine the whole ORF4 sequence of the local VZV strains for phylogenetic analysis to determine the variability in the viral sequence. Ten samples of VZV DNA were subjected to the sequencing of the whole ORF4 region following identification using the PCR method. Sequences from five samples have been successfully analyzed. All clinical strains were discovered to possess a genome with a length of 124,884 base pairs. The sequences exhibited the occurrence of two distinct mutations, one being a transversion and the other a transition, with the latter resulting in an alteration of the amino acid. A phylogenetic tree was constructed using the maximum likelihood method based on the sequences of five nucleotide sequences from clinical samples and nine reference VZV strains. The tree displayed the evolutionary distances between these sequences. The analysis of the phylogenetic tree revealed the presence of five primary clades, with four of them originating from India (isolates S1, S2, S4, S5), while S3 exhibited similarity to a strain from the United Kingdom.

Research and progress on the mechanism of lower urinary tract neuromodulation: a literature review.

The storage and periodic voiding of urine in the lower urinary tract are regulated by a complex neural control system that includes the brain, spinal cord, and peripheral autonomic ganglia. Investigating the neuromodulation mechanisms of the lower urinary tract helps to deepen our understanding of urine storage and voiding processes, reveal the mechanisms underlying lower urinary tract dysfunction, and provide new strategies and insights for the treatment and management of related diseases. However, the current understanding of the neuromodulation mechanisms of the lower urinary tract is still limited, and further research methods are needed to elucidate its mechanisms and potential pathological mechanisms. This article provides an overview of the research progress in the functional study of the lower urinary tract system, as well as the key neural regulatory mechanisms during the micturition process. In addition, the commonly used research methods for studying the regulatory mechanisms of the lower urinary tract and the methods for evaluating lower urinary tract function in rodents are discussed. Finally, the latest advances and prospects of artificial intelligence in the research of neuromodulation mechanisms of the lower urinary tract are discussed. This includes the potential roles of machine learning in the diagnosis of lower urinary tract diseases and intelligent-assisted surgical systems, as well as the application of data mining and pattern recognition techniques in advancing lower urinary tract research. Our aim is to provide researchers with novel strategies and insights for the treatment and management of lower urinary tract dysfunction by conducting in-depth research and gaining a comprehensive understanding of the latest advancements in the neural regulation mechanisms of the lower urinary tract.

Reduced unilateral sweating caused by varicella zoster virus infection: a case report

BackgroundHerpes zoster is an infectious skin disease caused by the reactivation of the varicella zoster virus (VZV), which has been latent in the posterior root ganglia of the spinal cord or cranial ganglia for an extended period. Neurological complications caused by herpes zoster include aseptic meningitis, white matter disease, peripheral motor neuropathy, and Guillain-Barré syndrome. However, reduced unilateral sweating caused by the VZV is very rare.Case PresentationThis article reports the case of a 34-year-old woman who was admitted to our hospital with sore throat, dizziness, and reduced sweating on the left side of her body. Physical examination found herpes lesions on the left upper lip and left external ear canal (scabbed) and reduced sweating on the left side of the body. Head magnetic resonance imaging (MRI) with contrast showed no abnormalities. After a lumbar puncture, the patient was diagnosed with viral meningitis by VZV infection. The electromyographic skin sympathetic reflex indicated damage to the left sympathetic nerve.ConclusionsSecondary unilateral sweating reduction is a rare neurological complication of herpes zoster, caused by damage to the autonomic nervous system. Literature review and comprehensive examination indicated that the reduced unilateral sweating was due to the activation of latent herpes zoster virus in the autonomic ganglia which has damaged the autonomic nervous system. For patients who exhibit acute hemibody sweat reduction, doctors should consider the possibility of secondary autonomic nervous system damage caused by herpes zoster.

Histopathology of the Tongue in a Hamster Model of COVID-19.

