Risk factors and outcome of hyponatremia in patients with Guillain-Barré syndrome.

The objective of the present study was to evaluate the risk factors and outcomes associated with hyponatremia in patients with Guillain-Barré syndrome (GBS). We retrospectively studied 80 consecutive patients with GBS who visited our hospital and compared clinical, laboratory, and electrophysiological findings of patients with and without hyponatremia. Disability was evaluated using the Hughes grading system. Of the 80 patients, 18 (23%) had hyponatremia. Hyponatremia was significantly associated with older age (P = 0.003), urinary retention (P < 0.0001), Hughes grade ≥ 4 at admission and nadir (P = 0.003 and P < 0.001, respectively), acute inflammatory demyelinating polyneuropathy subtype (P = 0.017), sepsis (P = 0.001), mechanical ventilator support (P = 0.013), longer hospitalization length of stay (P < 0.0001), and inability to walk independently at 6 months (P < 0.001). Multivariate analysis performed to assess the risk factors of hyponatremia revealed that urinary retention (odds ratio [OR] 30.7, 95% confidence interval [CI] 3.6-264.4; P = 0.002) and mechanical ventilator support (OR 13.8, 95% CI 1.6-118.0; P = 0.017) were significant independent risk factors of hyponatremia. In assessing the outcomes of patients with hyponatremia, multivariate analysis showed that hyponatremia was independently associated with hospitalization length of stay ≥ 60 days and inability to walk independently at 6 month, with the former showing statistical significance but the latter not (OR 9.3, 95% CI 1.8-47.7; P = 0.007 and OR 4.9, 95% CI 0.9-26.3; P = 0.066, respectively). Therefore, we demonstrate that, along with mechanical ventilator support, urinary retention-possibly indicating autonomic dysfunction-is a risk factor of hyponatremia in GBS. Moreover, we confirm that hyponatremia is associated with poor outcome in GBS.

Altered connectivity of central autonomic network: effects of dysautonomia in hereditary transthyretin amyloidosis with polyneuropathy.

BACKGROUND: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a progressive fatal disorder caused by deposition of mutant transthyretin (TTR) amyloids mainly in the nerves and heart. Autonomic dysfunction is a major disabling manifestation, affecting 90% of patients with late-onset ATTRv-PN. The current study aimed to investigate brain functional alterations associated with dysautonomia due to peripheral autonomic nerve degeneration in ATTRv-PN. METHODS: Resting-state functional MRI data were acquired from 43 ATTRv-PN patients predominantly of A97S (p.A117S) genotype, and the functional connectivity of central autonomic regions was assessed. RESULTS: Compared with age-matched healthy controls, the ATTRv-PN patients exhibited (1) reduced functional connectivity of the central autonomic regions such as hypothalamus, amygdala, anterior insula, and middle cingulate cortex with brain areas of the limbic, frontal, and somatosensory systems, and (2) correlations of reduced functional autonomic connectivity with the severity of autonomic dysfunction especially orthostatic intolerance, decreased heart rate variability, and greater clinical disability. CONCLUSIONS: Our findings provide evidence linking peripheral autonomic dysfunction with altered connectivity in the central autonomic network in ATTRv-PN.

The effect of heart rate variability on the choroidal vascularity of the optical coherence tomography and angiography in central serous chorioretinopathy.

