Autonomic Ganglia Research Articles

RBD in pure autonomic failure

Pure autonomic failure is considered to be a degenerative condition of the autonomic nervous resulting from accumulation of alpha-synuclein in autonomic ganglia [1,2]. Lack of CNS involvement distinguishes this disorder from other synucleopathies with CNS involvement like MSA, DLB and PD. However, long term follow-up of PAF patients has shown that some of these cases convert to one of these disorders most commonly MSA [3]. Also, recent data, albeit limited in nature has shown the association of REM sleep disorder in PAF patients challenging the previous notion that PAF is a disease restricted to autonomic nervous system. This data has led to the discovery of a clinical syndrome with a position in the middle of the spectrum of these disorders with PAF at one end of the spectrum and MSA, DLB and PD at the other end. We hereby present a case report of one such patient with PAF associated with RBD but without any other CNS manifestations.

Clinical analysis of cardiac autonomic ganglion plexus ablation for bradyarrhythmia: Research protocol for an intervention study.

This study aimed to explore the safety and effectiveness of selective cardiac autonomic ganglion plexus (GP) ablation on patients with bradyarrhythmia. The heart is controlled by its own intrinsic and central autonomic nerves. Increased cardiac vagal tone leads to sinus node dysfunction and atrioventricular conduction disorders, resulting in bradyarrhythmia. Pacemaker implantation can relieve the symptoms of arrhythmia caused by bradycardia, but it is not easy for patients to accept a pacemaker implantation as a form of treatment. Therefore, more and more attention has been paid to cardiac vagus nerve ablation. In this study, 20 patients who met the inclusion criteria of GP ablation in the First Affiliated Hospital of Xinjiang Medical University from November 2019 to June 2020 were enrolled. Biochemical and other related examinations along with electrophysiological examinations were conducted before ablation, and then cardiac GP ablation was performed. The patients were followed up 3 times at 3, 6, and 12 months after the operation. The minimum HR and mean HR were significantly increased after treatment with cardiac autonomic GP ablation (p<0.01). Moreover, the SDNN (Standard deviation of Normal-to-Normal Intervals) and RMSSD (Root mean square successive differences between successive R-R intervals) was significantly decreased after treatment with cardiac autonomic ganglion plexus ablation for 6 months and 12 months (p<0.01). Cardiac GP ablation is relatively simple and easy to implement in units that have performed radiofrequency ablation for bradyarrhythmias. This procedure can be performed without any new equipment. Some patients with bradycardia may not have a permanent pacemaker implantation and may go in for additional treatment options.

Ageing promotes pathological alpha-synuclein propagation and autonomic dysfunction in wild-type rats.

Neuronal aggregates of misfolded alpha-synuclein protein are found in the brain and periphery of patients with Parkinson’s disease. Braak and colleagues have hypothesized that the initial formation of misfolded alpha-synuclein may start in the gut, and then spread to the brain via peripheral autonomic nerves hereby affecting several organs, including the heart and intestine. Age is considered the greatest risk factor for Parkinson’s disease, but the effect of age on the formation of pathology and its propagation has not been studied in detail. We aimed to investigate whether propagation of alpha-synuclein pathology from the gut to the brain is more efficient in old versus young wild-type rats, upon gastrointestinal injection of aggregated alpha-synuclein. Our results demonstrate a robust age-dependent gut-to-brain and brain-to-gut spread of alpha-synuclein pathology along the sympathetic and parasympathetic nerves, resulting in age-dependent dysfunction of the heart and stomach, as observed in patients with Parkinson’s disease. Moreover, alpha-synuclein pathology is more densely packed and resistant to enzymatic digestion in old rats, indicating an age-dependent maturation of alpha-synuclein aggregates. Our study is the first to provide a detailed investigation of alpha-synuclein pathology in several organs within one animal model, including the brain, skin, heart, intestine, spinal cord and autonomic ganglia. Taken together, our findings suggest that age is a crucial factor for alpha-synuclein aggregation and complete propagation to heart, stomach and skin, similar to patients. Given that age is the greatest risk factor for human Parkinson’s disease, it seems likely that older experimental animals will yield the most relevant and reliable findings. These results have important implications for future research to optimize diagnostics and therapeutics in Parkinson’s disease and other age-associated synucleinopathies. Increased emphasis should be placed on using aged animals in preclinical studies and to elucidate the nature of age-dependent interactions.

