Acute pandysautonomia-associated distal esophageal spasm is a rare disease with an unclear etiology. Here, we describe a 12-year-old boy with an acute pandysautonomia-associated distal esophageal spasm who was treated using a peroral endoscopic myotomy (POEM). The patient's clinical features included recurrent dysphagia, nausea, vomiting, growth retardation, and signs of autonomic nerve dysfunction (e.g., a decreased production of tears and sweat, and an increased production of saliva). Signs of the distal esophageal spasm were visible in upper gastrointestinal radiography, endoscopy, and high-resolution esophageal manometry. After the POEM, the patient exhibited improvements in nausea and vomiting, and his dysphagia symptoms were relieved by the 6-month follow-up visit. However, the patient's neurological problems persisted. The satisfactory short-term clinical responses in our patient suggest that POEM is feasible, safe, and effective for the treatment of acute pandysautonomia-associated distal esophageal spasms in children.

The post-acute sequelae of COVID-19 present major problems for many patients, their physicians and the health-care system. They are unrelated to the severity of the initial infection, are often highly symptomatic and can occur after vaccination. Many sequelae involve cardiovascular autonomic dysfunction, with postural orthostatic tachycardia syndrome in 30% of individuals. Prognosis is unknown, and treatment is still unsatisfactory.

In neurons, many membrane proteins, synthesized in cell bodies, must be efficiently delivered to axons to influence neuronal connectivity, synaptic communication, and repair. Previously, we found that axonal targeting of TrkA neurotrophin receptors in sympathetic neurons occurs via an atypical transport mechanism called transcytosis, which relies on TrkA interactions with PTP1B, a protein tyrosine phosphatase. Here, we generated TrkAR685A mice, where TrkA receptor signaling is preserved, but its PTP1B-dependent transcytosis is disrupted to show that this mode of axonal transport is essential for sympathetic neuron development and autonomic function. TrkAR685A mice have decreased axonal TrkA levels in vivo, loss of sympathetic neurons, and reduced innervation of targets. The neuron loss and diminished target innervation phenotypes are specifically restricted to the developmental period when sympathetic neurons are known to rely on the TrkA ligand, nerve growth factor, for trophic support. Postnatal TrkAR685A mice exhibit reduced pupil size and eyelid ptosis, indicative of sympathetic dysfunction. Furthermore, we also observed a significant loss of TrkA-expressing nociceptive neurons in the dorsal root ganglia during development in TrkAR685A mice, suggesting that transcytosis might be a general mechanism for axonal targeting of TrkA receptors. Together, these findings establish the necessity of transcytosis in supplying TrkA receptors to axons, specifically during development, and highlight the physiological relevance of this axon targeting mechanism in the nervous system.

The aim of this prospective study was to investigate autonomic function in Parkinson's disease with a multidimensional approach including clinical evaluation tools, head-up tilt test and morphological studies of the vagus nerve. Head-up tilt test parameters including high frequency power of the heart frequency interval, the ratio of low frequency power of the distance between two consecutive R waves in electrocardiogram (RR interval) to the high frequency and low frequency power of systolic blood pressure were used to evaluate parasympathetic, cardiac sympathetic and vasomotor sympathetic functions, respectively, in 80 patients with Parkinson's disease. We examined the cross-sectional area of the vagus nerves bilaterally using nerve ultrasound and compared mean values with a control group of healthy subjects (n = 40) as well as patients with chronic inflammatory demyelinating polyneuropathy (n = 76). The cross-sectional area of right/left vagus nerve of Parkinson's patients was significantly lower compared to the right/left vagus nerve of the control group and of chronic demyelinating polyneuropathy patients. Furthermore, the cross-sectional area of the right vagus nerve was significantly larger from the one of the left vagus nerve for all groups. Based on tilt test, 43 patients (disease duration 7 ± 5, age at evaluation 71 ± 9, Hoehn and Yahr score 2.8 ± 8) were diagnosed with autonomic dysfunction (orthostatic hypertension n = 11, chronotropic incompetence n = 31, postural orthostatic tachycardia syndrome n = 1). Patients with orthostatic hypotension showed significantly higher Unified Parkinson's Disease Rating Scale-III values than those with chronotropic incompetence. The cross-sectional area of the vagus nerve correlated inversely with heart rate in rest and supine position and positively with tilt test parameters representing parasympathetic modulation through vagal activity [high frequency power of the distance between two consecutive R waves in electrocardiogram (RR interval)] at rest. We demonstrate for the first time that morphological characteristics of the vagus nerve correlate with parameters of parasympathetic function from the spectral analysis of cardiovascular parameters in tilt test for Parkinson's patients. This correlation reveals the impact of the atrophy of vagal atrophy for autonomic function in Parkinson's disease. Nerve ultrasound of the vagus nerve could potentially be used as an adjunct to tilt table examination to diagnose autonomic dysfunction.