PURPOSE: To investigate the correlation between the autonomic nervous system and choroidal vascularity in patients with central serous chorioretinopathy (CSC), using heart rate variability (HRV) analysis, optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: We retrospectively analyzed data of 25 patients with unilateral CSC (50 eyes, including the unaffected fellow eyes) and 25 healthy controls. The assessment involved a 5-minute HRV analysis encompassing both frequency and time domains, especially low frequency (LF), high frequency (HF), and LF/HF ratio. In OCT (12 × 9 mm) and en-face OCTA (3 × 3 mm) scans, we measured parameters including choroidal vascularity index (CVI), choroidal vessel density in the middle and deep layers, and choriocapillaris flow void. Regression analysis was conducted to elucidate the associations between HRV parameters and OCT/OCTA measurements. RESULTS: Normalized LF(LFnorm) and LF/HF ratios were higher in patients with CSC than in healthy controls. LFnorm and the log-transformed ratio of LF to HF [log(LF/HF)] demonstrated a significant and borderline correlation with CVI in the linear regression analysis (P = 0.040, R2 = 0.171, and P = 0.059, R2 = 0.147, respectively). Both CVI and deep choroid vessel density showed a more significant association with LFnorm and log (LF/HF) in the non-linear quadratic regression analysis than in the linear analysis (all, P < 0.04, R2 > 0.25). CONCLUSION: The frequency-domain parameters of HRV, including LFnorm and log (LF/HF), demonstrated a significant association with indicators reflective of large choroidal vessel luminal area on macular OCT/OCTA scans. This observation implies complicated modulation of choroidal blood flow by the autonomic nervous system in CSC.

The Interplay of HIV and Long COVID in Sub-Saharan Africa: Mechanisms of Endothelial Dysfunction.

PURPOSE OF REVIEW: Long COVID affects approximately 5 million people in Africa. This disease is characterized by persistent symptoms or new onset of symptoms after an acute SARS-CoV-2 infection. Specifically, the most common symptoms include a range of cardiovascular problems such as chest pain, orthostatic intolerance, tachycardia, syncope, and uncontrolled hypertension. Importantly, these conditions appear to have endothelial dysfunction as the common denominator, which is often due to impaired nitric oxide (NO) mechanisms. This review discusses the role of mechanisms contributing to endothelial dysfunction in Long COVID, particularly in people living with HIV. RECENT FINDINGS: Recent studies have reported that increased inflammation and oxidative stress, frequently observed in Long COVID, may contribute to NO dysfunction, ultimately leading to decreased vascular reactivity. These mechanisms have also been reported in people living with HIV. In regions like Africa, where HIV infection is still a major public health challenge with a prevalence of approximately 26 million people in 2022. Specifically, endothelial dysfunction has been reported as a major mechanism that appears to contribute to cardiovascular diseases and the intersection with Long COVID mechanisms is of particular concern. Further, it is well established that this population is more likely to develop Long COVID following infection with SARS-CoV-2. Therefore, concomitant infection with SARS-CoV-2 may lead to accelerated cardiovascular disease. We outline the details of the worsening health problems caused by Long COVID, which exacerbate pre-existing conditions such as endothelial dysfunction. The overlapping mechanisms of HIV and SARS-CoV-2, particularly the prolonged inflammatory response and chronic hypoxia, may increase susceptibility to Long COVID. Addressing these overlapping health issues is critical as it provides clinical entry points for interventions that could improve and enhance outcomes and quality of life for those affected by both HIV and Long COVID in the region.

Combining blood pressure variability and heart rate variability to analyze the autonomic nervous function of rotenone induced Parkinson's rat model.

BACKGROUND: Parkinson's patients have significant autonomic dysfunction, early detect the disorder is a major challenge. To assess the autonomic function in the rat model of rotenone induced Parkinson's disease (PD), Blood pressure and ECG signal acquisition are very important. NEW METHOD: We used telemetry to record the electrocardiogram and blood pressure signals from awake rats, with linear and nonlinear analysis techniques calculate the heart rate variability (HRV) and blood pressure variability (BPV). we applied nonlinear analysis methods like sample entropy and detrended fluctuation analysis to analyze blood pressure signals. Particularly, this is the first attempt to apply nonlinear analysis to the blood pressure evaluate in rotenone induced PD model rat. RESULTS: HRV in the time and frequency domains indicated sympathetic-parasympathetic imbalance in PD model rats. Linear BPV analysis didn't reflect changes in vascular function and blood pressure regulation in PD model rats. Nonlinear analysis revealed differences in BPV, with lower sample entropy results and increased detrended fluctuation analysis results in the PD group rats. COMPARISON WITH EXISTING METHODS AND CONCLUSIONS: our experiments demonstrate the ability to evaluate autonomic dysfunction in models of Parkinson's disease by combining the analysis of BPV with HRV, consistent with autonomic impairment in PD patients. Nonlinear analysis by blood pressure signal may help in early detection of the PD. It indicates that the fluctuation of blood pressure in the rats in the rotenone model group tends to be regular and predictable, contributes to understand the PD pathophysiological mechanisms and to find strategies for early diagnosis.

