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A 5-year-old Arabian broodmare with acute colic was diagnosed with lymphocytic ganglioneuritis of the coeliac-mesenteric ganglia and lymphocytic‒plasmacytic enterocolitis resembling inflammatory bowel disease. No significant pathogens were identified by aerobic culture or histopathological examination. The ganglia were multifocally infiltrated with small lymphocytes that were immunopositive for CD3 and negative for CD20 and CD79a antigens, indicating CD3 + T-lymphocyte-mediated coeliac-mesenteric ganglioneuritis. The findings suggest immune-mediated inflammatory bowel disease resulting in disturbance of the autonomic nervous system in the gastrointestinal tract, as in ulcerative colitis in humans. Histopathological features in this case differ from those of equine enteric dysautonomia and chronic intestinal pseudo-obstruction, which are characterized by neuronal degeneration and inflammation, respectively, and mostly affect the mural ganglion plexuses. To the best of our knowledge, this is the first report of CD3 + T-lymphocytic extramural enteric ganglioneuritis in equine inflammatory bowel disease., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In sporadic Creutzfeldt-Jakob disease (sCJD), the pathological changes appear to be restricted to the central nervous system. Only involvement of the trigeminal ganglion is widely accepted. The present study systematically examined the involvement of peripheral ganglia in sCJD utilizing the currently most sensitive technique for detecting prions in tissue morphologically. The trigeminal, nodose, stellate, and celiac ganglia, as well as ganglia of the cervical, thoracic and lumbar sympathetic trunk of 40 patients were analyzed with the paraffin-embedded tissue (PET)-blot method. Apart from the trigeminal ganglion, which contained protein aggregates in five of 19 prion type 1 patients, evidence of prion protein aggregation was only found in patients associated with type 2 prions. With the PET-blot, aggregates of prion protein type 2 were found in all trigeminal (17/17), in some nodose (5 of 7) and thoracic (3 of 6) ganglia, as well as in a few celiac (4 of 19) and lumbar (1 of 5) ganglia of sCJD patients. Whereas aggregates of both prion types may spread to dorsal root ganglia, more CNS-distant ganglia seem to be only involved in patients accumulating prion type 2. Whether the prion type association is due to selection by prion type-dependent replication, or due to a prion type-dependent property of axonal spread remains to be resolved in further studies., (© 2021. The Author(s).)

Median Arcuate Ligament Syndrome (MALS) is a rare entity characterized by severe post-prandial epigastric pain, nausea, vomiting, and/or weight loss. Symptoms have been attributed to vascular compression (celiac artery compression syndrome, CACS), but it remains controversial whether they could be secondary to neural compression. Literature review identified rare description of pathologic findings in surgery journals. The clinico-pathologic findings of four MALS patients who underwent robotic or laparoscopic surgery in our hospital are described. All our patients were female with a median age of 32.5 (range 25-55 years), and a median BMI of 23.5 kg/m 2 . They presented with chronic often post-prandial abdominal pain (4/4), nausea (3/4), emesis (2/4), anorexia (1/4), and weight loss (1/4). Two patients had a history of Crohn's disease. At intraoperative exploration, the celiac artery and adjacent nerves and ganglia were encased and partially compressed by fibrotic tissue in each patient. In each case laparoscopic excision of fibrotic tissue, celiac plexus and ligament division and was performed; celiac plexus nerve block was also performed in one patient. After surgical intervention, symptoms improved in three of the patients whose specimens show periganglionic and perineural fibrosis with proliferation of small nerve fibers. Our findings support neurogenic compression as a contributing factor in the development of pain and other MALS symptoms, and favor the use of MALS rather than CACS as diagnostic terminology. To further study the pathogenesis of this unusual syndrome, surgeons should submit all tissues excised during MALS procedures for histopathologic examination., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In a study originally designed to find potential risk factors for bovine spongiform encephalopathy (BSE) we examined tissues from 403 Holstein Frisian cattle in total. These included 20 BSE cattle and their 236 birth- and feeding cohort animals plus 32 offspring, 103 age, breed and district-matched control cattle and further twelve cattle with neurological signs. In addition to the obex, we examined the celiac ganglion, cervical cranial ganglion, trigeminal ganglion and proximal ganglion of the vagus nerve using histological techniques. Unexpectedly, we found a high number of neurofibroma, a benign peripheral nerve sheath tumor consisting of Schwann cells, fibroblasts and perineural cells. The neurofibroma were present only in the celiac ganglion and found during histologic examination. With a frequency of 9.91% in BSE cattle and their cohorts (case animals) and 9.09% in the age, breed and district matched control animals there seems to be no correlation between the occurrence of BSE and neurofibroma. Benign peripheral nerve sheath tumors have been described more often in cattle than in other domestic animals. Usually, they are incidental macroscopic findings in the thoracic ganglia during meat inspection. To our knowledge, there are no previous systematic histologic studies including bovine celiac ganglia at all. The high incidence of celiac ganglia neurofibroma may play a role in the frequently occurring abomasal displacements in Holstein Frisian cattle as the tumors might cause a gastrointestinal motility disorder. At present a genetic predisposition for these neoplasms cannot be ruled out.