Changes in Heart Rate and Heart Rate Variability During Surgical Stages to Completed Fontan Circulation

Arrhythmia is related to heart rate variability (HRV), which reflects the autonomic nervous regulation of the heart. We hypothesized that autonomic nervous ganglia, located at the junction of the superior vena cava’s entrance to the heart, may be affected during the bidirectional Glenn procedure (BDG), resulting in reduced HRV. We aimed to investigate changes in heart rate and HRV in a cohort of children with univentricular heart defects, undergoing stepwise surgery towards total cavopulmonary connection (TCPC), and compare these results with healthy controls. Twenty four hours Holter-ECG recordings were obtained before BDG (n = 47), after BDG (n = 47), and after total cavopulmonary connection (TCPC) (n = 45) in patients and in 38 healthy controls. HRV was analyzed by spectral and Poincaré methods. Age-related z scores were calculated and compared using linear mixed effects modeling. Total HRV was significantly lower in patients before BDG when compared to healthy controls. The mean heart rate was significantly reduced in patients after BDG compared to before BDG. Compared to healthy controls, patients operated with BDG had significantly reduced heart rate and reduced total HRV. Patients with TCPC showed reduced heart rate and HRV compared with healthy controls. In patients after TCPC, total HRV was decreased compared to before TCPC. Heart rate was reduced after BDG procedure, and further reductions of HRV were seen post-TCPC. Our results indicate that autonomic regulation of cardiac rhythm is affected both after BDG and again after TCPC. This may be reflected as, and contribute to, postoperative arrhythmic events.

Spatiotemporal mapping of sensory and motor innervation of the embryonic and postnatal mouse urinary bladder

The primary function of the urinary bladder is to store urine (continence) until a suitable time for voiding (micturition). These distinct processes are determined by the coordinated activation of sensory and motor components of the nervous system, which matures to enable voluntary control at the time of weaning. Our aim was to define the development and maturation of the nerve-organ interface of the mouse urinary bladder by mapping the organ and tissue distribution of major classes of autonomic (motor) and sensory axons. Innervation of the bladder was evident from E13 and progressed dorsoventrally. Increasing defasciculation of axon bundles to single axons within the muscle occurred through the prenatal period, and in several classes of axons underwent further maturation until P7. Urothelial innervation occurred more slowly than muscle innervation and showed a clear regional difference, from E18 the bladder neck having the highest density of urothelial nerves. These features of innervation were similar in males and females but varied in timing and tissue density between different axon classes. We also analysed the pelvic ganglion, the major source of motor axons that innervate the lower urinary tract and other pelvic organs. Cholinergic, nitrergic (subset of cholinergic) and noradrenergic neuronal cell bodies were present prior to visualization of these axon classes within the bladder. Examination of cholinergic structures within the pelvic ganglion indicated that connections from spinal preganglionic neurons to pelvic ganglion neurons were already present by E12, a time at which these autonomic ganglion neurons had not yet innervated the bladder. These putative preganglionic inputs increased in density prior to birth as axon terminal fields continued to expand within the bladder tissues. Our studies also revealed in numerous pelvic ganglion neurons an unexpected transient expression of calcitonin gene-related peptide, a peptide commonly used to visualise the peptidergic class of visceral sensory axons. Together, our outcomes enhance our understanding of neural regulatory elements in the lower urinary tract during development and provide a foundation for studies of plasticity and regenerative capacity in the adult system.

High-specific-activity 131iodine-metaiodobenzylguanidine for therapy of unresectable pheochromocytoma and paraganglioma.

Pheochromocytomas and paragangliomas (PPG) are rare cancers arising from the adrenal medulla (pheochromocytoma) or autonomic ganglia (paraganglioma). They have highly variable biological behavior. Most PPG express high-affinity norepinephrine transporters, allowing active uptake of the norepinephrine analog, 131iodine-metaiodobenzylguanidine (131I-MIBG). Low-specific-activity forms of 131I-MIBG have been used since 1983 for therapy of PPG. High-specific-activity131I-MIBG therapy improves hypertension management, induces partial radiological response or stable disease, decreases biochemical markers of disease activityand is well tolerated by patients. This drug, approved in the USA in July 2018, is the first approved agent for patients with unresectable, locally advanced or metastatic PPG and imaging evidence of metaiodobenzylguanidine uptake, who require systemic anticancer therapy.