Atomoxetine for Intradialytic Hypotension in a Patient on Hemodialysis: A Case Report.

Intradialytic hypotension significantly affects patient safety and clinical outcomes during hemodialysis. Despite various pharmacological and nonpharmacological interventions, effective management remains elusive. In this report, we detail a case of intradialytic hypotension in a male patient in his 40s, undergoing hemodialysis with a history of polycystic kidney disease. Eight years ago, the patient underwent bilateral nephrectomy because of a severe cystic infection, after which his systolic blood pressure (BP) persistently remained at 50-70 mm Hg during dialysis sessions. The initial treatment strategy for hypotension included fludrocortisone, midodrine, and prednisolone, leading to a slight temporary increase in BP, which subsequently declined. As the patient's condition deteriorated, the administration of norepinephrine or dopamine became necessary to sustain BP during dialysis. Given the patient's resistance to these treatments, a daily dose of 25 mg of atomoxetine was introduced. Following this treatment, there was a gradual improvement in the patient's vertigo, weakness, and BP. This case illustrates that low-dose atomoxetine can alleviate symptoms and elevate BP in patients experiencing severe intradialytic hypotension during hemodialysis.

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

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

Progressive encephalomyelitis with rigidity and myoclonus: a pediatric case report and literature review.

BACKGROUND: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare and life-threatening autoimmune disease of the central nervous system. So far, only ten cases of PERM have been reported in children worldwide, including the one in this study. CASE PRESENTATION: We report a case of an 11-year-old boy with PERM with an initial presentation of abdominal pain, skin itching, dysuria, urinary retention, truncal and limb rigidity, spasms of the trunk and limbs during sleep, deep and peripheral sensory disturbances, and dysphagia. A tissue-based assay using peripheral blood was positive, demonstrated by fluorescent staining of mouse cerebellar sections. He showed gradual and persistent clinical improvement after immunotherapy with intravenous immunoglobulin, steroids, plasmapheresis and rituximab. CONCLUSIONS: We summarized the diagnosis and treatment of a patient with PERM and performed a literature review of pediatric PERM to raise awareness among pediatric neurologists. A better comprehension of this disease is required to improve its early diagnosis, treatment, and prognosis.

Functional-Molecular Mechanisms of Sympathetic-Parasympathetic Dysfunction in PVC-Induced Cardiomyopathy Revealed by Dual Stressor PVC-Exercise Challenge.

BACKGROUND: The significance of autonomic dysfunction in premature ventricular contraction-induced cardiomyopathy (PVC-CM) remain unknown. OBJECTIVE: Utilizing a novel "dual stressor" provocative challenge combining exercise with premature ventricular contraction (PVCs), the authors characterized the functional and molecular mechanisms of cardiac autonomic (cardiac autonomic nervous system) remodeling in a PVC-CM animal model. METHODS: In 15 canines (8 experimental, 7 sham), we implanted pacemakers and neurotelemetry devices and subjected animals to 12 weeks of bigeminal PVCs to induce PVC-CM. Sympathetic nerve activity (SNA), vagal nerve activity (VNA), and heart rate were continuously recorded before, during, and after treadmill exercise challenge with and without PVCs, at baseline and after development of PVC-CM. Western blot and enzyme-linked immunosorbent assay were used to evaluate molecular markers of neural remodeling. RESULTS: Exercise triggered an increase in both SNA and VNA followed by late VNA withdrawal. With PVCs, the degree of exercise-induced SNA augmentation was magnified, whereas late VNA withdrawal became blunted. After PVC-CM development, SNA was increased at rest but failed to adequately augment during exercise, especially with PVCs, coupled with impaired VNA and heart rate recovery after exercise. In the remodeled cardiac autonomic nervous system, there was widespread sympathetic hyperinnervation and elevated transcardiac norepinephrine levels but unchanged parasympathetic innervation, indicating sympathetic overload. However, cardiac nerve growth factor was paradoxically downregulated, suggesting an antineurotrophic counteradaptive response to PVC-triggered sympathetic overload. CONCLUSIONS: Sympathetic overload, sympathetic dysfunction, and parasympathetic dysfunction in PVC-CM are unmasked by combined exercise and PVC challenge. Reduced cardiac neurotrophic factor might underlie the mechanisms of this dysfunction. Neuromodulation therapies to restore autonomic function could constitute a novel therapeutic approach for PVC-CM.