With altered sense of taste being a common symptom of coronavirus disease 2019 (COVID-19), our objective was to investigate the presence and distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) within the tongue over the course of infection. Golden Syrian hamsters were inoculated intranasally with SARS-CoV-2 and tongues were collected at 2, 3, 5, 8, 17, 21, 35, and 42 days post-infection (dpi) for analysis. In order to test for gross changes in the tongue, the papillae of the tongue were counted. Paraffin-embedded thin sections of the tongues were labeled for the presence of SARS-CoV-2 antigen. There was no difference in fungiform or filiform papillae density throughout the course of infection. SARS-CoV-2 antigen was observed in the circumvallate papillae taste buds (3-35 dpi) and autonomic ganglia (5-35 dpi), as well as in the serous and mucous salivary glands of the posterior tongue (2-42 dpi). The presence and distribution of SARS-CoV-2 suggest that the virus could cause taste disturbance by infecting the circumvallate taste buds. This effect could be exacerbated by a diminished secretion of saliva caused by infection of the serous salivary glands and the autonomic ganglia which innervate them.

Label-Free Assessment of Neuronal Activity Using Raman Micro-Spectroscopy.

Given the pivotal role of neuronal populations in various biological processes, assessing their collective output is crucial for understanding the nervous system's complex functions. Building on our prior development of a spiral scanning mechanism for the rapid acquisition of Raman spectra from single cells and incorporating machine learning for label-free evaluation of cell states, we investigated whether the Paint Raman Express Spectroscopy System (PRESS) can assess neuronal activities. We tested this hypothesis by examining the chemical responses of glutamatergic neurons as individual neurons and autonomic neuron ganglia as neuronal populations derived from human-induced pluripotent stem cells. The PRESS successfully acquired Raman spectra from both individual neurons and ganglia within a few seconds, achieving a signal-to-noise ratio sufficient for detailed analysis. To evaluate the ligand responsiveness of the induced neurons and ganglia, the Raman spectra were subjected to principal component and partial least squares discriminant analyses. The PRESS detected neuronal activity in response to glutamate and nicotine, which were absent in the absence of calcium. Additionally, the PRESS induced dose-dependent neuronal activity changes. These findings underscore the capability of the PRESS to assess individual neuronal activity and elucidate neuronal population dynamics and pharmacological responses, heralding new opportunities for drug discovery and regenerative medicine advancement.

Impact of Ethanol Infusion to the Vein of Marshall in Atrial Fibrillation and Atrial Tachycardia.

The ligament of Marshall is an epicardial structure characterized by its composition of fat, fibrous tissue, blood vessels, muscle bundles, nerve fibers, and ganglia. Its intricate network forms muscular connections with the coronary sinus and left atrium, alongside adjacent autonomic nerves and ganglion cells. This complexity plays a pivotal role in initiating focal electrical activities and sustaining micro- and macro-reentrant circuits, thereby contributing to the onset of atrial fibrillation and atrial tachycardia. However, endocardial ablation in this area may encounter challenges due to anatomical variations and insulation by fibrofatty tissue. Combining ethanol infusion into the vein of Marshall with radiofrequency ablation presents a promising strategy for effectively and safely eliminating this arrhythmogenic structure and terminating associated tachycardias.

КАРДИОНЕЙРОАБЛАЦИЯ – ФИЗИОЛОГИЧЕСКИЕ ОСНОВЫ МЕТОДА, КЛИНИЧЕСКОЕ ПРИМЕНЕНИЕ ПРИ НАРУШЕНИЯХ РИТМА СЕРДЦА

Increased tone of the parasympathetic part of the autonomic nervous system, affecting the pacemaker cells, may cause sinus bradycardia, develop long pauses of heart rhythm, paroxysmal or permanent atrioventricular block followed by reflex syncope. The usual reflex syncope treatment is conservative and includes avoiding situations that trigger syncope (prolonged standing, sight of blood etc.), tilt-training, adequate drinking regime, wearing compression underwear, sleeping with the head of the bed elevated and in some cases stimulating neuro- and vegetotropic therapy. Some patients are refractory to conventional methods of treatment and retain severe symptoms that worsens quality of their life seriously. These patients may be required a pacemaker implantation subsequently. Cardioneuroablation is an alternative treatment in patients with overactive parasympathetic nervous system that is based on radiofrequency catheter ablation of the major parasympathetic autonomic ganglia around the heart.