Background: Pre-operative staging of pancreatic adenocarcinoma guides clinical decision making. Limited data indicate that metastasis to celiac ganglia (CG) correlates with poor prognosis. We investigated feasibility and safety of endoscopic ultrasound fine needle aspiration (EUS-FNA) detection of CG metastasis and its impact upon tumor stage, resectability, and survival in pancreatic ductal adenocarcinoma (PDAC)., Patients: We reviewed our prospectively maintained EUS and cytopathology databases to identify patients with FNA proven CG metastasis in patients with PDAC from 2004 to 2017. Clinical demographics, EUS, CT, MRI, cytopathology, cancer stage, and resectability data were analyzed. Survival of PDAC patients with CG metastasis was compared to the expected survival of PDAC patients of similar stage as reported by the United States National Cancer Database., Results: Twenty-one patients with PDAC [median age 73 (IQR63-78); 14 (67%) female)], had CG metastasis confirmed by cytopathologic assessment. CG metastasis resulted in tumor upstaging relative to other EUS findings and cross sectional imaging findings in 12 (57%) and 15 (71%) patients, and converted cancers from resectable to unresectable relative to EUS and cross sectional imaging in 7 (37%) and 7 (37%) patients, respectively. In patients with PDAC, the survival of patients with CG metastasis was not significantly different from the overall survival (hazard ratio 0.71; 95% confidence interval 0.44, 1.13; p = 0.15)., Conclusions: EUS-FNA may safely identify CG metastases. While CG metastasis upstaged and altered the resectability status among this cohort of patients with PDAC, the survival data with regard to PDAC suggest that this may be misguided., Competing Interests: Declaration of competing interest All authors having nothing to disclose., (Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

T-cell immune attack of cancer cells underlies the efficacy of immune checkpoint inhibitors in many cancer subtypes, but is not yet well established in the primary brain cancer glioblastoma. Immune checkpoint inhibitor treatments that disinhibit the immune system to enhance immune clearance of cancer have in rare cases resulted in T-cell attack of peripheral ganglia causing lymphocytic ganglionitis. In glioblastoma, lymphocytic ganglionitis has not been reported and checkpoint inhibitors are not routinely used. Here we report a case of glioblastoma not treated with checkpoint inhibitors in which the primary tumor and peripheral ganglia of the celiac and sympathetic chains, as well as myenteric plexus, are infiltrated by CD8 + cytotoxic T-cells. In addition to the marked lymphocytic infiltrates, this case is also notable for an unusually long survival (8 years) after diagnosis with glioblastoma, but an ultimately fatal outcome due to ileus. The findings suggest T-cell immune attack of glioblastoma may prolong survival, but also suggest T-cell autoimmune diseases such as lymphocytic ganglionitis could become a risk with the future use of immune-targeted therapies for glioblastoma., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background Detectable uptake of 68Ga-PSMA-ligands in sympathetic ganglia may potentially lead to mistaking them for malignant lesions. Our aim was to investigate the anatomy of cervico-thoracic-ganglia-complex (CTG-C) in the MR part of multimodal 68Ga-PSMA-11 PET/MR imaging, in view of PET factors hindering its proper identification. Patients and methods In 106 patients, 212 sites of the CTG-C were retrospectively reviewed to assess the radiotracer uptake (SUVmax), size, shape, position, symmetry of location and visual uptake intensity. Asymmetry of PSMA-ligand uptake and increased uptake were regarded as risk factors of malignancy. Results In 66.0% left (L) and 53.8% right (R) CTG-C we noticed configurations, resembling the shape of an exclamation-mark, a question-mark, or its part (called "typical"). Tumor-like CTG-C shapes (oval, binodular or longitudinal) were detected in 28.3% L-CTG-C and in 40.6% R-CTG-C. When visual assessment of PET suggested malignancy, the recognition of "typical" shape of underlying CTG-C on MR generated a rise in the accuracy of their proper identification (from 34.4% to 75%, χ2(1) = 70.4; p < 0.001). Recognizing the shape of the CTG-C as "typical" in MR allowed us to classify as "not-suspicious" 61.9% of all CTG-C which were treated as "suspicious" after sole PET assessment. Conclusions The characteristic shape of cervico-thoracic-ganglia-complex (resembling a question-mark, or its part) helps in proper recognition of CTG-C on multimodal whole-body 68Ga-PSMA-ligand PET/MR imaging, when detectable uptake might lead to considering pathology.