Impact of Concurrent Exercise Training on Cardiac Autonomic Modulation, Metabolic Profile, Body Composition, Cardiorespiratory Fitness, and Quality of Life in Type 2 Diabetes with Cardiac Autonomic Neuropathy: A Randomized Controlled Trial.

Background: Type 2 diabetes mellitus (T2DM) often leads to cardiac autonomic neuropathy (CAN), a severe complication affecting cardiovascular health. Exercise training is a proven intervention for improving metabolic control and cardiovascular health in T2DM, but the effects of concurrent exercise training (CET), combining aerobic and resistance exercises, on CAN are not fully understood. Objective: This randomized controlled trial investigates the impact of a structured CET program on cardiac autonomic modulation, metabolic profile, body composition, cardiorespiratory fitness (CRF), and quality of life (QoL) in individuals with T2DM and CAN. Methods: A total of 96 participants, aged 35-70 years, with T2DM and CAN, were randomized into CET (n = 48) and control (n = 48) groups. The CET group engaged in combined aerobic and resistance training three times per week for 13 weeks, while the control group received standard care. Primary outcomes included heart rate variability (HRV) and heart rate recovery (HRR). Secondary outcomes were metabolic profile, body composition, CRF, and QoL, which were assessed using standardized protocols and validated questionnaires. The trial was registered with the Clinical Trials Registry-India (CTRI/2021/09/036711). Results: Significant improvements were noted in the CET group compared to controls. HRV metrics (SDNN, RMSSD, pNN50, TP, LF power, HF power, and LF/HF ratio) and HRR metrics (HRR30s, HRR1, HRR2, and HRR3) all showed significant enhancements (p < 0.01). The CET group also exhibited substantial reductions in fasting blood glucose, postprandial blood glucose, HbA1c, waist circumference, hip circumference, and percentage body fat (p < 0.01). Improvements were observed in lipid profile markers and CRF (VO2max) (p < 0.01). QoL scores improved significantly in the CET group as per the ADDQoL-19 (p < 0.01). Conclusions: CET significantly enhances cardiac autonomic modulation, metabolic profile, body composition, CRF, and QoL in individuals with T2DM and CAN. These findings support the integration of CET into standard T2DM management to improve clinical outcomes and QoL. Further research is needed to explore the long-term benefits and broader applicability of CET in diverse diabetic populations.

Cardiopulmonary and metabolic responses during a 2-day CPET in myalgic encephalomyelitis/chronic fatigue syndrome: translating reduced oxygen consumption to impairment status to treatment considerations.