Metastatic Paraganglioma of the Spine With SDHB Mutation: Case Report and Review of the Literature.

Paragangliomas (PGLs) are rare neuroendocrine tumors that can arise from any autonomic ganglion of the body. Most PGLs do not metastasize. Here, we present a rare case of metastatic PGL of the spine in a patient with a germline pathogenic succinate dehydrogenase subunit B (SDHB) mutation. In addition to a case report we provide a literature review of metastatic spinal PGL to highlight the importance of genetic testing and long-term surveillance of these patients. A 45-year-old woman with history of spinal nerve root PGL, 17 years prior, presented with back pain of several months' duration. Imaging revealed multilevel lytic lesions throughout the cervical, thoracic, and lumbar spine as well as involvement of the right mandibular condyle and clavicle. Percutaneous biopsy of the L1 spinal lesion confirmed metastatic PGL and the patient underwent posterior tumor resection and instrumented fusion of T7-T11. Postoperatively the patient was found to have a pathogenic SDHB deletion. Patients with SDHx mutation, particularly SDHB, have increased risk of developing metastatic PGLs. Consequently, these individuals require long-term surveillance given the risk for developing new tumors or disease recurrence, even years to decades after primary tumor resection. Surgical management of spinal metastatic PGL involves correcting spinal instability, minimizing tumor burden, and alleviating epidural cord compression. In patients with metastatic PGL of the spine, genetic testing should be considered.

A case of chronic postural tachycardia syndrome with positive anti-ganglionic acetylcholine receptor (gAChR) antibody

Postural orthostatic tachycardia syndrome (POTS) is a form of orthostatic intolerance characterized by symptoms such as lightheadedness, fainting, and brain fog that occur with a rapid elevation in heart rate when standing up from a reclining position. The etiology of POTS has yet to be established. However, a growing body of evidence suggests that POTS may be an autoimmune disorder such as autoimmune autonomic ganglionopathy, an acquired, immune-mediated form of diffuse autonomic failure. Many patients have serum antibodies that bind to the ganglionic acetylcholine receptors (gAChRs) in the autonomic ganglia. Herein, we describe a 39-year-old female patient with an eight-year history of orthostatic intolerance. POTS was diagnosed based on the findings of a head-up tilt test, in which a rapid increase in the patient's heart rate from 58 bpm in the lying position to 117 bpm in the upright position without orthostatic hypotension was observed. The POTS symptoms were refractory to various medications except for pyridostigmine bromide, which resulted in a partial resolution of her symptoms. Her serum was found to be strongly positive for anti-gAChR (β4 subunit) autoantibody (2.162 A.I., normal range: below 1.0). Based on these findings, a limited form of autoimmune POTS was diagnosed. After obtaining written informed consent, she was treated with intravenous immunoglobulin (IVIg) 400 mg/kg/day for five days, which led to clinical improvement by reducing her heart rate increase in the upright position. She was able to return to work with IVIg treatment at regular intervals. Our case provides further evidence of a potential autoimmune pathogenesis for POTS. Aggressive immunotherapy may be effective for POTS even in chronic cases.

Study of properties and applications nicotine alkaloids

Nicotine = Nicotine may be a plant alkaloid, found within the tobacco plant, and addictive focal sensory system (CNS) energizer that causes either ganglionic incitement in low portions or ganglionic blockage in high dosages. Nicotine goes about as an agonist at the nicotinic cholinergic receptors within the autonomic ganglia, at neuromuscular intersections, and within the medulla and therefore the mind. Nicotine&#39;s CNS-animating exercises could be intervened through the arrival of a couple of synapses, including acetylcholine, beta-endorphin, dopamine, norepinephrine, serotonin, and ACTH. Subsequently, fringe vasoconstriction, tachycardia, and raised pulse could be seen with nicotine admission. This specialist may likewise animate the chemoreceptor trigger zone, subsequently instigating queasiness and spewing.

Catecholamine-induced cardiomyopathy: an endocrinologist's perspective.

