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Background: Cardiovascular autonomic neuropathy (CAN) is known to affect patients with diabetes mellitus (DM) and cause adverse renal outcomes. We aimed to analyze the association between CAN and diabetic kidney disease (DKD)., Method: We enrolled 254 DM patients (mean age, 56.7 ± 15.2 years; male: female ratio, 1.17:1) with 19 (7.5%) type 1 DM patients and 235 (92.5%) type 2 DM patients. All patients had undergone cardiovascular autonomic function tests between January 2019 and December 2021 in a tertiary hospital in Korea. Cardiovascular autonomic neuropathy was categorized as normal, early, or definite after measuring three heart rate variability parameters. Diabetic kidney disease refers to a persistently elevated urinary albumin-creatinine ratio (uACR ≥30 mg/g) or reduced estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m 2 ). Logistic and Cox regression analyses were performed., Results: Patients with elevated uACR (n=107) and reduced eGFR (n=32) had a higher rate of definite CAN. After adjusting for covariates, definite CAN was associated with elevated uACR (OR=2.4, 95% CI 1.07-5.36) but not with reduced eGFR (OR=3.43, 95% CI 0.62-18.90). A total of 94 patients repeated uACR measurements within 2 years (mean follow-up, 586.3 ± 116.8 days). Both definite and early CAN were independent risk factors for elevated uACR (HR=8.61 and 8.35, respectively; both p <0.05). In addition, high-density lipoprotein cholesterol, ACE inhibitors/angiotensin receptor blockers and glucagon-like peptide-1 receptor agonists were independent protective factors for elevated uACR (HR=0.96, 0.25, and 0.07, respectively; all p <0.05)., Conclusion: Cardiovascular autonomic neuropathy is a potential indicator of DKD. Comprehensive management of DKD in the early stages of CAN may prevent microalbuminuria., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cho, Lim, Kwon, Chung, Moon, Yoon and Won.)

This systematic review aimed to explore the relationship between diabetic peripheral neuropathy (DPN) and cardiac autonomic neuropathy (CAN) in individuals with type 1 and 2 diabetes mellitus (DM)., Methods: The systematic review follow the protocol registered in Prospero (CRD42020182899). Two authors independently searched the PubMed, Scopus, Embase, Cochrane, and Web of Science databases. Discrepancies were resolved by a third author. The review included observational studies investigating the relationship between CAN and DPN in individuals with DM., Results: Initially, out of 1165 studies, only 16 were selected, with 42.8 % involving volunteers with one type of diabetes, 14.3 % with both types of diabetes and 14.3 % not specify the type. The total number of volunteers was 2582, mostly with type 2 DM. It was analyzed that there is a relationship between CAN and DPN. It was observed that more severe levels of DPN are associated with worse outcomes in autonomic tests. Some studies suggested that the techniques for evaluating DPN might serve as risk factors for CAN., Conclusion: The review presents a possible relationship between DPN and CAN, such as in their severity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Vinicius Saura Cardoso reports financial support was provided by Foundation for Research Support of Piauí State. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The harlequin syndrome is a rare disorder of the autonomic nervous system characterized by unilateral diminished flushing and sweating of the face following exposure to heat or physical activity. It results from sympathetic dysfunction and most commonly occurs idiopathically. A secondary development due to an underlying pathology (e.g., carotid artery dissection, tumors) must be excluded at first appearance. There is evidence that the cranial autonomic system is involved in the pathophysiology of trigeminal autonomic headaches like hemicrania continua. Therefore, an overlap in the pathophysiology of harlequin syndrome and trigeminal autonomic headache disorders seems plausible. However, the association of a harlequin syndrome with hemicrania continua was never reported., Case Presentation: This work describes the case of a 42-year-old female patient presenting to our headache unit. The patient reported persisting unilateral headache of the right side of dragging or squeezing character accompanied by trigeminal autonomic symptoms, including lacrimation, nasal congestion, conjunctival injection and Horner's syndrome, and was responsive to treatment with 75mg/d indomethacin. Five months after the initial consultation, the patient noted that the upper right quadrant of her face was pale after jogging. A harlequin syndrome was diagnosed. Further, she developed a short-lasting, bilateral headache of pulsatile character during strenuous exercise consistent with exertional headache. Comprehensive diagnostic evaluations, encompassing cranial and cervical MRI scans, laboratory tests, and biopsies, culminated in the diagnosis of Sjögren's syndrome. This finding suggests that the trigemino-autonomic dysfunction may either be idiopathic or a direct manifestation of Sjögren's syndrome., Conclusions: This report documents the case of a rare combination of a headache resembling probable hemicrania continua and the harlequin syndrome (and even exertional headache). It illustrates the underlying anatomy of the autonomic nervous system in a clinical context and emphasizes the hypothesis of a pathophysiological link between abnormal sympathetic activity and trigeminal autonomic headaches., (© 2024. The Author(s).)