BACKGROUND: Post-exertional malaise (PEM), the hallmark symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), represents a constellation of abnormal responses to physical, cognitive, and/or emotional exertion including profound fatigue, cognitive dysfunction, and exertion intolerance, among numerous other maladies. Two sequential cardiopulmonary exercise tests (2-d CPET) provide objective evidence of abnormal responses to exertion in ME/CFS but validated only in studies with small sample sizes. Further, translation of results to impairment status and approaches to symptom reduction are lacking. METHODS: Participants with ME/CFS (Canadian Criteria; n = 84) and sedentary controls (CTL; n = 71) completed two CPETs on a cycle ergometer separated by 24 h. Two-way repeated measures ANOVA compared CPET measures at rest, ventilatory/anaerobic threshold (VAT), and peak effort between phenotypes and CPETs. Intraclass correlations described stability of CPET measures across tests, and relevant objective CPET data indicated impairment status. A subset of case-control pairs (n = 55) matched for aerobic capacity, age, and sex, were also analyzed. RESULTS: Unlike CTL, ME/CFS failed to reproduce CPET-1 measures during CPET-2 with significant declines at peak exertion in work, exercise time, V ˙ e, V ˙ O2, V ˙ CO2, V ˙ T, HR, O2pulse, DBP, and RPP. Likewise, CPET-2 declines were observed at VAT for V ˙ e/ V ˙ CO2, PetCO2, O2pulse, work, V ˙ O2 and SBP. Perception of effort (RPE) exceeded maximum effort criteria for ME/CFS and CTL on both CPETs. Results were similar in matched pairs. Intraclass correlations revealed greater stability in CPET variables across test days in CTL compared to ME/CFS owing to CPET-2 declines in ME/CFS. Lastly, CPET-2 data signaled more severe impairment status for ME/CFS compared to CPET-1. CONCLUSIONS: Presently, this is the largest 2-d CPET study of ME/CFS to substantiate impaired recovery in ME/CFS following an exertional stressor. Abnormal post-exertional CPET responses persisted compared to CTL matched for aerobic capacity, indicating that fitness level does not predispose to exertion intolerance in ME/CFS. Moreover, contributions to exertion intolerance in ME/CFS by disrupted cardiac, pulmonary, and metabolic factors implicates autonomic nervous system dysregulation of blood flow and oxygen delivery for energy metabolism. The observable declines in post-exertional energy metabolism translate notably to a worsening of impairment status. Treatment considerations to address tangible reductions in physiological function are proffered. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, retrospectively registered, ID# NCT04026425, date of registration: 2019-07-17.

BODY AWARENESS, STRESS AND SYMPTOMS IN AUTONOMIC DYSFUNCTION IN PATIENTS WITH CHRONIC PAIN: AN EXPLORATIVE STUDY.

Objective: To assess pain outcomes, stress levels and body awareness among patients with chronic pain and explore potential associations between these variables. Design: An explorative study. Methods: Patients with chronic pain in primary and specialist care were assessed regarding pain intensity using the Numerical Rating Scale (NRS; 0-10 point scale) and stress levels using the Stress and Crisis Inventory (SCI-93; 0-140). To assess body awareness, multidimensional assessment of interoceptive awareness (MAIA; 0-5), a widely used self-report measure of interoceptive bodily awareness was used. Results: Participants (n = 42) reported an average NRS of 4.4, elevated stress levels and low body awareness. Stress levels were moderately correlated with pain intensity (r = 0.53; p < 0.001; 95% confidence interval [CI] 0.25-0.72) and number of pain sites (r = 0.58; p < 0.001; 95% CI 0.32-0.76). The regression analysis showed that pain outcomes predicted stress level scores and explained almost 50% of variance (R 2 = 0.47, p < 0.001). Moreover, shorter pain duration predicted a higher body awareness (p = 0.04). Conclusion: In patients with chronic pain, high pain intensity and multiple painful sites seem to be associated with impaired stress regulation. The patients had low body awareness, which was negatively influenced by pain duration.

A Novel Ultrasound-Guided Bilateral Vagal Nerve Hydrodissection With 5% Dextrose Without Local Anesthetic for Recalcitrant Chronic Multisite Pain and Autonomic Dysfunction.