Evaluation of heart rate variability at 1-month after pulsed field ablation of atrial fibrillation and comparison with radiofrequency ablation

Abstract Background Pulsed Field Ablation (PFA) of atrial fibrillation (AF) is a nonthermal novel ablative modality in which high-voltage electric pulses are delivered to generate a high myocardial tissue-specific cellular death, with negligible consequences on surrounding structures including ganglionated plexi. The impairment of the cardiac autonomic ganglia after AF ablation with radiofrequency (RF) has been associated with an increase in mean heart rate (HR) and a reduction in heart rate variability (HRV) and might influence the long-term success of AF ablation. Little data is available on the effect of PFA on cardiac autonomic nervous function. Purpose The aim of this study is to investigate whether PFA ablation could lead to different values of HR and HRV compared to RF at 1-month post-ablation 24-hour Holter monitoring. Methods Between January to September 2023, we included consecutive patients undergoing AF ablation with PFA. According to our clinical practice, all patients performed a routine 24-hour Holter monitoring at 1-month post-ablation. Consecutive AF patients treated with RF were used as controls. Patients in treatment with antiarrhythmics or with documented recurrences of AF at 1-month post-ablation Holter monitoring were excluded. Results 22 consecutive PFA patients were compared to 22 consecutive RF controls. There were no differences in demographic, clinical and echocardiographic data between the 2 groups (Table 1). At 1-month post-ablation Holter monitoring (Table 2), PFA patients had significant higher values of VarIndex (2.18±0.9 vs 1.47±0.7, p=0.01), ASDNN/5min (52.37±15.93 vs 37.17±12.96, p<0.01), SDANN/5min (116.50±27.97 vs 96.03±28.38, p=0.04), and SD (128.95±31.31 vs 106.30±29.56, p=0.04). There was no difference in minimum HR (47.00±6.59 vs 50.29±10.25, p=0.21), mean HR (67.77±6.63 vs 69.24±9.71, p=0.56), and maximal HR (115.41±18.12 vs 110.81±16.44, p=0.39). Conclusions PFA leads to higher values of HRV parameters (i.e., VarIndex, ASDNN/5min, SDANN/5min, and SD) at 1-month post-ablation compared to RF. These data suggest a higher preservation of cardiac autonomic function with PFA, in contrast to RF. Whether the preservation of cardiac autonomic function with PFA might lead to higher rate of long-term AF recurrences remains to be determined.Table 1Table 2

ST-2560, a selective inhibitor of the NaV1.7 sodium channel, affects nocifensive and cardiovascular reflexes in non-human primates.

The voltage-gated sodium channel isoform NaV1.7 is a high-interest target for the development of non-opioid analgesics due to its preferential expression in pain-sensing neurons. NaV1.7 is also expressed in autonomic neurons, yet its contribution to involuntary visceral reflexes has received limited attention. The small molecule inhibitor ST-2560 was advanced into pain behaviour and cardiovascular models to understand the pharmacodynamic effects of selective inhibition of NaV1.7. Potency of ST-2560 at NaV1.7 and off-target ion channels was evaluated by whole-cell patch-clamp electrophysiology. Effects on nocifensive reflexes were assessed in non-human primate (NHP) behavioural models, employing the chemical capsaicin and mechanical stimuli. Cardiovascular parameters were monitored continuously in freely-moving, telemetered NHPs following administration of vehicle and ST-2560. ST-2560 is a potent inhibitor (IC50 = 39 nM) of NaV1.7 in primates with ≥1000-fold selectivity over other isoforms of the human NaV1.x family. Following systemic administration, ST-2560 (0.1-0.3 mg·kg-1, s.c.) suppressed noxious mechanical- and chemical-evoked reflexes at free plasma concentrations threefold to fivefold above NaV1.7 IC50. ST-2560 (0.1-1.0 mg·kg-1, s.c.) also produced changes in haemodynamic parameters, most notably a 10- to 20-mmHg reduction in systolic and diastolic arterial blood pressure, at similar exposures. Acute pharmacological inhibition of NaV1.7 is antinociceptive, but also has the potential to impact the cardiovascular system. Further work is merited to understand the role of NaV1.7 in autonomic ganglia involved in the control of heart rate and blood pressure, and the effect of selective NaV1.7 inhibition on cardiovascular function.

