The Relationship between the Ewing Test, Sudoscan Cardiovascular Autonomic Neuropathy Score and Cardiovascular Risk Score Calculated with SCORE2-Diabetes.

Background and Objectives: Cardiac autonomic neuropathy (CAN) is a severe complication of diabetes mellitus (DM) strongly linked to a nearly five-fold higher risk of cardiovascular mortality. Patients with Type 2 Diabetes Mellitus (T2DM) are a significant cohort in which these assessments have particular relevance to the increased cardiovascular risk inherent in the condition. Materials and Methods: This study aimed to explore the subtle correlation between the Ewing test, Sudoscan-cardiovascular autonomic neuropathy score, and cardiovascular risk calculated using SCORE 2 Diabetes in individuals with T2DM. The methodology involved detailed assessments including Sudoscan tests to evaluate sudomotor function and various cardiovascular reflex tests (CART). The cohort consisted of 211 patients diagnosed with T2DM with overweight or obesity without established ASCVD, aged between 40 to 69 years. Results: The prevalence of CAN in our group was 67.2%. In the study group, according SCORE2-Diabetes, four patients (1.9%) were classified with moderate cardiovascular risk, thirty-five (16.6%) with high risk, and one hundred seventy-two (81.5%) with very high cardiovascular risk. Conclusions: On multiple linear regression, the SCORE2-Diabetes algorithm remained significantly associated with Sudoscan CAN-score and Sudoscan Nephro-score and Ewing test score. Testing for the diagnosis of CAN in very high-risk patients should be performed because approximately 70% of them associate CAN. Increased cardiovascular risk is associated with sudomotor damage and that Sudoscan is an effective and non-invasive measure of identifying such risk.

Genetic markers of cardiac autonomic neuropathy in the Kazakh population.

BACKGROUND: Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that increases the risk of morbidity and mortality by disrupting cardiac innervation. Recent evidence suggests that CAN may manifest even before the onset of DM, with prediabetes and metabolic syndrome potentially serving as precursors. This study aims to identify genetic markers associated with CAN development in the Kazakh population by investigating the SNPs of specific genes. MATERIALS AND METHODS: A case-control study involved 82 patients with CAN (cases) and 100 patients without CAN (controls). A total of 182 individuals of Kazakh nationality were enrolled from a hospital affiliated with the RSE "Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan". 7 SNPs of genes FTO, PPARG, SNCA, XRCC1, FLACC1/CASP8 were studied. Statistical analysis was performed using Chi-square methods, calculation of odds ratios (OR) with 95% confidence intervals (CI), and logistic regression in SPSS 26.0. RESULTS: Among the SNCA gene polymorphisms, rs2737029 was significantly associated with CAN, almost doubling the risk of CAN (OR 2.03(1.09-3.77), p = 0.03). However, no statistically significant association with CAN was detected with the rs2736990 of the SNCA gene (OR 1.00 CI (0.63-1.59), p = 0.99). rs12149832 of the FTO gene increased the risk of CAN threefold (OR 3.22(1.04-9.95), p = 0.04), while rs1801282 of the PPARG gene and rs13016963 of the FLACC1 gene increased the risk twofold (OR 2.56(1.19-5.49), p = 0.02) and (OR 2.34(1.00-5.46), p = 0.05) respectively. rs1108775 and rs1799782 of the XRCC1 gene were associated with reduced chances of developing CAN both before and after adjustment (OR 0.24, CI (0.09-0.68), p = 0.007, and OR 0.43, CI (0.22-0.84), p = 0.02, respectively). CONCLUSION: The study suggests that rs2737029 (SNCA gene), rs12149832 (FTO gene), rs1801282 (PPARG gene), and rs13016963 (FLACC1 gene) may be predisposing factors for CAN development. Additionally, SNPs rs1108775 and rs1799782 (XRCC1 gene) may confer resistance to CAN. Only one polymorphism rs2736990 of the SNCA gene was not associated with CAN.

[Autoimmune Autonomic Ganglionopathy and Acute Autonomic Sensory Neuropathy].