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.

Objective: We investigated associations between gastrointestinal symptoms - evaluated as a combined weighted symptom score (CWSS) - Diabetic autonomic neuropathy (DAN), and distal symmetrical polyneuropathy (DSPN) in type 1 and type 2 diabetes., Research Design and Methods: Cross-sectional study in a tertiary outpatient clinic. CWSS was calculated based on questionnaires: gastroparesis composite symptom index (GCSI) and gastrointestinal symptom rating score (GSRS). DAN and DSPN were addressed using the composite autonomic symptom score 31 (COMPASS-31) questionnaire, cardiac autonomic reflex tests (CARTs), electrochemical skin conductance (ESC), vibration perception threshold (VPT), Michigan Neuropathy Screening Instrument (MNSI), pain- and thermal sensation. Analyses were adjusted for age, sex, diabetes duration, smoking, LDL-cholesterol, HbA 1C and systolic blood pressure. Type 1 and type 2 diabetes were evaluated separately., Results: We included 566 with type 1 diabetes and 377 with type 2 diabetes. Mean ± SD age was 58 ± 15 years and 565 (59.9 %) were women. A high CWSS was present in 143 (25 %) with type 1 and 142 (38 %) with type 2 diabetes. The odds of DAN by COMPASS-31 (p < 0.001) were higher in the high score group. For type 1 diabetes, odds of cardiac autonomic neuropathy were higher in the high CWSS group. The odds of DSPN by VPT and MNSI in type 1 diabetes, and by ESC, VPT and pain sensation in type 2 diabetes were higher in the high CWSS group., Conclusions: A high symptom score was associated with neuropathy by COMPASS-31 and vibration perception. Gastrointestinal symptom burden associated inconsistently with other neuropathy tests between diabetes types., Competing Interests: Declaration of competing interest No disclosures., (Copyright © 2024. Published by Elsevier Inc.)

Background: Autonomic dysfunction is prevalent in Parkinson's disease (PD) and can worsen quality of life. We examined: (a) whether specific autonomic symptoms were more strongly associated with anxiety or depression in PD and (b) whether overall autonomic dysfunction predicted mood trajectories over a 5-year period., Methods: Newly diagnosed individuals with PD ( N = 414) from the Parkinson's Progression Markers Initiative completed self-report measures of depression, anxiety, and autonomic symptoms annually. Cross-sectional linear regressions examined relationships between specific autonomic subdomains (gastrointestinal, cardiovascular, thermoregulatory, etc.) and mood. Multilevel modeling examined longitudinal relationships with total autonomic load., Results: Gastrointestinal symptoms were associated with both higher anxiety ( b = 1.04, 95% CI [.55, 1.53], P < .001) and depression ( b = .24, 95% CI [.11, .37], P = .012), as were thermoregulatory symptoms (anxiety: b = 1.06, 95% CI [.46, 1.65], P = .004; depression: b = .25, 95% CI [.09, .42], P = .013), while cardiovascular ( b = .36, 95% CI [.10, .62], P = .012) and urinary symptoms ( b = .10, 95% CI [.01, .20], P = .037) were associated only with depression. Longitudinally, higher total autonomic load was associated with increases in both depression ( b = .01, 95% CI [.00, .02], P = .015) and anxiety ( b = .04, 95% CI [.01, .06], P < .001) over time, as well as occasion-to-occasion fluctuations (depression: b = .08, 95% CI [.05, .10], P < .001; anxiety: b = .24, 95% CI [.15, .32], P < .001)., Conclusion: Findings suggest autonomic dysfunction, particularly gastrointestinal and thermoregulatory symptoms, may be an indicator for elevated anxiety/depression and a potential treatment target early on in PD., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: The authors have read the journal’s policy and have the following competing interests: AdH has received consultant fees from Integra and Novo Nordisk outside of the submitted work. AdH has also received royalty fees from UpToDate outside of the submitted work. AdH also has equity in TitinKM and Certus outside of the submitted work. KS reports compensation from Sense and Zoll for data and safety monitoring services outside of the submitted work. KS also received consultant fees from Cerevasc, CSL Behring, Astrocyte Pharmaceuticals, Rhaeos, and Certus outside of the submitted work. KS also declares the following patent application associated with this research: Stroke wearables licensed to Alva Health. WTK reports sponsored research agreements from Hyperfine, Biogen, and NControl Therapeutics outside of the submitted work. WTK has also received consultant fees from Biogen, NControl