Chronic pain is a complex condition that often poses diagnostic and management challenges due to its multifactorial etiology. This case report describes a 49-year-old pastor who presented with a three-year history of chronic pain affecting multiple sites, including the neck, bilateral shoulders, thoracic region, lower back, and bilateral knees. Additionally, he experienced shortness of breath on mild exertion, which adversely affected his ability to converse and speak publicly. The patient had a rapid resting heart rate of 100-120 beats per minute, occasional palpitations, and a 24-hour electrocardiogram that confirmed 15% premature ventricular complexes with bigeminy and trigeminy. He complained of limited appetite with early satiety, intermittent nausea, and regurgitation. Despite consultations with multiple specialists, no underlying causes were identified in the cardiac, respiratory, gastrointestinal, or psychological domains. Ultrasound-guided bilateral vagus nerve hydrodissection using 5% dextrose without local anesthetics was administered three times at monthly intervals, resulting in remarkable pain relief within three months and the effects persisted at the nine-month follow-up. Tachycardia was no longer perceived, resting heart rate slowed to 70-80 beats per minute, shortness of breath improved, and public speaking ability was restored. The patient's early satiety, nausea, and reflux complaints were resolved. This case report highlights the potential effectiveness of this novel intervention for chronic pain. Further research is warranted to validate these findings and explore the mechanism of action.

Hypothyroidism and Heart Rate Variability: Implications for Cardiac Autonomic Regulation.

Thyroid hormones have a pivotal role in controlling metabolic processes, cardiovascular function, and autonomic nervous system activity. Hypothyroidism, a prevalent endocrine illness marked by inadequate production of thyroid hormone, has been linked to different cardiovascular abnormalities, including alterations in heart rate variability (HRV). The study included 110 patients with hypothyroid disorder. Participants underwent clinical assessments, including thyroid function tests and HRV analysis. HRV, a measure of the variation in time intervals between heartbeats, serves as an indicator of autonomic nervous system activity and cardiovascular health. The HRV values were acquired using continuous 24-h electrocardiogram (ECG) monitoring in individuals with hypothyroidism, as well as after a treatment period of 3 months. All patients exhibited cardiovascular symptoms like palpitations or fatigue but showed no discernible cardiac pathology or other conditions associated with cardiac disease. The findings of our study demonstrate associations between hypothyroidism and alterations in heart rate variability (HRV) parameters. These results illustrate the possible influence of thyroid dysfunction on the regulation of cardiac autonomic function.

Decreased heart rate variability in sympathetic dominant states in Parkinson's disease and isolated REM sleep behavior disorder.

INTRODUCTION: Parkinson's disease (PD) presents with decreased heart rate variability (HRV) from its early stages. However, most of its evidence originates from HRV measurements in parasympathetic dominant states. In this study, we aimed to examine whether HRV in sympathetic dominant states during the head-up tilt table test (HUT) serves as a marker of autonomic dysfunction in PD and isolated REM sleep behavior disorder (iRBD). METHODS: We retrospectively assessed 102 patients with PD, 10 patients with iRBD, and 43 healthy controls. We then measured the coefficient of variation of RR intervals as an HRV parameter in sympathetic dominant states (CVRR-S) and parasympathetic dominant states (CVRR-P). Furthermore, we evaluated parameters of cardiac autonomic function, including HUT and the heart-to-mediastinum (H/M) ratio of cardiac metaiodobenzylguanidine scintigraphy. RESULTS: Patients with iRBD and PD at Hoehn and Yahr stage I exhibited a significantly decreased CVRR-S compared to healthy controls (controls vs. iRBD vs. PD; 1.82 ± 0.64 % vs. 1.13 ± 0.41 % vs. 1.15 ± 0.51 %, p < 0.001), although no further deterioration was observed in PD at more severe Hoehn and Yahr stages. CVRR-S showed a significant correlation with the H/M ratio in PD (r = 0.51, p < 0.001). Additionally, receiver operating characteristic (ROC) analysis revealed a larger area under the ROC curve in CVRR-S compared to that in CVRR-P for discriminating PD or iRBD from healthy controls. CONCLUSION: HRV in sympathetic dominant states shows the potential to be a marker of autonomic dysfunction in iRBD and early-stage PD, aiding in early diagnosis and patient stratification.

Mechanisms of complex regional pain syndrome.