Although many endocrine diseases can be associated with acquired cardiomyopathy and heart failure, conditions except hypothyroidism, hyperthyroidism, phaeochromocytoma-paraganglioma (PPGL), and primary hyperaldosteronism are rare. PPGL is a rare catecholamine-secreting neuroendocrine tumour arising from the adrenal gland in 80-85% or extra-adrenal chromaffin cells of the autonomic neural ganglia in the remainder. The annual incidence of PPGL is 3-8 cases per million per year in the general population. Catecholamine-induced cardiomyopathy (CICMP) has got a prevalence of 8-11% among patients with PPGL. Hypertension, either sustained or episodic, is present in the vast majority (95%) of PPGL patients. However, among patients with CICMP, hypertension is present only in 65% of cases and the classical triad of paroxysmal headache, sweating, and palpitation is present only in 4%. Based on the cardiac remodelling in response to endogenous catecholamine excess, PPGL patients might present with one of the three CICMPs, including dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), or Takotsubo cardiomyopathy (TCM). Regardless of the subtypes, all CICMPs have many features in common - a dramatic clinical presentation, reversible cardiomyopathy, similar repolarisation electrocardiography changes, mild-moderate cardiac biomarker elevation, and normal coronary arteries on coronary angiography. CICMP should be suspected in patients with non-ischaemic, non-valvular forms of cardiomyopathy, even in those without definite features of catecholamine excess. PPGL associated TCM should be suspected in all acute coronary syndrome (ACS) patients exhibiting pronounced blood pressure variability with no culprit lesions on coronary angiography. This article will provide a review of the various CICMPs, their pathophysiology, clinical features, and the management options.

Multi-scale Order Recurrence Plot based deterministic analysis on Heart Rate Variability in Congestive Heart Failure Assessment

Congestive heart failure (CHF) is a cardiovascular disease associated with the abnormal autonomic nervous system (ANS). Heart rate variability analysis (HRV) is the main method for the quantitative evaluation of autonomic nervous function. Common analytical methods of HRV include time domain, frequency domain, and nonlinear methods. However, these methods generally ignore the short-term volatility of heart rate and autonomic ganglion law. Therefore, this study proposes a new parameter to analyze heart rate variability-determination of a multi-scale order recurrence plot (MSORP_DET). This method can analyze the HRV in patients with heart failure on multiple time scales. This study analyzed the R-R interval in 24-hour HRV data from 98 samples (54 normal subjects and 44 patients with CHF). The results showed that MSORP_DET could significantly distinguish CHF patients from normal subjects (p&lt;0.001). Moreover, the accuracy rate of screening patients with CHF reached the maximum of 81.6% by using the combination of low frequency/high frequency (LF/HF) and MSORP_DET, compared with 78.6% when using LF/HF alone. Therefore, MSORP_DET can be used as a new index to screen patients with CHF and reveal that the rhythm of ANS in patients with heart failure is more complex than that in normal people.

Neurons populating the rectal extrinsic nerves in humans express neuronal and Schwann cell markers

AbstractBackgroundIn mice, Schwann cell (SC) progenitors give rise to autonomic ganglion cells and migrate into the gut to become enteric neurons. It is unknown whether SC progenitors have a similar fate in humans. In search of evidence for human SC‐derived neurogenesis in the gastrointestinal (GI) tract, we studied the rectums from cadaveric controls and children with anorectal malformations (ARM).MethodsWe analyzed distal rectal tissue taken at autopsy from 10 children with normal GI tracts and resected rectal specimens in 48 cases of ARM. Of these specimens, 6 had neurons within the extrinsic rectal innervation. These were further investigated with immunohistochemistry for neuronal and SC/glial markers.Key ResultsPerirectal tissue from control and ARM contained GLUT1‐positive extrinsic nerves, many containing neurons. SC/glial markers (SOX10, CDH19, and PLP1) were expressed by glia in the enteric nervous system and perirectal nerves, while MPZ predominated only in glia of perirectal nerves, in both control and ARM. Neurons in perirectal nerves were 61% larger in ARM samples and co‐expressed SOX10 (81%), PLP1 (73%), and CDH19 (56%). In ARM, cytoplasmic SOX10 was co‐expressed with neuronal antigens in ~57% of submucosal and myenteric neurons, vs. ~3% in control. Furthermore, intrinsic gut neurons in ARM specimens co‐expressed PLP1 (18%) and CDH19 (18%); however, neuronal co‐expression of PLP1 and CDH19 was rarely (&lt;2%) observed in controls.Conclusions &amp; InferencesDual expression of glial and neuronal markers in rectal and perirectal neurons support a model of Schwann cell‐derived neurogenesis in the innervation of the human GI tract.