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

Association between COVID-19 exposure and autonomic nervous system dysfunction in apparently healthy adults: an observational study.

OBJECTIVE: Coronavirus disease (COVID-19) is a respiratory disease caused by SARS-CoV-2, which complicates the functioning of multiple systems, including the autonomic nervous system (ANS), causing dysautonomia. Investigation of dysautonomia and its association with exposure to COVID-19 is limited in healthy people. Therefore, the study aimed to investigate the relationship between ANS dysautonomia and coronavirus exposure and compare the ANS function between exposed and non-exposed to COVID-19. SUBJECTS AND METHODS: The study involved 141 participants, with a mean age of 18-24.5 years, 83% male (49.6% exposed to COVID-19). The ANS was measured using a composite autonomic symptom scale (COMPASS-31) questionnaire and heart rate variability (HRV) using photoplethysmography. Exposure to COVID-19 was investigated using two national health-status tracking and COVID-19 exposure applications, "Sehhaty" and "Twakkalna". RESULTS: A significantly inverse weak correlation between COMPASS-31 scores and COVID-19 exposure (r=-0.2, p=0.04). No significant association was found between HRV and COVID-19 exposure. COMPASS-31 scores for the exposed group (median=15, n=70) were significantly higher than those for the non-exposed group (median=12, n=71), U=1,913.5, p=0.03. Height (r=-0.4, p=0.002) and gender (r=0.3, p=0.001) were moderately correlated with COMPASS-31 among the exposed group. CONCLUSIONS: These findings indicated that exposure to COVID-19 was associated with poorer ANS scores measured via COMPASS-31. Additionally, exposure to COVID-19 resulted in higher dysautonomia symptoms than non-exposed. Height and gender differences contribute to the severity of dysautonomia among exposed people.

Paroxysmal sympathetic hyperexcitability after brain injury: A clinical analysis of case series.

BACKGROUND: Paroxysmal sympathetic hyperexcitability (PSH) is a group of complex syndromes with various etiologies. Previous studies were limited to the description of traumatic brain injury (TBI), and the description of PSH after other types of brain injury was rare. We explored the clinical features, treatment, and prognosis of PSH after various types of brain injuries. METHODS: Patients admitted to the neurosurgery intensive care unit with PSH after brain injury from July 2019 to December 2022 were included. Demographic data, clinical manifestations, drug therapy, and disease prognosis were retrospectively collected and analyzed. RESULTS: Fifteen male and 9 female patients with PSH after brain injury were selected. TBI was most likely to cause PSH (66.7%), followed by spontaneous intracerebral hemorrhage (25%). Glasgow coma scale scores of 19 patients (79.2%) were lower than 8 and 14 patients (58.3%) underwent tracheotomy. Electroencephalogram monitoring was performed in 12 individuals, none of which showed epileptic waves. Clinical symptom scale showed mild symptoms in 17 cases (70.8%). Almost all patients were administered a combination of drugs. After follow-up, most patients had a poor prognosis and 2 (8.3%) died after discharge. CONCLUSION: The etiology of PSH is complex. TBI may be the most common cause of PSH. Non-TBI may also be an important cause of PSH. Therefore, early identification, prevention and diagnosis are helpful for determining the prognosis and outcome of the disease.

Autonomic Dysfunction from Diagnosis to Treatment.

Autonomic disorders can present with hypotension, gastrointestinal, genitourinary symptoms, and heat intolerance. Diabetes is the most common causes of autonomic failure, and management should focus on glucose control to prevent developing autonomic symptoms. The most prevalent cause of dysautonomia, or autonomic dysfunction, is Postural Orthostatic Tachycardia Syndrome (POTS). Autonomic testing characterizes causes for nonspecific symptoms but is not necessary in patients with classic presentations. Treatment for autonomic dysfunction and failure focus on discontinuing offending medications, behavioral modification, and pharmacologic therapy to decrease symptom severity. Autonomic failure has no cure; therefore, the focus remains on improving quality of life.