Complex Regional Pain Syndrome (CRPS) is a chronic pain disorder characterized by a diverse array of symptoms, including pain that is disproportionate to the initial triggering event, accompanied by autonomic, sensory, motor, and sudomotor disturbances. The primary pathology of both types of CRPS (Type I, also known as reflex sympathetic dystrophy, RSD; Type II, also known as causalgia) is featured by allodynia, edema, changes in skin color and temperature, and dystrophy, predominantly affecting extremities. Recent studies started to unravel the complex pathogenic mechanisms of CRPS, particularly from an autoimmune and neuroimmune interaction perspective. CRPS is now recognized as a systemic disease that stems from a complex interplay of inflammatory, immunologic, neurogenic, genetic, and psychologic factors. The relative contributions of these factors may vary among patients and even within a single patient over time. Key mechanisms underlying clinical manifestations include peripheral and central sensitization, sympathetic dysregulation, and alterations in somatosensory processing. Enhanced understanding of the mechanisms of CRPS is crucial for the development of effective therapeutic interventions. While our mechanistic understanding of CRPS remains incomplete, this article updates recent research advancements and sheds light on the etiology, pathogenesis, and molecular underpinnings of CRPS.

Sympathetic Overactivity and Parasympathetic Impairment in Type 2 Diabetes: An Analysis of Cardiovascular Autonomic Functions.

Background Cardiovascular autonomic dysregulation is a known complication of Type 2 diabetes mellitus (T2DM), characterized by dysregulation in heart rate (HR) and blood pressure (BP). These disruptions in cardiovascular autonomic control can significantly influence the morbidity and mortality associated with the disease. Objectives This study aims to investigate how T2DM affects cardiovascular autonomic functions by comparing responses in HR, BP, and specific autonomic function tests between a control group without diabetes and a study group with diabetes. The research questions focus on assessing HR variability, baroreflex sensitivity, and other autonomic parameters to determine the extent of cardiovascular autonomic dysregulation in diabetic patients.  Methods This cross-sectional study involved 200 adults, divided equally between a control group (n = 100) and a T2DM study group (n = 100). The exclusion criteria included cardiovascular diseases and renal impairment. Data collection involved assessing baseline characteristics such as age and BMI. Cardiovascular measures, including HR, systolic blood pressure (SBP), and diastolic blood pressure (DBP), were recorded after a five-minute rest. Autonomic function tests assessed sympathetic and parasympathetic responses, including the cold pressor test and the isometric hand grip exercise test. The statistical analysis was conducted using IBM SPSS Statistics for Windows, Version 25 (Released 2017; IBM Corp., Armonk, New York, United States), focusing on independent t-tests to compare between groups, considering p-values <0.05 as significant. Potential confounding variables like age and BMI were accounted for in the analysis to ensure robust findings  Results The study group showed a higher average BMI (28.95 ± 5.60) compared to the control group (26.50 ± 5.70) and an increased resting HR (74.20 ± 8.60 bpm vs. 69.30 ± 9.10 bpm). The SBP was slightly higher in the study group (115.00 ± 19.00 mmHg vs. 114.50 ± 8.90 mmHg), while the DBP was lower (71.50 ± 10.70 mmHg vs. 72.80 ± 6.70 mmHg). The autonomic function tests showed a smaller increase in SBP (106.80 ± 11.00 mmHg) and a larger increase in DBP (75.90 ± 8.30 mmHg) upon standing in the study group compared to controls. The cold pressor test indicated increased sympathetic activity in the study group, with significant rises in SBP (133.70 ± 10.30 mmHg) and DBP (83.40 ± 9.00 mmHg) compared to the control group (SBP: 114.31 ± 11.87 mmHg, DBP: 71.85 ± 8.67 mmHg). These findings demonstrate marked differences in cardiovascular autonomic responses between the groups. Conclusions This study demonstrates that T2DM significantly impacts cardiovascular autonomic functions, with diabetic patients showing altered HR and BP indicative of increased sympathetic and decreased parasympathetic activity. These autonomic dysfunctions may heighten cardiovascular risk in diabetic individuals. Our findings highlight the importance of monitoring and managing cardiovascular autonomic functions in diabetic patients to reduce their risk of cardiovascular complications. Further research should investigate the underlying mechanisms and the effectiveness of interventions to improve autonomic function in this population.