Emerging Therapies in Pheochromocytoma and Paraganglioma: Immune Checkpoint Inhibitors in the Starting Blocks.

Pheochromocytoma and paraganglioma are neuroendocrine neoplasms, originating in the adrenal medulla and in parasympathetic and sympathetic autonomic nervous system ganglia, respectively. They usually present as localized tumours curable with surgery. However, these tumours may exhibit heterogeneous clinical course, ranging from no/minimal progression to aggressive (progressive/metastatic) behavior. For this setting of patients, current therapies are unsatisfactory. Immune checkpoint inhibitors have shown outstanding results for several types of solid cancers. We therefore aimed to summarize and discuss available data on efficacy and safety of current FDA-approved immune checkpoint inhibitors in patients with pheochromocytoma and paraganglioma. After an extensive search, we found 15 useful data sources (four full-published articles, four supplements of scientific journals, seven ongoing registered clinical trials). The data we detected, even with the limit of the small number of patients treated, make a great expectation on the therapeutic use of immune checkpoint inhibitors. Besides, the newly detected predictors of response will (hopefully) be of great helps in selecting the subset of patients that might benefit the most from this class of drugs. Finally, new trials are in the starting blocks, and they are expected to shed in the next future new light on a therapy, which is considered a milestone in oncology.

PARAGANGLIOMA OF LUMBAR SPINE – A RARE CASE REPORT

Paragangliomas are neuroendocrine neoplasm. These neoplasms originate from specialized neural crest cells and have association with segmental or collateral autonomic ganglia. Spinal paraganglioma is rare tumor. We are presenting a case of spinal paraganglioma in a 58 years old male presented with low back pain, his MRI spine showed extramedullary intradural tumor at the level of L1-L2 vertebra .Tumor was excised and patient was discharged after uneventful stay at hospital. Paragangliomas are WHO grade I slow growing tumor, radiologically paraganglioma resembles other lesions, such as schwannomas, ependymomas, meningiomas. Gross total resection of tumor is treatment of choice .Prognosis is good with very rare recurrence rate.

Anatomical evidence for the efferent pathway from the hypothalamus to autonomic innervation in the anterior chamber structures of eyes

The autonomic innervation in the anterior chamber (AC) structures might play an efferent role in neural intraocular pressure (IOP) regulation, the center of which is thought to be located in the hypothalamus. In this study, we identified the efferent pathway from the hypothalamus to the autonomic innervation in the AC structures. Retrograde trans-multisynaptic pseudorabies virus (PRV) expressing green or red fluorescent protein, PRV531 and PRV724, was injected into the right and left AC of five rats, respectively; PRV531 was injected into the right AC of another five rats, and a non-trans-synaptic tracer, FAST Dil, was injected into the right AC of five rats as a control. Fluorescence signals in autonomic ganglia,the spinal cord and the central nervous system (CNS) were observed. Seven days after FAST Dil right AC injection, FAST Dil-labeled neurons were observed in the ipsilateral autonomic ganglia, including the superior cervical ganglion, pterygopalatine ganglion, and ciliary ganglion, but not in the CNS. Four and a half days after PRV531 injection into the right AC, PRV531-labeled neurons could be observed in the ipsilateral autonomic ganglia and bilateral hypothalamus nuclei, especially in the suprachiasmatic nucleus, paraventricular nucleus, dorsomedial hypothalamus, perifornical hypothalamus and ventral mammillary nucleus. Fluorescence signals of PRV531 mainly located in the ipsilateral autonomic preganglionic nuclei (Edinger-Westphal nucleus, superior salivatory nucleus and intermediolateral nucleus), but not in sensory trigeminal nuclei. Four and a half days after PRV531 right AC injection and PRV724 left AC injection, PRV531-labeled, PRV724-labeled, and double-labeled neurons could be observed in the above mentioned bilateral hypothalamus nuclei; but few contralateral infection-involving neurons (including double-labeled neurons) could be detected in the autonomic preganglionic nuclei. Our results indicate that there exist a both crossed and uncrossed hypothalamo-pre-parasympathetic and -pre-sympathetic tracts in the efferent pathways between the bilateral hypothalamic nuclei and the autonomic innervation of the bilateral AC.