Bladder cystopathy and autonomic dysfunction are common complications of diabetes, and have been associated with changes in ganglionic transmission and some measures of neuronal excitability in male mice. To determine whether type II diabetes also impacts excitability of ganglionic neurons in females, we investigated neuronal excitability and firing properties, as well as underlying ion channel expression, in major pelvic ganglion (MPG) neurons in control, 10-week, and 21-week Lepr db/db mice. Type II diabetes in Lepr db/db animals caused a non-linear change in excitability and firing properties of MPG neurons. At 10 weeks, cells exhibited increased excitability as demonstrated by an increased likelihood of firing multiple spikes upon depolarization, decreased rebound spike latency, and overall narrower action potential half-widths as a result of increased depolarization and repolarization slopes. Conversely, at 21 weeks MPG neurons of Lepr db/db mice reversed these changes, with spiking patterns and action-potential properties largely returning to control levels. These changes are associated with numerous time-specific changes in calcium, sodium, and potassium channel subunit mRNA levels. However, Principal Components Analysis of channel expression patterns revealed that rectification of excitability is not simply a return to control levels, but rather a distinct ion channel expression profile in 21-week Lepr db/db neurons. These data indicate that type II diabetes can impact the excitability of post-ganglionic, autonomic neurons of female mice, and suggest that the non-linear progression of these properties with diabetes may be the result of compensatory changes in channel expression that act to rectify disrupted firing patterns of Lepr db/db MPG neurons., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Neuroblastoma ranks third among pediatric malignancies., Case Report: The case of a 3-year-old child is presented, who suddenly had frequent, unproductive, emetic cough; fever; and weight loss. Lung X-ray showed an opacity situated in the posterior superior mediastinum. Thoracic ultrasound revealed a slightly inhomogeneous, hypoechoic mass located in the posterior superior mediastinum. Computed tomography evidenced a tumor mass with homogeneous appearance in the costo-vertebral groove. Histological examination confirmed the diagnosis of ganglioneuroblastoma., Conclusion: Although history and clinical examination provided few elements, diagnosis was made based on imaging and histopathological examination.

Equine dysautonomia (grass sickness) is characterized by autonomic neuronal degeneration and is often fatal. As outbreaks occur, rapid diagnosis is essential but confirmation currently requires histological examination. This study evaluated diagnostic accuracy of cytological examination of cranial cervical ganglion (CCG) scrapings for dysautonomia diagnosis. CCG smears from 20 controls and 16 dysautonomia cases were stained with May-Grünwald Giemsa (MGG), hematoxylin and eosin (HE), and cresyl fast violet (CFV), with HE-stained histological sections of CCG as gold standard for diagnosis. Examining all 3 stains together, the sensitivity and specificity were 100%. Occasional individual smears (4/107, 3.7%) were nondiagnostic due to low cellularity, and in a few individual smears the final diagnosis was correct but more tentative (CFV: 5/33 [15.1%], HE: 2/34 [5.9%], and MGG: 4/36 [11.1%]), due to low cellularity or suboptimal cell morphology. CCG cytology was considered reliable for rapid postmortem diagnosis of equine dysautonomia, particularly using MGG.