Therapeutics, Acasti Pharma, and Astrocyte Pharmaceuticals outside of the submitted work. WTK also reports equity options from Acasti Pharma and equity from Woolsey Pharmaceuticals outside of the submitted work. SP reports funding from UpToDate as a contributor, and salary support from NIH and AHRQ as an investigator, outside of the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Havenon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Cerebral vasospasm in patients after aneurysmal subarachnoid hemorrhage (aSAH) continues to be a major source of morbidity despite significant clinical and basic science research. The removal of blood and its degradation products from the subarachnoid space through prophylactic lumbar drainage (LD) is a favorable option. However, several studies have delivered conflicting conclusions on its efficacy after aSAH., Methods: Systematic searches of Medline, Embase, and Cochrane Central Register of Controlled Trials were performed. The primary outcome was a good functional outcome (modified Rankin scale score, 0-2). Secondary outcomes included symptomatic vasospasm, secondary cerebral infarction, and mortality., Results: A total of 14 studies reporting on 2473 patients with aSAH were included in the meta-analysis. Compared with the non-LD group, no significant differences were found in the rates of good functional outcomes in the LD group at discharge to 1 month (risk ratio [RR], 1.28; 95% confidence interval [CI], 0.64-2.58) or at 6 months (RR, 1.12; 95% CI, 0.97-1.41). These findings were consistent in the subgroup analyses of only randomized controlled trials or observational studies. LD was associated with lower rates of symptomatic vasospasm (RR, 0.61; 95% CI, 0.48-0.77), secondary cerebral infarction (RR, 0.59; 95% CI, 0.45-0.79), and mortality at discharge to 1 month (RR, 0.58; 95% CI, 0.41-0.82). The effect on mortality diminished at 6 months (RR, 0.70; 95% CI, 0.34-1.45). However, when analyzing only randomized controlled trials, the benefit of LD on lower rates of mortality continued even at 6 months (RR, 0.75; 95% CI, 0.58-0.99)., Conclusions: For aSAH patients, the use of LD is associated with benefits in the rates of vasospasm, secondary cerebral infarctions, and mortality, without an increased risk of adverse events., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Cardiac autonomic neuropathy is a highly prevalent pathology in the diabetic population, and is the leading cause of death in this population. Orthostatic hypotension is the main clinical manifestation of the disease. In some patients, this orthostatic hypotension is associated with supine hypertension, posing a therapeutic challenge since treatment of one entity may aggravate the other. The challenge is to manage each of these two hemodynamic opposites without exposing the patient to a life-threatening risk of severe hypotension or hypertension., Case Presentation: We report a case of a 62-year-old ethnic Moroccan woman who has cardiovascular risk factors such as type 2 diabetes, arterial hypertension, and dyslipidemia. The patient's symptoms included dizziness, tremors, morning sickness, palpitations, and intolerance to exertion. Given her symptomatology, the patient benefited from an exploration of the autonomic nervous system through cardiovascular reactivity tests (Ewing tests), which confirmed the diagnosis of cardiac autonomic neuropathy. In addition to orthostatic hypotension, our patient had supine arterial hypertension, complicating management. To treat orthostatic hypotension, we advised the patient to avoid the supine position during the day, to raise the head of the bed during the night, and to have a sufficient fluid intake, with a gradual transition from decubitus to orthostatism and venous restraint of the lower limbs. Supine hypertension was treated with transdermal nitrates placed at bedtime and removed 1 hour before getting up. One week after the introduction of treatment, the patient reported a clear regression of functional symptoms, with an improvement in her quality of life. Improvement in symptomatology was maintained during quarterly follow-up consultations., Conclusions: Cardiac autonomic neuropathy is a very common pathology in diabetic patients. It is a serious condition with a life-threatening prognosis. Its management must be individualized according to the symptomatology and profile of each patient. The treatment of patients with orthostatic hypotension and supine hypertension requires special attention to ensure that each entity is treated without aggravating the other., (© 2024. The Author(s).)