Mitochondrial α7 nicotinic acetylcholine receptors are displaced from complexes with VDAC1 to form complexes with Bax upon apoptosis induction.

Nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic transmission in muscles and autonomic ganglia and regulate cytokine and neurotransmitter release in the brain and non-excitable cells. The α7 nAChRs localized in the outer membrane of mitochondria regulate cytochrome c release stimulated by apoptosis-inducing agents. However, the mechanisms through which nAChRs influence mitochondrial permeability remain obscure. Here we put an aim to explore the interaction of nAChRs with voltage-dependent anion channels (VDAC1) and pro-apoptotic protein Bax in the course of apoptosis induction. By using molecular modeling in silico, it was shown that both Bax and VDAC1 can bind within the 4th transmembrane portion (M4) of nAChR subunits. Experimentally, α7 nAChR-Bax and α7 nAChR-VDAC1 complexes were identified by sandwich ELISA in mitochondria isolated from astrocytoma U373 cells. Stimulating apoptosis of U373 cells by H2O2 disrupted α7-VDAC complexes and favored formation of α7-Bax complexes accompanied by cytochrome c release from mitochondria. α7-selective agonist PNU282987 or type 2 positive allosteric modulator PNU120596 disrupted α7-Bax and returned α7 nAChR to complex with VDAC1 resulting in attenuation of cytochrome c release. It is concluded that mitochondrial nAChRs regulate apoptosis-induced mitochondrial channel formation by modulating the interplay of apoptosis-related proteins in mitochondria outer membrane.

A review on iatrogenic botulism

Background:With the flourishing application of botulinum toxin cosmetically and therapeutically is the emergence of iatrogenic botulism, a new type of botulism in addition to the traditional ones.Objectives:We aim at a comprehensive review of the clinical characteristics of iatrogenic botulism. Methods: The available publications are retrieved and studied.Results:Botulinum toxin blocks cholinergic transmission in the neuromuscular junctions and autonomic ganglia. The blockade can spread from the site of tissue injection to adjacent or sometimes far off structures, resulting in inadvertent disabling or even lethal effects. On literature review, weakness and dysphagia are the commonest complications of iatrogenic botulism, whereas ophthalmological and oropharyngeal symptoms are more prevalent in the cosmetic group and dyspnea in the therapeutic group. Antitoxin therapy is required in about 20% of the patients. Diagnosis of iatrogenic botulism is primarily clinical and should not be confused with the neurological diagnoses possessing similar clinical manifestations. Vigilance to the drug formulation, dosage, and administration during botulinum toxin injection are part of the preventive measures in minimizing the occurrence of iatrogenic botulism.Conclusion:While overlapping with the traditional types of botulism, iatrogenic botulism carries its unique clinical characteristics.

The role of the tripartite synapse in the heart: how glial cells may contribute to the physiology and pathophysiology of the intracardiac nervous system.

One of the major roles of the intracardiac nervous system (ICNS) is to act as the final site of signal integration for efferent information destined for the myocardium to enable local control of heart rate and rhythm. Multiple subtypes of neurons exist in the ICNS where they are organized into clusters termed ganglionated plexi (GP). The majority of cells in the ICNS are actually glial cells; however, despite this, ICNS glial cells have received little attention to date. In the central nervous system, where glial cell function has been widely studied, glia are no longer viewed simply as supportive cells but rather have been shown to play an active role in modulating neuronal excitability and synaptic plasticity. Pioneering studies have demonstrated that in addition to glia within the brain stem, glial cells within multiple autonomic ganglia in the peripheral nervous system, including the ICNS, can also act to modulate cardiovascular function. Clinically, patients with atrial fibrillation (AF) undergoing catheter ablation show high plasma levels of S100B, a protein produced by cardiac glial cells, correlated with decreased AF recurrence. Interestingly, S100B also alters GP neuron excitability and neurite outgrowth in the ICNS. These studies highlight the importance of understanding how glial cells can affect the heart by modulating GP neuron activity or synaptic inputs. Here, we review studies investigating glia both in the central and peripheral nervous systems to discuss the potential role of glia in controlling cardiac function in health and disease, paying particular attention to the glial cells of the ICNS.