Autoimmune Autonomic Ganglionopathy and Acute Autonomic Sensory Neuropathy

Autoimmune autonomic ganglionopathy (AAG) and acute autonomic sensory neuropathy (AASN) are immune-mediated neuropathies that affect the autonomic and/or dorsal root ganglia. Autoantibodies against the nicotinic ganglionic acetylcholine receptor (gAChR) detected in the sera of patients with AAG play a key role in the pathogenesis of this condition. Notably, gAChR antibodies are not detected in the sera of patients with AASN. Currently, AAG and AASN are not considered to be on the same spectrum with regard to disease concept based on clinical symptoms and laboratory findings. However, extra-autonomic brain symptoms (including psychiatric symptoms and personality changes) and endocrine disorders occur in both diseases, which suggests shared pathophysiology between the two conditions.

Factors Related to the Event Hypertension in Farmers

Pesticides are materials that are widely used in various sectors, improper and correct use of pesticides can cause health problems where pesticides can cause hypertension because pesticides that enter the human body will be able to increase the enzyme acetylcholinesterase or Ache, so that there will be an accumulation reaction in the joints. Clinogenic neuro-effectors and autonomic ganglion which have an impact on the emergence of hypertension problems. The method in this research uses a quantitative research design with a cross-sectional analytical approach, the sampling technique in this research uses a total sampling technique from all workers totaling 17 respondents who work as farmers, the data collected is primary data and a univariate analysis test is carried out and bivariate analysis with Chi-square test to find relationships. The results of this research found that 64.7% of respondents experienced hypertension and 35.3% did not experience hypertension. Based on the data analysis carried out, it was found that the incidence of hypertension was significantly higher in the age group ≥ 30, working period ≥ 8years, longwork ≥ 8O'clock,smoking status is yes and PPE equipment is not good with a p value <0.05.

A Review of the Mysterious Roles of the Autonomic Ganglia Considered as Deep Intelligence Agency in the United States of the Brain.

For centuries, the brain has been considered a single organ from an anatomical and functional perspective. However, while the cerebral cortex, consisting of many lobes and lobules, generally creates voluntary actions, autonomous parts of the brain also carry out vital activities such as survival, reproduction, and nutrition. The functions of the group of organs that carry out basic vital activities are modulated by autonomous ganglia that work like the deep intelligence networks of the brain. Information and energy packets produced as different molecules in vital organs and sent to the autonomous ganglia are decoded. These packages are then made available for use by cells, tissues, and organs. This deep information, purified and summarized by the autonomic ganglia, is presented to the cerebral cortex after passing through the control of the brainstem and insula. As a result, the entire brain and all the organs under its control decide together what to do. From this conceptual perspective, the brain is a united states group with diferent states under its management; the autonomic ganglia can also be thought of as the brain's deep intelligence networks.

Standing gustatory papillae biopsy procedure for antemortem diagnosis of equine grass sickness.

Diagnosing equine grass sickness (EGS) requires histopathological evidence of chromatolysis and/or neuronal loss in peripheral autonomic ganglia. Previous investigators performed postmortem biopsies of gustatory papillae located on the tongue and found chromatolytic subgemmal neurons in all 13 EGS horses. The present study aimed to design a standardized lingual biopsy sampling method through a transbuccal approach in healthy standing horses and assess the quality of the obtained samples, to allow antemortem diagnosis of EGS in clinical cases. 6 healthy horses. A transbuccal approach was performed bilaterally in 6 healthy standing horses. After having reached a deep level of sedation, horses were placed in stocks and a Günther mouth gag was inserted. Local anesthesia followed by a vertical full thickness incision was performed on both cheeks. Foliate papillae biopsies were carried out using an arthroscopic rongeur inserted through each incision site under oral endoscopic control. Tongue movements were restricted with diazepam. Histological assessment of taste buds and subgemmal plexi neurons was performed using H&E-stained longitudinal sections. The procedure was well tolerated in all horses. Minor complications observed were a transient facial paralysis, some incisional fluid collection, and abscesses. Ten samples (10/12) were suitable for assessment of neuronal perikarya. This procedure was safe for subgemmal plexus biopsy in healthy standing horses. The obtained samples were adequate as long as they were neatly cut lengthwise for inclusion. The technique was also used for 2 clinical cases and revealed the complete absence of neuronal perikarya, confirming chronic EGS.