As one of the most frequent complications of diabetes, diabetic neuropathy often involves peripheral and central nervous systems. Neuroinflammation is the key pathogenic factor of secondary nerve injury in diabetes. NOD-like receptor pyrin domain-containing 3(NLRP3) inflammasome is a group of subcellular multiprotein complexes, including NLRP3, apoptosis associated speck-like protein(ASC), and pro-cysteinyl aspartate specific proteinase 1(pro-caspase-1). NLRP3 inflammasome is an inducer of innate immune responses. Its activation stimulates the inflammatory cascade reaction, promotes the release of inflammatory mediators, triggers cell death and uncontrolled autophagy, activates glial cells, facilitates peripheral immune cell infiltration, and initiates amyoid β(Aβ)-tau cascade reactions. As a result, it contributes to the central nerve, somatic nerve, autonomic nerve, and retinal nerve cell damage secondary to diabetes. Therefore, due to its key role in the neuroinflammation responses of the body, NLRP3 inflammasome may provide new targets for the treatment of diabetic neuropathy. With multi-target and low-toxicity advantages, traditional Chinese medicine plays a vital role in the treatment of diabetic neuropathy. Accumulating evidence has shown that traditional Chinese medicine exerts curative effects on diabetic neuropathy possibly through regulating NLRP3 inflammasome. Although the role of NLRP3 inflammasome in diabetes and related complications has been investigated in the literature, systematical studies on drugs and mechanism analysis for secondary neuropathy are still lacking. In this article, the role of NLRP3 inflammasome in diabetic neuropathy was explored, and the research progress on traditional Chinese medicine in the treatment of diabetic neuropathy through NLRP3 inflammasome was reviewed.

Patients who require antipsychotic drug treatment are at increased risk of fractures, including osteoporosis-related fragility fractures, for reasons related to demographics, illness-related factors, and treatment-related factors. As examples, patients with dementia may be vulnerable to falls due to cognitive and psychomotor impairment, patients with schizophrenia may be vulnerable to injury related to physical restlessness or physical aggression, and patients receiving antipsychotics may suffer falls related to sedation, psychomotor impairment, bradykinesia, or postural hypotension. Antipsychotics may also increase the risk of fracture through long-term hyperprolactinemia and resultant osteoporosis. A meta-analysis of 36 observational studies conducted in mostly elderly samples found that antipsychotic exposure was associated with an increased risk of hip fracture as well as increased risk of any fracture; the findings were consistent in almost all subgroup analyses. An observational study that controlled for confounding by indication and illness severity found that fragility fractures in patients with schizophrenia were associated with higher daily doses, higher cumulative doses, longer duration of treatment, and prolactin-raising rather than prolactin-sparing antipsychotics; in patients receiving prolactin-raising antipsychotics, the concurrent use of aripiprazole appeared protective. The absolute risks of fracture are unknown and could vary depending on patient age, patient sex, indication for antipsychotic use, nature of the antipsychotic (and associated risk of sedation, psychomotor impairment, bradykinesia, and postural hypotension), daily dose prescribed, duration of antipsychotic exposure, baseline risk of fracture, and other risk factors. Patients should therefore be individually evaluated for risk factors for falls and fractures related to sociodemographic, clinical, and treatment-related risk factors. Patients identified to be at risk should be advised about risk-mitigating strategies. If prolactin-raising antipsychotics are required in the long term, prolactin levels should be monitored and prolactin-lowering strategies should be considered. Osteoporosis should be investigated and managed, if identified, to prevent fragility fractures.