From Social Stress and Isolation to Autonomic Nervous System Dysregulation in Suicidal Behavior.

PURPOSE OF REVIEW: In this narrative review we wanted to describe the relationship of autonomic nervous system activity with social environment and suicidal spectrum behaviors. RECENT FINDINGS: Patients with suicidal ideation/suicide attempt have higher sympathetic nervous system (SNS) and lower parasympathetic nervous system (PNS) activity in resting conditions and during acute stress tasks compared with patients without suicidal ideation/suicide attempt. Death by suicide and violent suicide attempt also are related to SNS hyperactivation. Similarly, a SNS/PNS imbalance has been observed in people with childhood trauma, stressful life events or feelings of loneliness and isolation. Social support seems to increase PNS control and resilience. Due to the importance of the social context and stressful life events in suicidal behavior, SNS/PNS imbalance could act as a mediator in this relationship and be a source of relevant biomarkers. Childhood trauma and stressful life events may impair the autonomic nervous system response in suicidal patients. Loneliness, isolation and social support may act as moderators in acute stress situations.

Paroxysmal sympathetic hyperactivity during neurorehabilitation for severe acquired brain injury: current Scandinavian practice and Delphi consensus recommendations.

OBJECTIVES: To document current practice and develop consensus recommendations for the assessment and treatment of paroxysmal sympathetic hyperactivity (PSH) during rehabilitation after severe acquired brain injury. DESIGN: Delphi consensus process with three rounds, based on the Guidance on Conducting and REporting DElphi Studies (CREDES) guidelines, led by three convenors (the authors) with an expert panel. Round 1 was exploratory, with consensus defined before round 2 as agreement of at least 75% of the panel. SETTING: A working group within the Nordic Network for Neurorehabilitation. PANEL PARTICIPANTS: Twenty specialist physicians, from Sweden (9 participants), Norway (7) and Denmark (4), all working clinically with patients with severe acquired brain injury and with current involvement in clinical decisions regarding PSH. RESULTS: Consensus was reached for 21 statements on terminology, assessment and principles for pharmacological and non-pharmacological treatment, including some guidance on specific drugs. From these, an algorithm to support clinical decisions at all stages of inpatient rehabilitation was created. CONCLUSIONS: Considerable consensus exists in the Nordic countries regarding principles for PSH assessment and treatment. An interdisciplinary approach is needed. Improved documentation and collation of data on treatment given during routine clinical practice are needed as a basis for improving care until sufficiently robust research exists to guide treatment choices.

Long-COVID autonomic syndrome in working age and work ability impairment.

Long-COVID19 has been recently associated with long-sick leave and unemployment. The autonomic nervous system functioning may be also affected by SARS-CoV-2, leading to a chronic autonomic syndrome. This latter remains widely unrecognized in clinical practice. In the present study, we assessed the occurrence of Long-COVID19 Autonomic Syndrome in a group of active workers as well as the relationships between their autonomic dysfunction and work ability. This prospective observational study was conducted during the 2nd wave of the pandemic in Italy. Forty-five patients (53.6 ± 8.4 years; 32 M) hospitalized for COVID19, were consecutively enrolled at the time of their hospital discharge (T0) and followed-up for 6 months. Autonomic symptoms and work ability were assessed by COMPASS31 and Work Ability Index questionnaires at T0, one (T1), three and six (T6) months after hospital discharge and compared to those retrospectively collected for a period preceding SARS-CoV-2 infection. Clinical examination and standing test were also performed at T1 and T6. One in three working-age people developed a new autonomic syndrome that was still evident 6 months after the acute infection resolution. This was associated with a significant reduction in the work ability. Recognition of Long-COVID19 Autonomic Syndrome may promote early intervention to facilitate return to work and prevent unemployment.

Evaluation of cardiac autonomic dysfunctions in children with type 1 diabetes mellitus.

BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is a serious complication of diabetes, impacting the autonomic nerves that regulate the heart and blood vessels. Timely recognition and treatment of CAN are crucial in averting the onset of cardiovascular complications. Both clinically apparent autonomic neuropathy and subclinical autonomic neuropathy, particularly CAN pose a significant risk of morbidity and mortality in children with type 1 diabetes mellitus (T1DM). Notably, CAN can progress silently before manifesting clinically. In our study, we assessed patients with poor metabolic control, without symptoms, following the ISPAD 2022 guideline. The objective is is to determine which parameters we can use to diagnose CAN in the subclinical period. METHODS: Our study is a cross-sectional case-control study that includes 30 children diagnosed with T1DM exhibiting poor metabolic control (average HbA1c > 8.5% for at least 1 year) according to the ISPAD 2022 Consensus Guide. These patients, who are under the care of the pediatric diabetes clinic, underwent evaluation through four noninvasive autonomic tests: echocardiography, 24-h Holter ECG for heart rate variability (HRV), cardiopulmonary exercise test, and tilt table test. RESULTS: The average age of the patients was 13.73 ± 1.96 years, the average diabetes duration was 8 ± 3.66 years, and the 1-year average HbA1c value was 11.34 ± 21%. In our asymptomatic and poorly metabolically controlled patient group, we found a decrease in HRV values, the presence of postural hypotension with the tilt table test, and a decrease in ventricular diastolic functions that are consistent with the presence of CAN. Despite CAN, the systolic functions of the ventricles were preserved, and the dimensions of the cardiac chambers and cardiopulmonary exercise test were normal. CONCLUSIONS: CAN is a common complication of T1DM, often associated with the patient's age and poor glycemic control. HRV, active orthostatic tests, and the evaluation of diastolic dysfunctions play significant roles in the comprehensive assessment of CAN. These diagnostic measures are valuable tools in identifying autonomic dysfunction at an early stage, allowing for timely intervention and management to mitigate the impact of cardiovascular complications associated with T1DM.

Aerobic exercise attenuates dysautonomia, cardiac diastolic dysfunctions, and hemodynamic overload in female mice with atherosclerosis.

Cardiovascular risk increases during the aging process in women with atherosclerosis and exercise training is a strategy for management of cardiac risks in at-risk populations. Therefore, the aims of this study were to evaluate: (1) the influence of the aging process on cardiac function, hemodynamics, cardiovascular autonomic modulation, and baroreflex sensitivity in females with atherosclerosis at the onset of reproductive senescence; and (2) the impact of exercise training on age-related dysfunctions in this model. Eighteen Apolipoprotein-E knockout female mice were divided equally into young (Y), middle-aged (MA), and trained middle-aged (MAT). Echocardiographic exams were performed to verify cardiac morphology and function. Cannulation for direct recording of blood pressure and heart rate, and analysis of cardiovascular autonomic modulation, baroreflex sensitivity were performed. The MA had lower cardiac diastolic function (E'/A' ratio), and higher aortic thickness, heart rate and mean arterial pressure, lower heart rate variability and baroreflex sensitivity compared with Y. There were no differences between Y and MAT in these parameters. Positive correlation coefficients were found between aortic wall thickness with hemodynamics data. The aging process causes a series of deleterious effects such as hemodynamic overload and dysautonomia in female with atherosclerosis. Exercise training was effective in mitigating aged-related dysfunctions.

Serotonin syndrome treated with cyproheptadine using NPi from a digital pupillometer as a therapeutic indicator: A case report.