Background: Studies have shown regional and functional selectivity of cardiac postganglionic neurones indicating there might exist a similar heterogeneity in spinal segmental preganglionic neurones, which requires further investigation., Methods: Right and left sympathetic chains were electrically stimulated from T6 to T1 in the innervated isolated rabbit heart preparation (n = 18). Sinus rate, left ventricular pressure, retrograde ventriculo-atrial conduction, monophasic action potential duration, effective refractory period, ventricular fibrillation threshold and electrical restitution were measured., Results: Right sympathetic stimulation had a greater influence on heart rate (T1-T2: right; 59.9 ± 6.0%, left; 41.1 ± 5.6% P < 0.001) and left stimulation had greater effects on left ventricular pressure (T1-T2: right; 20.7 ± 3.2%, left; 40.3 ± 5.4%, P < 0.01) and ventriculo-atrial conduction (T1-T2: right; -6.8 ± 1.1%, left; -15.5 ± 0.2%) at all levels, with greater effects at rostral levels (T1-T3). Left sympathetic stimulation caused shorter monophasic action potentials at the base (T4-T5: right; 119.3 ± 2.7 ms, left; 114.7 ± 2.5 ms. P < 0.05) and apex (T4-T5: right; 118.8 ± 1.2 ms, left; 114.6 ± 2.6 ms. P < 0.05), greater shortening of effective refractory period (T4-T5: right; -3.6 ± 1.3%, left; -7.7 ± 1.8%. P < 0.05), a steeper maximum slope of restitution (T4-T5 base: right; 1.3 ± 0.2, left; 1.8 ± 0.2. P < 0.01. T4-T5 apex: right; 1.0 ± 0.2, left; 1.6 ± 0.3. P < 0.05) and a greater decrease in ventricular fibrillation threshold (T4-T5: right; -22.3 ± 6.8%, left;-39.0 ± 1.7%), with dominant effects at caudal levels (T4-T6)., Conclusions: The preganglionic sympathetic efferent axons show functionally distinct pathways to the heart. The caudal segments (T4-T6) of the left sympathetic chain had a greater potential for arrhythmia generation and hence could pose a target for more focused clinical treatments for impairments in cardiac function., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Lewy body forms of primary chronic autonomic failure (CAF) such as incidental Lewy body disease (ILBD), Parkinson's disease (PD), and pure autonomic failure evolving into dementia with Lewy bodies (PAF+DLB) feature cardiac sympathetic denervation, whereas multiple system atrophy (MSA) in most cases does not. What links Lewy bodies with cardiac sympathetic denervation in CAF? In familial PD, abnormalities of the alpha-synuclein (AS) gene cause CAF and cardiac sympathetic denervation; and in sporadic PD, brainstem Lewy bodies contain AS co-localized with tyrosine hydroxylase (TH), a marker of catecholaminergic neurons. Cytotoxicity from AS deposition within sympathetic neurons might explain noradrenergic denervation in Lewy body forms of CAF. We used immunofluorescence microscopy (IM) to explore this possibility in sympathetic ganglia obtained at autopsy from CAF patients., Methods: Immunoreactive AS and TH were imaged in sympathetic ganglion tissue from 6 control subjects (2 with ILBD), 5 PD patients (1 with concurrent PSP), and 3 patients with CAF (2 PAF + DLB, 1 MSA)., Results: MSA involved normal ganglionic TH and no AS deposition. In ILBD TH was variably decreased, and TH and AS were co-localized in Lewy bodies. In PD TH was substantially decreased, and TH and AS were co-localized in Lewy bodies. In PAF + DLB TH was virtually absent, but AS was present in Lewy bodies. The PD + PSP patient had AS co-localized with tau but not TH., Conclusions: Sympathetic denervation and intraneuronal AS deposition are correlated across CAF syndromes, consistent with a pathogenic contribution of synucleinopathy to cardiac noradrenergic deficiency in Lewy body diseases.

Injury to peripheral nerves can lead to neuropathic pain, along with well-studied effects on sensory neurons, including hyperexcitability, abnormal spontaneous activity, and neuroinflammation in the sensory ganglia. Neuropathic pain can be enhanced by sympathetic activity. Peripheral nerve injury may also damage sympathetic axons or expose them to an inflammatory environment. In this study, we examined the lumbar sympathetic ganglion responses to two rat pain models: ligation of the L5 spinal nerve, and local inflammation of the L5 dorsal root ganglion (DRG), which does not involve axotomy. Both models resulted in neuroinflammatory changes in the sympathetic ganglia, as indicated by macrophage responses, satellite glia activation, and increased numbers of T cells, along with very modest increases in sympathetic neuron excitability (but not spontaneous activity) measured in ex vivo recordings. The spinal nerve ligation model generally caused larger responses than DRG inflammation. Plasticity of the sympathetic system should be recognized in studies of sympathetic effects on pain.

Purpose: Primary hyperhidrosis is a pathological disorder of unknown etiology, affecting 0.6-5% of the population, and causing severe functional and social handicaps. As the etiology is unknown, it is not possible to treat the root cause. Recently some differences between affected and non-affected people have been reported. The aim of this review is to summarize these new etiological data., Methods: Search of the literature was performed in the PubMed/Medline Database and pertinent articles were retrieved and reviewed. Additional publications were obtained from the references of these articles., Results: Some anatomical and pathophysiological characteristics (as well as enzymatic, metabolic, and neurological dysfunctions) have been observed in hyperhidrotic subjects; three main possible etiological factors predominate. A familial trait seems to exist, and genetic loci associated with hyperhidrosis have been identified. Histological differences were observed in sympathetic ganglia of hyperhidrotic subjects: the ganglia were larger and contained a higher number of ganglion cells. A higher expression of acetylcholine and alpha-7 neuronal nicotinic receptor subunit in the sympathetic ganglia of patients with hyperhidrosis has been reported., Conclusions: Despite these accumulated data, the etiology of primary hyperhidrosis remains obscure. Nevertheless, three main lines for future research seem to be delineated: genetics, histological observations, and enzymatic studies.