The use of ECPELLA in patients with severe lung disease may result in an unfavorable phenomenon of differential hypoxia. The simultaneous evaluation of three arterial blood samples from different arterial line (right radial artery, left radial artery, ECMO arterial line) in patients at risk of Harlequin syndrome (also called differential hypoxemia (DH)) can localize the "mixing cloud" along the aorta. Focusing the attention on the "mixing cloud" position instead of on isolated flows of Veno-Arterial Extracorporeal Membrane Oxygenation (VA ECMO) and Impella CP makes the decision making easier about how to modify MCSs flows according to the clinical context. Herein, we present two cases in which ECPELLA configuration was used to treat a cardiogenic shock condition and how the ECPELLA-induced hypoxia was managed.

We investigated the changes in the oxidative stress and cardiovascular disease risk biomarkers, including the activity of the cardiac autonomic nervous system, in older adults with prehypertension following Riceberry rice bran oil supplementation. A total of 35 women aged 60 to 76 years with prehypertension were randomly allocated to two groups, one of which was supplemented with rice bran oil (n=18) and the other with Riceberry rice bran oil (n=17) at 1,000 mg daily for 8 weeks. Prior to and after the supplementation, oxidative stress and cardiovascular risk biomarkers (primary outcomes), heart rate variability, and blood pressure (secondary outcomes) were investigated. Results showed that plasma malondialdehyde, blood glutathione disulfide, and tumor necrosis factor-alpha levels were significantly decreased, and the ratio of reduced glutathione to glutathione disulfide significantly increased in both groups after supplementation (all P<0.05). No significant differences were observed between groups. Heart rate variability and blood pressure did not statistically significantly change subsequent to supplementation in either group and did not differ between groups. In conclusion, Riceberry rice bran oil supplementation for 8 weeks alleviates oxidative stress and inflammation in older adults with prehypertension to a similar extent as rice bran oil supplementation.

Objective: To analyze the clinical characteristics and risk factors of malignant vasovagal syncope (VVS) in children. Methods: This was a case-control study. The data of 368 VVS patients who were treated in the Department of Cardiology, Children's Hospital, Capital Institute of Pediatrics from June 2017 to December 2021 was collected and analyzed. They were divided into malignant VVS group and non-malignant VVS group according to the presence of sinus arrest, and then their demographic characteristics were compared. The children with malignant VVS and complete clinical information were recruited into the case group and were matched by age and sex (1∶4 ratio) with non-malignant VVS patients during the same period.Their clinical characteristics and lab tests were compared. Independent sample t test, Mann Whitney U or χ2 test was used for comparison between groups.Logistic regression was used to analyze the risk factors for malignant VVS in children. Results: Eleven malignant VVS and 342 non-malignant VVS met the inclusion and exclusion critera. Eleven malignant VVS and 44 non-malignant children were recruited in the case-control study. Ten patients of the 11 malignant VVS had a cardiac arrest occurring at 35 (28, 35) minutes of the head-up tilt test, and the duration of sinus arrest was (9±5) s. One patient had syncope occurring while waiting for drawing blood, and the duration of sinus arrest was 3.4 s. The children with malignant vasovagal syncope were younger than non-malignant VVS patients (9 (7, 10) vs. 12 (10, 14) years old, P<0.05), and had higher mean corpuscular hemoglobin concentration (MCHC) and standard deviation of the mean cardiac cycle over 5-minute period within 24 hours ((347±9) vs. (340±8) g/L, (124±9) vs. (113±28) ms, both P<0.05). Logistic regression analysis showed that MCHC was an independent risk factor for malignant VVS in pediatric patients (OR=1.13, 95%CI 1.02-1.26, P=0.024). Conclusions: The onset age of malignant VVS was younger, with no other special clinical manifestations. MCHC was an independent risk factor for malignant VVS.