RATIONALE: Serotonin syndrome is a potentially life-threatening condition resulting from the use of antidepressants, their interactions with other serotonergic medications, or poisoning. It presents with a triad of psychiatric, dysautonomic, and neurological symptoms and is sometimes fatal. While cyproheptadine is a specific treatment option, the optimal duration of its administration remains unclear. The purpose of this report is to quantitatively assess the endpoints of serotonin syndrome treatment. Based on the hypothesis that neurological pupil index (NPi) on a digital pupil recorder would correlate with the severity of the serotonin syndrome, we administered cyproheptadine using NPi as an indicator. PATIENT CONCERNS: A patient with a history of depression was brought to our hospital after he overdosed on 251 tablets of serotonin and noradrenaline reuptake inhibitors. DIAGNOSES: On day 3, the patient was diagnosed with serotonin syndrome. INTERVENTIONS: Cyproheptadine syrup was administered at 4 mg every 4 hours. The NPi of the automated pupillometer was simultaneously measured. On day 5, the NPi exceeded 3.0 cyproheptadine was discontinued. OUTCOMES: The patient was discharged on day 7. LESSONS: The lack of considerable improvement during the treatment period suggests that the patient may have improved on his own. In this case, the relationship between NPi and the severity of serotonin syndrome could not be determined.

Impact of sleep quality and physical activity on blood pressure variability.

Increased blood pressure variability (BPV) is linked to cardiovascular disease and mortality, yet few modifiable BPV risk factors are known. We aimed to assess the relationship between sleep quality and activity level on longitudinal BPV in a cohort of community-dwelling adults (age ≥18) from 17 countries. Using Withings home measurement devices, we examined sleep quality and physical activity over one year, operationalized as mean daily step count and number of sleep interruptions, both transformed into tertiles. The primary study outcome was high BPV, defined as the top tertile of systolic blood pressure standard deviation. Our cohort comprised 29,375 individuals (mean age = 58.6 years) with 127.8±90.1 mean days of measurements. After adjusting for age, gender, country, body mass index, measurement days, mean blood pressure, and total time in bed, the odds ratio of having high BPV for those in the top tertile of sleep interruptions (poor sleep) was 1.37 (95% CI, 1.28-1.47) and 1.44 (95% CI, 1.35-1.54) for those in the lowest tertile of step count (physically inactive). Combining these exposures revealed a significant excess relative risk of 0.20 (95% CI, 0.04-0.35, p = 0.012), confirming their super-additive effect. Comparing individuals with the worst exposure status (lowest step count and highest sleep interruptions, n = 2,690) to those with the most optimal status (highest step count and lowest sleep interruptions, n = 3,531) yielded an odds ratio of 2.01 (95% CI, 1.80-2.25) for high BPV. Our findings demonstrate that poor sleep quality and physical inactivity are associated with increased BPV both independently and super-additively.

Sympathetic dysfunction as an early indicator of autonomic involvement in Parkinson's disease.

PURPOSE: The specific characteristics of autonomic involvement in patients with early Parkinson's disease (PD) are unclear. This study aimed to evaluate the characteristics of autonomic dysfunction in drug-naïve patients with early-stage PD without orthostatic hypotension (OH) by analyzing Valsalva maneuver (VM) parameters. METHODS: We retrospectively analyzed drug-naïve patients without orthostatic hypotension (n = 61) and controls (n = 20). The patients were subcategorized into early PD (n = 35) and mid-PD (n = 26) groups on the basis of the Hoehn and Yahr staging. VM parameters, including changes in systolic blood pressure at late phase 2 (∆SBPVM2), ∆HRVM3, Valsalva ratio (VR), pressure recovery time, adrenergic baroreflex sensitivity, and vagal baroreflex sensitivity, were assessed. RESULTS: In the early PD group, ∆SBPVM2, a marker of sympathetic function, was significantly lower compared with that in controls (risk ratio = 0.95, P = 0.027). Receiver operating characteristic (ROC) curve analysis showed an optimal cut-off value of -10 mmHg for ∆SBPVM2 [P = 0.002, area under the curve (AUC): 0.737]. VR exhibited an inverse relationship with Unified Parkinson's Disease Rating Scale Part 3 scores in the multivariable regression analysis (VR: P = 0.038, ß = -28.61), whereas age showed a positive relationship (age: P = 0.027, ß = 0.35). CONCLUSION: The ∆BPVM2 parameter of the VM may help detect autonomic nervous system involvement in early-PD without OH. Our results suggest that sympathetic dysfunction is an early manifestation of autonomic dysfunction in patients with PD.