The stellate ganglion is a common target to manage neuropathic pain in the upper extremities. However, the effect duration of a single stellate ganglion block is often temporary. To overcome the short-term effects of a single sympathetic block, pulsed radiofrequency (PRF) can be applied. The aim of the present study was to investigate the efficacy of PRF on the cervical sympathetic chain under ultrasound guidance for complex regional pain syndrome (CRPS).Twelve CRPS patients who underwent PRF on the cervical sympathetic chain were enrolled in this retrospective analysis. Under ultrasound guidance, PRF was performed for 420 seconds at 42°C on the C6- and C7-level sympathetic chain.The pain intensity decreased significantly at 1 week after the procedure. Overall, 91.7% of patients experienced at least moderate improvement. A positive correlation was observed between the extent of pain reduction at 1 week after PRF and the degree of overall benefit (r = 0.605, P = 0.037). This reduction in symptoms was maintained for a mean of 31.41 ± 26.07 days after PRF. There were no complications associated with this procedure.PRF on the cervical sympathetic chain, which can be performed easily and safely under ultrasound guidance, should be considered an option for managing CRPS of the upper extremities., Competing Interests: The authors have no funding and conflicts of interest to disclose.

The aim of the present study was to define changes in the expression of somatostatin (SOM) in the sympathetic perikarya innervating the porcine stomach prepyloric area during acetylsalicylic-acid-induced gastritis (ASA) and experimentally induced hyperacidity (HCL) and following partial stomach resection (RES). On day 1, the stomachs were injected with neuronal retrograde tracer Fast Blue (FB). Animals in the ASA group were given acetylsalicylic acid orally for 21 days. On the 22nd day after FB injection, partial stomach resection was performed in RES animals. On day 23, HCL animals were intragastrically given 5 ml/kg of body weight of a 0.25 M aqueous solution of hydrochloric acid. On day 28, all pigs were euthanized. Then, 14- μ m thick cryostat sections of the coeliac-superior mesenteric ganglion (CSMG) complexes were processed for routine double-labelling immunofluorescence. All pathological conditions studied resulted in upregulation of SOM-like (SOM-LI) immunoreactivity (from 14.97 ± 1.57% in control group to 33.72 ± 4.39% in the ASA group, to 39.02 ± 3.65% in the RES group, and to 29.63 ± 0.85% in the HCL group). The present studies showed that altered expression of SOM occurs in sympathetic neurons supplying the prepyloric area of the porcine stomach during adaptation to various pathological insults.

Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH) + neurons in the autonomic nuclei and superficial dorsal horn in L6-S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH) - and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH + neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D 2 -like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH + neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH + cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH + neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI., Competing Interests: The authors declare no competing financial interests., (Published by Elsevier Inc.)

The MYCN gene is amplified and overexpressed in a large proportion of high stage neuroblastoma patients and has been identified as a key driver of tumorigenesis. However, the mechanism by which MYCN promotes tumor initiation is poorly understood. Here we conducted metabolic profiling of pre-malignant sympathetic ganglia and tumors derived from the TH-MYCN mouse model of neuroblastoma, compared to non-malignant ganglia from wildtype littermates. We found that metabolites involved in the biosynthesis of glutathione, the most abundant cellular antioxidant, were the most significantly upregulated metabolic pathway at tumor initiation, and progressively increased to meet the demands of tumorigenesis. A corresponding increase in the expression of genes involved in ribosomal biogenesis suggested that MYCN-driven transactivation of the protein biosynthetic machinery generated the necessary substrates to drive glutathione biosynthesis. Pre-malignant sympathetic ganglia from TH-MYCN mice had higher antioxidant capacity and required glutathione upregulation for cell survival, when compared to wildtype ganglia. Moreover, in vivo administration of inhibitors of glutathione biosynthesis significantly delayed tumorigenesis when administered prophylactically and potentiated the anticancer activity of cytotoxic chemotherapy against established tumors. Together these results identify enhanced glutathione biosynthesis as a selective metabolic adaptation required for initiation of MYCN-driven neuroblastoma, and suggest that glutathione-targeted agents may be used as a potential preventative strategy, or as an adjuvant to existing chemotherapies in established disease., (Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.)