Autoantibodies against gAChR in humans and mouse models of autoimmune autonomic ganglionopathy

AbstractThe ganglionic nicotinic acetylcholine receptor (gAChR) mediates fast synaptic transmission in all peripheral autonomic ganglia (sympathetic, parasympathetic, and enteric). Over the last two decades, evidence has accumulated for a role of autoantibodies against gAChR in the development of autoimmune autonomic ganglionopathy (AAG). In this review we provide an updated overview of the field, with a highlight on the role of autoimmunity against gAChR in the pathogenesis of AAG. Clinical data as well as findings from experimental disease models are summarized in sections focusing on the presence of autoantibodies against gAChR in patients with AAG, the function of gAChR antibodies, the association of antibodies against gAChR with AAG‐related phenotypes, the in vivo pathogenicity of transferred autoantibodies against gAChR in mice, and mouse models of the disease induced by immunization with the nicotinic AChR. Based on a comprehensive assessment of the currently available data, we propose a hypothetical model for the role of autoantibodies against gAChR in the pathogenesis of AAG.

Solitary Ganglioneuromatous Hamartoma Tongue in a Newborn - A Rare Entity.

Ganglioneuromatous hamartoma is a benign tumour of autonomic ganglia with very few cases reported in head and neck region. In this report, we are presenting a case of ganglioneuromatous hamartoma in a 20day old female child who presented with a tongue mass. She underwent a surgical excision and the definitive diagnosis was made by histopathology. This case reports discusses presentation and management of a case of ganglioneuromatous hamartoma.

Influence of terahertz waves on the binding of choline to choline acetyltransferase: insights from molecular dynamics simulations.

Acetylcholine (Ach) is a common neurotransmitter in the central nervous system (CNS) and peripheral nervous system (PNS). It is one of the neurotransmitters in the autonomic nervous system and the main neurotransmitter in all autonomic ganglia. Experiments have confirmed that electromagnetic waves can affect the synthesis of animal neurotransmitters, but the microscopic effects of electromagnetic waves in the terahertz (THz) frequency band are still unclear. Based on density functional theory (DFT) and molecular dynamics (MD) simulation methods, this paper studies the effect of THz electromagnetic waves on the binding of choline to choline acetyltransferase (ChAT). By emitting THz waves that resonate with the characteristic vibration mode of choline near the active site, it was found that THz waves with a frequency of 45.3 THz affected the binding of choline to ChAT, especially the binding of the active site histidine His324 to choline. The main evidence is that under the action of THz waves, the binding free energy of choline to histidine His324 and ChAT at the active site was significantly reduced compared to noE, which may have a potential impact on the enzymatic synthesis of Ach. It is expected to achieve the purpose of regulating the synthesis of the neurotransmitter Ach under the action of THz waves and treat certain nervous system diseases.

Store-operated calcium entry in the satellite glial cells of rat sympathetic ganglia.

Satellite glial cells (SGCs), a major type of glial cell in the autonomic ganglia, closely envelop the cell body and even the synaptic regions of a single neuron with a very narrow gap. This structurally unique organization suggests that autonomic neurons and SGCs may communicate reciprocally. Glial Ca2+ signaling is critical for controlling neural activity. Here, for the first time we identified the machinery of store-operated Ca2+ entry (SOCE) which is critical for cellular Ca2+ homeostasis in rat sympathetic ganglia under normal and pathological states. Quantitative realtime PCR and immunostaining analyses showed that Orai1 and stromal interaction molecules 1 (STIM1) proteins are the primary components of SOCE machinery in the sympathetic ganglia. When the internal Ca2+ stores were depleted in the absence of extracellular Ca2+, the number of plasmalemmal Orai1 puncta was increased in neurons and SGCs, suggesting activation of the Ca2+ entry channels. Intracellular Ca2+ imaging revealed that SOCE was present in SGCs and neurons; however, the magnitude of SOCE was much larger in the SGCs than in the neurons. The SOCE was significantly suppressed by GSK7975A, a selective Orai1 blocker, and Pyr6, a SOCE blocker. Lipopolysaccharide (LPS) upregulated the glial fibrillary acidic protein and Toll-like receptor 4 in the sympathetic ganglia. Importantly, LPS attenuated SOCE via downregulating Orai1 and STIM1 expression. In conclusion, sympathetic SGCs functionally express the SOCE machinery, which is indispensable for intracellular Ca2+ signaling. The SOCE is highly susceptible to inflammation, which may affect sympathetic neuronal activity and thereby autonomic output.