Cardiovascular Autonomic Dysfunction in Hospitalized Patients with a Bacterial Infection: A Longitudinal Observational Pilot Study in the UK.

PURPOSE: A temporal reduction in the cardiovascular autonomic responses predisposes patients to cardiovascular instability after a viral infection and therefore increases the risk of associated complications. These findings have not been replicated in a bacterial infection. This pilot study will explore the prevalence of cardiovascular autonomic dysfunction (CAD) in hospitalized patients with a bacterial infection. METHODS: A longitudinal observational pilot study was conducted. Fifty participants were included: 13 and 37 participants in the infection group and healthy group, respectively. Recruitment and data collection were carried out during a two-year period. Participants were followed up for 6 weeks: all participants' cardiovascular function was assessed at baseline (week 1) and reassessed subsequently at week 6 so that the progression of the autonomic function could be evaluated over that period of time. The collected data were thereafter analyzed using STATA/SE version 16.1 (StataCorp). The Fisher Exact test, McNemar exact test, Mann-Whitney test and Wilcoxon test were used for data analysis. RESULTS: 32.4% of the participants in the healthy group were males (n = 12) and 67.6% were females (n = 25). Participants' age ranged from 33 years old to 76 years old with the majority being 40-60 years of age (62.1%) (Mean age 52.4 SD = 11.4). Heart rate variability (HRV) in response to Valsalva Maneuver, metronome breathing, standing and sustained handgrip in the infection group was lower than in the healthy group throughout the weeks. Moreover, both the HRV in response to metronome breathing and standing up showed a statistically significant difference when the mean values were compared between both groups in week 1 (p = 0.03 and p = 0.013). The prevalence of CAD was significantly higher in the infection group compared to healthy volunteers, both at the beginning of the study (p = 0.018) and at the end of follow up (p = 0.057), when all patients had been discharged. CONCLUSIONS: CAD, as assessed by the HRV, is a common finding during the recovery period of a bacterial infection, even after 6 weeks post-hospital admission. This may increase the risk of complications and cardiovascular instability. It may therefore be of value to conduct a wider scale study to further evaluate this aspect so recommendations can be made for the cardiovascular autonomic assessment of patients while they are recovering from a bacterial infectious process.

Chronic pain - A maladaptive compensation to unbalanced hierarchical predictive processing.

The ability to perceive pain presents an interesting evolutionary advantage to adapt to an ever-changing environment. However, in the case of chronic pain (CP), pain perception hinders the capacity of the system to adapt to changing sensory environments. Similar to other chronic perceptual disorders, CP is also proposed to be a maladaptive compensation to aberrant sensory predictive processing. The local-global oddball paradigm relies on learning hierarchical rules and processing environmental irregularities at a local and global level. Prediction errors (PE) between actual and predicted input typically trigger an update of the forward model to limit the probability of encountering future PEs. It has been hypothesised that CP hinders forward model updating, reflected in increased local deviance and decreased global deviance. In the present study, we used the local-global paradigm to examine how CP influences hierarchical learning relative to healthy controls. As hypothesised, we observed that deviance in the stimulus characteristics evoked heightened local deviance and decreased global deviance of the stimulus-driven PE. This is also accompanied by respective changes in theta phase locking that is correlated with the subjective pain perception. Changes in the global deviant in the stimulus-driven-PE could also be explained by dampened attention-related responses. Changing the context of the auditory stimulus did not however show a difference in the context-driven PE. These findings suggest that CP is accompanied by maladaptive forward model updating where the constant presence of pain perception disrupts local deviance in non-nociceptive domains. Furthermore, we hypothesise that the auditory-processing based biomarker identified here could be a marker of domain-general dysfunction that could be confirmed by future research.