Gene therapy has played an integral role in advancing our understanding of the central nervous system. However, gene therapy techniques have yet to be widely utilized in the peripheral nervous system. Critical targets for gene therapy within the PNS are the neurons in sympathetic ganglia, which are the final pathway to end organs. Thus they are the most specific targets for organ-specific neuron modification. This presents challenges because neurons are not viscerotopically organized within the ganglia and therefore cannot be targeted by their location. However, organ-specific neurons have been identified in sympathetic ganglia of some species and this offers an opportunity for targeting and transducing neurons by way of their target. In fact, alterations in sympathetic neurons have had pathological effects, and transducing organ-specific sympathetic neurons offer an exciting opportunity to selectively modify sympathetic pathology. In this chapter, we describe a method to virally transduce the celiac ganglion (CG), a prevertebral sympathetic ganglion that innervates abdominal organs, with AAV serotypes 1 and 6; thereby, providing a potential avenue to modulate specific subsets of neurons within the celiac ganglion.

The RNA binding protein Lin28B is expressed in developing tissues and sustains stem and progenitor cell identity as a negative regulator of the Let-7 family of microRNAs, which induces differentiation. Lin28B is activated in neuroblastoma (NB), a childhood tumor in sympathetic ganglia and adrenal medulla. Forced expression of Lin28B in embryonic mouse sympathoadrenal neuroblasts elicits postnatal NB formation. However, the normal function of Lin28B in the development of sympathetic neurons and chromaffin cells and the mechanisms involved in Lin28B-induced tumor formation are unclear. Here, we demonstrate a mirror-image expression of Lin28B and Let-7a in developing chick sympathetic ganglia. Lin28B expression is not restricted to undifferentiated progenitor cells but, is observed in proliferating noradrenergic neuroblasts. Lin28 knockdown in cultured sympathetic neuroblasts decreases proliferation, whereas Let-7 inhibition increases the proportion of neuroblasts in the cell cycle. Lin28B overexpression enhances proliferation, but only during a short developmental period, and it does not reduce Let-7a. Effects of in vivo Lin28B overexpression were analyzed in the LSL-Lin28B(DBHiCre) mouse line. Sympathetic ganglion and adrenal medulla volume and the expression level of Let-7a were not altered, although Lin28B expression increased by 12- to 17-fold. In contrast, Let-7a expression was strongly reduced in LSL-Lin28B(DbhiCre) NB tumor tissue. These data demonstrate essential functions for endogenous Lin28 and Let-7 in neuroblast proliferation. However, Lin28B overexpression neither sustains neuroblast proliferation nor affects let-7 expression. Thus, in contrast to other pediatric tumors, Lin28B-induced NB is not due to expansion of proliferating embryonic neuroblasts, and Let-7-independent functions are implicated during initial NB development., Significance Statement: Lin28A/B proteins are highly expressed in early development and maintain progenitor cells by blocking the biogenesis and differentiation function of Let-7 microRNAs. Lin28B is aberrantly upregulated in the childhood tumor neuroblastoma (NB). NB develops in sympathetic ganglia and adrenal medulla and is elicited by forced Lin28B expression. We demonstrate that Lin28A/B and Let-7 are essential for sympathetic neuroblast proliferation during normal development. Unexpectedly, Lin28B upregulation in a mouse model does not affect neuroblast proliferation, ganglion size, and Let-7 expression during early postnatal development. Lin28B-induced NB, in contrast to other pediatric cancers, does not evolve from neuroblasts that continue to divide and involves Let-7-independent functions during initial development., (Copyright © 2015 the authors 0270-6474/15/3516532-14$15.00/0.)

Objectives: To evaluate the feasibility of ultrasound (US) detection of the middle cervical sympathetic ganglion (CSG)., Materials and Methods: We examined 52 consecutive patients with 104 bilateral middle CSGs. We identified middle CSG according to our sonographic assessment criteria. After finding oval-shaped hypoechoic structure on transverse scan, we verified a continuous, hypoechoic line connecting the bulbous structure at both sides. The basic US characteristics were evaluated using the size, location, relationship to the common carotid artery, and relationship to the inferior thyroidal artery., Results: The middle CSG was identified in 41% (43/104). The mean size of the middle CSG was 3.8±1.5 mm in width, 1.9±0.7 mm in height, and 8.7±3.2 mm in length. They were primarily located at the C6 level (41/43, 95%). Regarding the relationship with common carotid artery, 88% (38/43) were lateral type and 12% (5/43) were medial type. Regarding the relationship with the inferior thyroid artery, 34% (15/43) were anterior type, 26% (11/43) were posterior type, and 40% (17/43) were unable to access the relationship., Discussion: Direct visualization of middle CSG based on the understanding of both its location and US features may reduce complications and improve the accuracy of US-guided neck procedures.