Microorganisms in human life play a huge role: in particular, those that coexist with the host organism, inhabiting the skin, upper respiratory tract, external genitalia and especially the digestive tract. The intestinal microbiota, including bacteriome, mycobiome and virome, not only takes part in the digestion process, but also provides the synthesis of a number of vitamins. The intestinal microbiome also serves as the basis for a system of extensive bidirectional neuroendocrine pathways that connect microbiota with various regions of the central nervous system, the hypothalamic-pituitary-adrenal system, and the peripheral parts of the autonomic nervous system. This system of connections has got the name of gut-brain axis and has attracted close attention of scientists over the past two decades, since a targeted impact on the intestinal flora is potentially capable of changing the nature of nervous system regulatory influences on the whole body. It is especially important to study patterns of functioning of the gut-brain axis in patients with the nervous system pathology, namely neurodegenerative and demyelinating diseases. Methods for their treatment continue to improve, and perhaps the correction of the gut microbiotic composition will serve as an additional therapeutic approach. The review article describes current views on the role of the intestinal microbiota, provides the latest data on the composition of bacteriome, mycobiome, and virome in patients with relapsing-remitting multiple sclerosis.

The novel SARS-CoV-2 emerged in 2019, and the global COVID-19 pandemic continues into 2022. It has been known that a subset of patients develops chronic, debilitating symptoms after otherwise complete recovery from acute infection of COVID-19. Multiple terms have been used to describe this constellation of symptoms, including long COVID, long-haul COVID, and post-acute sequelae of SARS-CoV-2 syndrome (PASC). PASC is broadly defined as a wide range of new, returning, or ongoing symptoms at least four weeks after infection. Those patients are often seen in emergency departments after acute COVID- 19 infection, but their symptoms are not adequately managed because the underlying pathophysiology of PASC is not well understood. Among patients with PASC, postural orthostatic tachycardic syndrome (POTS) has been increasingly recognized. POTS is one of the most common forms of autonomic dysfunction and defined by a sustained orthostatic tachycardia during active standing or head-up tilt test in the absence of orthostatic hypotension or other cardiopulmonary diseases. Because POTS is a treatable condition, it is important to recognize POTS among PASC patients. Herein, we reviewed the current literature on POTS and dysautonomia in PASC in order to better understand the overlap and distinction between these pathologies.

An acute bout of exercise typically leads to short term exercise induced hypoalgesia (EIH), but this response is more variable in many chronic pain populations, including knee osteoarthritis (OA) and fibromyalgia (FM). There is evidence of autonomic nervous system (ANS) dysfunction in some chronic pain populations that may contribute to impaired EIH, but this has not been investigated in people with knee OA. The aim of this study was to assess the acute effects of isometric exercise on the nociceptive and autonomic nervous systems in people with knee OA and FM, compared to pain-free controls.

Mechanistic studies suggested that excess sympathetic activity promotes arterial hypertension while worsening insulin sensitivity. Older patients with type 2 diabetes are at particularly high cardiovascular and metabolic risk. However, data on sympathetic activity in this population is scarce.

Spectral analysis of heart rate variability (HRV) is widely used as a non-invasive method to assess the cardiovascular autonomic function. Of the two main frequency components of HRV, namely low-frequency (LF, 0.04-0.15 Hz) and high-frequency (HF, 0.15-0.4 Hz) components, it is generally accepted that the HF power reflects modulation of heart rate which is mediated by cardiac parasympathetic (vagal) nerve activity. In contrast, the origin and functional correlates of the LF component are still controversial. Although several lines of evidence have indicated a close correlation between LF power and the baroreflex modulation of autonomic outflows, the detailed mechanisms underlying the genesis of the LF component remain unclarified. In this study, we conducted an ultra-short-term (UST) spectral analysis of R-R interval (RRI) time series using Fast Fourier Transform (FFT) with 5- and 25-s windows to clarify the temporal relationships among transient changes in the RRI and, LF and HF powers in healthy subjects. We found that during active standing, transient RRI increases occurred sporadically. The UST spectral analysis revealed that this RRI increase was associated with a simultaneous increase in HF power which was closely linked to the prominent LF power increase. These results indicate that during active standing, increases in LF and HF powers occur simultaneously, and they may reflect enhanced cardiac vagal activity which generates transient bradycardia.

Postural orthostatic tachycardia syndrome (POTS) affects 3 million in the US and 11 million globally. Signs and symptoms can vary and greatly impact a patient's quality of life. This article focuses on the prevalence, clinical manifestations, diagnosis, treatment, and patient education surrounding POTS.