Porphyric Neuropathy: Pathophysiology, Diagnosis, and Updated Management.

To review the peripheral neurological complications of the acute hepatic porphyrias, as well as the latest advances in their pathophysiology and management. The diagnosis of porphyric neuropathy remains challenging as varying neuropathic patterns are encountered depending on disease stage, including a non-length-dependent distribution pattern. The major pathophysiologic mechanism is δ-aminolevulinic acid (ALA)-induced neurotoxicity. The less restrictive blood-nerve barrier in the autonomic ganglia and myenteric plexus may explain the frequency of dysautonomic manifestations. Recently, a prophylactic small interfering RNA (siRNA)-based therapy that reduces hepatic ALA Synthase-1 mRNA was approved for patients with recurrent neuro-visceral attacks. Neurologists should appreciate the varying patterns of porphyric neuropathy. As with most toxin-induced axonopathies, long-term outcomes depend on early diagnosis and treatment. While the short-term clinical and biochemical benefits of siRNA-based therapy are known, its long-term effects on motor recovery, chronic pain, and dysautonomic manifestations are yet to be determined.

AUTONOMIC INSTABILITY SECONDARY TO GLOMUS VAGALE PARAGANGLIOMA

Introduction Paragangliomas are rare vascular neuroendocrine tumors that arise from neural crest chromaffin cells that are associated with autonomic ganglion. A small subset of these tumors are found in the head and neck region and originate in the carotid and aortic bodies. Case description A 60-year-old woman presents with recurrent near syncopal episodes for 3 days associated with loss of appetite and 20-pound weight loss for 2 months. Two years ago, the patient presented with similar presyncopal episodes and Holter monitoring at that time showed multiple pauses up to 20 seconds, after which she was referred for dual chamber pacemaker implantation. During that time, a tilt table test and finometer measuring beat to beat blood pressure values was positive for sudden episodic hypotension and bradycardia every 2-3 minutes and were associated with lightheadedness and near syncope. Vitals during hospitalization showed BP ranging from 80s/50s to 130s/80s. Physical exam showed normal cardiopulmonary findings but revealed a right cervical mass along the angle of mandible, mildly tender to palpation. EKG showed an appropriately paced atrial rhythm at 59 beats per minute without any other abnormalities. As a result of her hypotensive episodes, the patient was started on fludrocortisone and pyridostigmine. CT neck with contrast showed a post styloid compartment mass with significant compression of R internal jugular vein and branches of R carotid artery. Subsequent angiography showed 4 × 3 × 3 cm. hypervascular mass in the upper right neck with displacement of carotid arteries and AV shunting into the R internal jugular vein. Findings were consistent with Glomus Vagale Paraganglioma and patient was discharged in stable condition for outpatient evaluation for surgical resection of mass. Discussion Indistinguishable from pheochromocytomas at the cellular level, paragangliomas are divided into catecholamine secreting sympathetic and nonfunctional parasympathetic neoplasms. Although most cases are sporadic, there is a link between paragangliomas and mutation of genes coding for Succinate Dehydrogenase (SDH) enzyme, Von Hippel Lindau, MEN2, and NF1 syndromes. Paragangliomas are usually asymptomatic and present as painless cervical masses. Glomus vagale, a particularly rare type of paraganglioma located near the vagus nerve, can present with tinnitus, dysphagia, or hoarseness. Carotid sinus compression by the cervical mass can lead to symptomatic hypotension and bradycardia, as seen in our case. The diagnosis of non-secretory paragangliomas includes 24-hour urine test to measure catecholamine and metanephrine levels and visualization of tumor via ultrasound, CT, or MRI which can show a “salt and pepper” appearance due to micro hemorrhage and hypervascularization. Treatment includes surgery, embolization, or radiotherapy. Conclusion Paragangliomas are uncommon tumors with glomus paragangliomas being a rare subtype. Because of their cellular composition and anatomic locations, they often cause autonomic instability. Further research should be performed to improve diagnosis and treatment.