Background: Schwannoma is a rare benign tumor derived from nerve sheaths. When derived from the cervical sympathetic chain, it usually presents itself as an asymptomatic mass located in the posterior cervical region, at paravertebral level. Its diagnosis is not easy, usually requiring multiple imaging tests. Its differential diagnosis includes parathyroid adenoma., Clinical Case: A new case of schwannoma of the cervical sympathetic chain in a patient with a synchronous overactive parathyroid adenoma is reported. This case adds to the sixty described in the literature, although to our knowledge no association between schwannoma and parathyroid adenoma has been reported to date., Conclusions: Despite being a benign tumor, its treatment is a complete surgical resection. The most common complication after the surgery needed for these tumors is ipsilateral Horner syndrome., (Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.)

Despite nerve-sparing radical prostatectomy, nerve damage and erectile dysfunction (ED) prevail, and preventing neurodegeneration is of great importance. Neurotrophic factors and neurite outgrowth were characterized in major pelvic ganglia (MPG) following bilateral cavernous nerve injury (BCNI). Young male Sprague-Dawley rats underwent sham or BCNI surgery, and the intracavernosal pressure to mean arterial pressure ratio was measured 2, 7, 14, 21, 30, and 60 days following injury (n = 8/group). MPG gene expression (qPCR) and Western blot were performed for glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurturin, neurotrophin (NT)-3, NT4, brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor, and activating transcription factor 3 (ATF3). Additional rats were injured, and MPGs were removed 24 hr, 48 hr, 3 days, and 7 days following BCNI (n = 3/group). MPGs were cultured in Matrigel, and neurite outgrowth was measured. Erections were impaired early and improved by 60 days in BCNI rats. GDNF, NGF, BDNF, and ATF3 gene expression was significantly increased and NT3 was decreased in MPGs following BCNI (48 hr to 21 days, P < 0.05). GDNF and NGF protein levels were elevated in 48-hr BCNI rats. MPG neurite outgrowth from 24-hr and 48-hr BCNI was higher than sham (658 ± 19 μm, 607 ± 24 μm, 393 ± 23 μm, respectively, P < 0.05). Further studies examining the roles of neurotrophic factors in modulating signaling pathways may provide therapeutic avenues for neurogenically mediated ED., (© 2015 Wiley Periodicals, Inc.)

Septic shock, the most severe complication associated with sepsis, is manifested by tissue hypoperfusion due, in part, to cardiovascular and autonomic dysfunction. In many cases, the splanchnic circulation becomes vasoplegic. The celiac-superior mesenteric ganglion (CSMG) sympathetic neurons provide the main autonomic input to these vessels. We used the cecal ligation puncture (CLP) model, which closely mimics the hemodynamic and metabolic disturbances observed in septic patients, to examine the properties and modulation of Ca2+ channels by G protein-coupled receptors in acutely dissociated rat CSMG neurons. Voltage-clamp studies 48 hr post-sepsis revealed that the Ca2+ current density in CMSG neurons from septic rats was significantly lower than those isolated from sham control rats. This reduction coincided with a significant increase in membrane surface area and a negligible increase in Ca2+ current amplitude. Possible explanations for these findings include either cell swelling or neurite outgrowth enhancement of CSMG neurons from septic rats. Additionally, a significant rightward shift of the concentration-response relationship for the norepinephrine (NE)-mediated Ca2+ current inhibition was observed in CSMG neurons from septic rats. Testing for the presence of opioid receptor subtypes in CSMG neurons, showed that mu opioid receptors were present in ~70% of CSMG, while NOP opioid receptors were found in all CSMG neurons tested. The pharmacological profile for both opioid receptor subtypes was not significantly affected by sepsis. Further, the Ca2+ current modulation by propionate, an agonist for the free fatty acid receptors GPR41 and GPR43, was not altered by sepsis. Overall, our findings suggest that CSMG function is affected by sepsis via changes in cell size and α2-adrenergic receptor-mediated Ca2+ channel modulation.