Chronic thromboembolic pulmonary hypertension: epidemiology, diagnosis, treatment — current state of the problem

Chronic thromboembolic pulmonary hypertension is group IV of pulmonary hypertension, which develops with occlusive-stenotic lesions of the pulmonary artery after a pulmonary embolism. There are no clear data on the epidemiology of this disease. At the same time, it is obvious that it is much more widespread than is commonly believed. This is due to the nonspecific clinical picture and the lack of awareness of clinicians about this disease. On the one hand, the pathogenesis of CTEPH is well studied and in many respects similar to pulmonary arterial hypertension, on the other hand, it is not clear why blood clots do not dissolve in a certain percentage of patients. Diagnosis of chronic thromboembolic pulmonary hypertension is fairly well described and should be carried out according to a special algorithm. The treatment of choice is pulmonary endarterectomy. In inoperable patients and patients with residual pulmonary hypertension after surgery, it is possible to perform balloon angioplasty of the pulmonary artery and PAH-specific therapy. In our study, the safety and efficacy of a new method for the treatment of a residual form of chronic thromboembolic pulmonary hypertension, radiofrequency denervation of the pulmonary artery, has been proven. The pathogenetic basis of this technique is the desympathization of the pulmonary circulation by radiofrequency destruction of the autonomic ganglia of the bifurcation of the pulmonary artery and the interruption of the so-called pulmo-pulmonary reflex.

SAT547 Hereditary Paraganglioma: The Rare Co-Existence Of Two Genetic Syndromes Associated With PPGL-pheochromocytoma

Abstract Disclosure: K. Samuel: None. Hereditary Paraganglioma: the rare co-existence of two genetic syndromes associated with PPGL-Pheochromocytoma Kelara Samuel MD, Bryan McIver MD, Colleen Veloski MD, Julie Hallanger-Johnson MD, Valentina D. Tarasova, John Tourtelot MD, George Q. Yang MD, Sarimar Agosto-Salgado MD Background: Paragangliomas are neuroendocrine tumors arising from neural crest chromaffin cells of the autonomic ganglia and can be parasympathetic or sympathetic in nature. Approximately 30 percent of all paragangliomas are hereditary either associated with familial paraganglioma syndromes and other autosomal dominant syndromes, such as multiple neuroendocrine neoplasia 2A and 2B, neurofibromatosis type 1, and von Hippel Lindau disease.Case: A 73-year-old Hispanic female with a past medical history of hypothyroidism, hypertension, hyperlipidemia, and Lupus presented with a large neck mass of 11 years of evolution. An evaluation revealed a large near 12cm hypervascular, hyperenhancing left neck mass that encased the distal common carotid artery, carotid bifurcation, and internal and external carotid arteries and their branches. The multidisciplinary team recommended, given the tumor's extent, a non-surgical localized treatment consisting of radiation. Clinically, the patient had compressive symptoms, including tenderness over the tumor region, hoarseness, dysphagia, and changes in phonation. The patient also had a positive family history of paraganglioma in her grandson and nephew, but specific genetic alteration data from relatives was unavailable. Plasma normetanephrines were 0.68 (normal range 0-0.89), and plasma metanephrines were 0.23 (normal range 0-0.49). Genetic testing was positive for germline alterations in both SDHB p.Q214 and NF1 c.2970_2972delAAT. At this time, there is no evidence of metastatic disease and no clinical manifestations of NF1, suggesting a mild neurofibromatosis phenotype. Restaging imaging revealed an ongoing partial response to radiation and clinically patient has noted a significant improvement in the prior compressive symptoms. Conclusion: We present a case where we see an uncommon presentation of a non-secretory, hereditary paraganglioma with two concomitant rare genetic syndromes. This case highlights the importance of genetic testing for patient-appropriate tumor surveillance and family counseling implications. Presentation Date: Saturday, June 17, 2023