Orthostatic hypotension is a frequent pathology especially in older adults and inhospital patients. Prevalence is increasing with age, and is about 30 % of patients older than 65 years. Orthostatic hypotension is defined as a fall in blood pressure of at least 20 mmHg systolic or 10 mmHg diastolic when standing or during head-up tilt testing. Orthostatic hypotension is significantly associated with several adverse outcomes such as falls, neurodegenerative disease, cardiovascular outcomes (such as stroke or heart failure), and mortality. Different mechanisms may be involved in pathogeny especially medications. Etiological work up will evaluate cardiac response when standing. Neurogenic orthostatic hypotension is characterized by a cardiovascular autonomic failure due to central or peripheral nervous system disorders. Non-neurogenic orthostatic hypotension is primarily caused by hypovolemia. Therapeutic management is based on non-pharmacological therapies, especially legs venous compression, even if evidence for effectiveness is lacking. Pharmacological therapies may be necessary for neurogenic orthostatic hypotension.

Autonomic imbalance is an important characteristic of patients after myocardial infarction (MI) and adversely contributes to post-MI cardiac remodeling and ventricular arrhythmias (VAs). A previous study proved that optogenetic modulation could precisely inhibit cardiac sympathetic hyperactivity and prevent acute ischemia-induced VAs. Here, a wireless self-powered optogenetic modulation system is introduced, which achieves long-term precise cardiac neuromodulation in ambulatory canines. The wireless self-powered optical system based on a triboelectric nanogenerator is powered by energy harvested from body motion and realized the effective optical illumination that is required for optogenetic neuromodulation (ON). It is further demonstrated that long-term ON significantly mitigates MI-induced sympathetic remodeling and hyperactivity, and improves a variety of clinically relevant outcomes such as improves ventricular dysfunction, reduces infarct size, increases electrophysiological stability, and reduces susceptibility to VAs. These novel insights suggest that wireless ON holds translational potential for the clinical treatment of arrhythmia and other cardiovascular diseases related to sympathetic hyperactivity. Moreover, this innovative self-powered optical system may provide an opportunity to develop implantable/wearable and self-controllable devices for long-term optogenetic therapy.

We present a case of an 82-year-old woman presenting with left-sided Horner's syndrome and stroke. She also had a 6-week history of intermittent dizziness, reduced appetite, lethargy, muscle stiffness and weight loss. Examination revealed left temporal artery and left posterior auricular artery tenderness. Her ESR showed 62 mm/hr and imaging showed left vertebral artery dissection. Temporal artery biopsy was positive.The case highlights a rare presentation of giant cell arteritis with Horner's syndrome and left vertebral artery dissection. High clinical suspicion is required to prevent delay in diagnosis and treatment.

The autonomic nervous system regulates pancreatic function. Islet capillaries are essential for the extension of axonal projections into islets, and both of these structures are important for appropriate islet hormone secretion. Because beta cells provide important paracrine cues for islet glucagon secretion and neurovascular development, we postulated that beta cell loss in type 1 diabetes (T1D) would lead to a decline in intra-islet capillaries and reduction of islet innervation, possibly contributing to abnormal glucagon secretion. To define morphological characteristics of capillaries and nerve fibers in islets and acinar tissue compartments, we analyzed neurovascular assembly across the largest cohort of T1D and normal individuals studied thus far. Because innervation has been studied extensively in rodent models of T1D, we also compared the neurovascular architecture between mouse and human pancreas and assembled transcriptomic profiles of molecules guiding islet angiogenesis and neuronal development. We found striking inter-species differences in islet neurovascular assembly but relatively modest differences at transcriptome level, suggesting post-transcriptional regulation may be involved in this process. To determine if islet neurovascular arrangement is altered following beta cell loss in T1D, we compared pancreatic tissues from non-diabetic, recent-onset T1D (<10 years duration), and longstanding T1D donors (>10 years duration). Both islets and acinar tissue had greater capillary density in recent-onset T1D accompanied by overall greater islet nerve fiber density in recent-onset and longstanding T1D as visualized by a pan-neuronal marker. We did not detect changes in sympathetic axons in either T1D cohort. Additionally, nerve fibers overlapped with extracellular matrix (ECM), supporting its role in the formation and function of axonal processes. These results indicate that pancreatic capillaries and nerve fibers persist in T1D despite beta cell loss, suggesting that alpha cell secretory changes may be decoupled from neurovascular components.