Background: The superior hypogastric plexus (SHGP) carries afferents from the viscera of the lower abdomen and pelvis. Neurolytic block of this plexus is used for reducing pain resulting from malignancy in these organs. The ganglion impar (GI) innervats the perineum, distal rectum, anus, distal urethra, vulva, and distal third of the vagina. Different approaches to the ganglion impar neurolysis have been described in the literature., Objectives: To assess the feasibility, safety, and efficacy of combining the block of the SHGP through the postero-median transdiscal approach with the GI block by the trans-sacro-coccygeal approach for relief of pelvic and/or perineal pain caused by pelvic and/or perineal malignancies or any cancer related causes., Methods: Fifteen patients who had cancer-related pelvic pain, perineal pain, or both received a combined SHGP neurolytic block through the postero-median transdiscal approach using a 20-gauge Chiba needle and injection of 10 mL of 10% phenol in saline plus a GI neurolytic block by the trans-sacro-coccygeal approach using a 22-gauge 5 cm needle and injection of 4 - 6 mL of 8% phenol in saline. Pain intensity (measured using a visual analogue scale) and oral morphine consumption pre- and post-procedure were measured., Results: All patients presented with cancer-related pelvic, perineal, or pelviperineal pain. Pain scores were reduced from a mean (± SD) of 7.87 ± 1.19 pre-procedurally to 2.40 ± 2.10 one week post-procedurally (P < 0.05). In addition, the mean consumption of morphine (delivered via 30 mg sustained-release morphine tablets) was reduced from 98.00 ± 34.89 mg to 32.00 ± 28.48 mg after one week (P < 0.05). No complications or serious side effects were encountered during or after the block., Limitations: This study is limited by its small sample size and non-randomized study., Conclusion: A combined neurolytic SHGP block with GI block is an effective and safe technique for reducing pain in cancer patients presented with pelvic and/or perineal pain. Also, a combined SHGP block through a posteromedian transdiscal approach with a GI block through a trans-sacrococcygeal approach may be considered more effective and easier to perform than the recently invented bilateral inferior hypogastric plexus neurolysis through a transsacral approach.

Objective: This review examined the diagnostic approach, surgical treatment, and outcomes of cervical sympathetic chain schwannomas (CSCS) to guide clinical decision making., Data Sources: Medline, EMBASE, and Cochrane databases., Review Methods: A literature review from 1998 to 2013 identified 156 articles of which 51 representing 89 CSCS cases were evaluated in detail. Demographic, clinical, and outcomes data were extracted by 2 independent reviewers with high interrater reliability (κ = .79). Cases were mostly international (82%), predominantly from Asia (50%) and Europe (27%)., Conclusions: On average, patients were 42.6 years old (SD = 13.3) and had a neck mass ranging between 2 to 4 cm (52.7%) or >4 cm (43.2%). Nearly 70% of cases were asymptomatic at presentation. Presurgical diagnosis relied on CT (63.4%), MRI (59.8%), or both (19.5%), supplemented by cytology (33.7%), which was nearly always inconclusive (96.7%). US-treated cases were significantly more likely to receive presurgical MRI than internationally treated cases but less likely to have cytology (P < .05). Presurgical diagnosis was challenging, with only 11% confirmatory accuracy postsurgically. Irrespective of mass size, extracapsular resection (ie, complete resection with nerve sacrifice) was the most frequently (87.6%) performed surgical procedure. Common postsurgical adverse events included Horner's syndrome (91.1%), first bite syndrome (21.1%), or both (15.7%), with higher prevalence when mass size was >4 cm. Adverse events persisted in 82.3% of cases at an average 30.0 months (SD = 30.1) follow-up time., Implications for Practice: Given the typical CSCS patient is young and asymptomatic and the likelihood of persistent morbidity is high with standard surgical approaches, less invasive treatment options warrant consideration., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.)

Aberrant sympathetic sprouting is seen in the uninjured trigeminal ganglia of transgenic mice that ectopically express nerve growth factor under the control of the glial fibrillary acidic protein promoter. These sympathetic axons form perineuronal plexuses around a subset of sensory somata in 2- to 3-month-old transgenic mice. Here, we show that aged transgenic mice (i.e., 11-14 and 16-18 months old) have dystrophic sympathetic plexuses (i.e., increased densities of swollen axons), and that satellite glial cells, specifically those in contact with dystrophic plexuses in the aged mice display strong immunostaining for tumor necrosis factor alpha. The colocalization of dystrophic plexuses and reactive satellite glial cells in the aged mice coincides with degenerative features in the enveloped sensory somata. Collectively, these novel results show that, with advancing age, sympathetic plexuses undergo dystrophic changes that heighten satellite glial cell reactivity and that together these cellular events coincide with neuronal degeneration., (Copyright © 2014 Elsevier Inc. All rights reserved.)