Background: The purpose of this study was to determine the detailed characteristics of dizziness in patients with de novo Parkinson's disease (PD) and the clinical implications of dizziness., Methods: Ninety-three people with de novo PD were enrolled between July 2017 and August 2022 for this retrospective study. Using each representative scale, various motor and non-motor symptoms were assessed. In addition, clinical manifestations of dizziness in those patients, including its presence, type, frequency, and duration of occurrence, were investigated., Results: Thirty-nine patients with de novo PD reported dizziness, with presyncope being the most common (38%). The most common frequency was several times a week (51%). The most common duration was a few seconds (67%). Multivariable logistic regression analysis showed that dizziness was more common in women than in men {odds ratio (OR): 3.3601, 95% confidence interval (CI): 1.0820-10.4351, p = 0.0361}. Dizziness was significantly related to non-motor symptoms of low global cognition (OR: 0.8372, 95% CI: 0.7285-0.9622, p = 0.0123) and severe autonomic dysfunction (OR: 1.1112, 95% CI: 1.0297-1.1991, p = 0.0067). A post-hoc analysis revealed that dizziness was only associated with cardiovascular dysautonomia (adjusted OR: 10.2377, 95% CI: 3.3053-31.7098, p < 0.0001) among several domains of dysautonomia., Conclusions: About 42% of patients with de novo PD complained of dizziness. The occurrence of dizziness in those people was highly associated with female gender women, cognitive impairment, and cardiovascular dysautonomia. These results suggest that clinicians should pay close attention when patients with PD complain of dizziness., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Objective: This article discusses the effects of myelopathy on multiple organ systems and reviews the treatment and management of some of these effects., Latest Developments: Recent advances in functional electrical stimulation, epidural spinal cord stimulation, robotics, and surgical techniques such as nerve transfer show promise in improving function in patients with myelopathy. Ongoing research in stem cell therapy and neurotherapeutic drugs may provide further therapeutic avenues in the future., Essential Points: Treatment for symptoms of spinal cord injury should be targeted toward patient goals. If nerve transfer for upper extremity function is considered, the patient should be evaluated at around 6 months from injury to assess for lower motor neuron involvement and possible time limitations of surgery. A patient with injury at or above the T6 level is at risk for autonomic dysreflexia, a life-threatening condition that presents with elevated blood pressure and can lead to emergent hypertensive crisis. Baclofen withdrawal due to baclofen pump failure or programming errors may also be life-threatening. Proper management of symptoms may help avoid complications such as autonomic dysreflexia, renal failure, heterotopic ossification, and fractures., (Copyright © 2024 American Academy of Neurology.)

Cardiovascular autonomic neuropathy (CAN) is a frequent complication of diabetes mellitus and is associated with increased morbidity and mortality in patients with diabetes. Hence, early and correct diagnosis of CAN is crucial. Standard cardiovascular reflex rests (CARTs) have been the gold standard of CAN assessment. Originally, CARTs consisted of five reflex tests, but measuring diastolic blood pressure response to sustained handgrip exercise has no longer been suggested as an established clinical test. Increasing body of evidence suggests that isometric handgrip test should no longer be used for the evaluation of sympathetic dysfunction during cardiovascular autonomic neuropathy assessment in diabetic patients. The associations of isometric handgrip test results with parameters of hypertension and markers of hypertension-related target-organ damage in diabetic and non-diabetic individuals point toward its potential role as a screening tool to identify patients with high cardiovascular risk. The current review summarizes historical view of standard cardiovascular reflex tests and latest data on isometric handgrip test., Competing Interests: Declaration of competing interest The authors have no conflicting interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Autonomic Nervous System (ANS) dysfunction may be involved in the pathogenesis of Cerebral Small Vessel Disease (CSVD). The study aimed to explore the relationship between Recent Small Subcortical Infarct (RSSI) and Blood Pressure Variability (BPV), and Heart Rate Variability (HRV)., Methods: A total of 588 patients from the CSVD registration research database of Henan Province were included in this study, and were divided into two groups according to the presence of RSSI. Clinical data, including demographic characteristics, disease history, laboratory indexes, 24-hour ambulatory blood pressure and electrocardiogram indicators, and imaging markers of CSVD, were collected. Univariate and binary logistic regression analyses were used to study the relationship between RSSI and indicators of laboratory, HRV and BPV in the CSVD population., Results: Multivariate analysis showed that higher 24-hour mean Diastolic Blood Pressure (DBP)[Odds Ratios (OR)=1.083,95% Confidence Intervals (CI)=(1.038,1.129), p < 0.001], Standard Deviation (SD) of 24-hour DBP [OR=1.059,95%CI=(1.000,1.121), p = 0.049], nocturnal mean Systolic Blood Pressure (SBP) [OR=1.020,95%CI=(1.004,1.035), p = 0.012], nocturnal mean DBP [OR=1.025,95%CI=(1.009,1.040), p = 0.002] were independent risk factors for RSSI. In contrast, the decrease of the standard deviation of N-N intervals (SDNN) [OR=0.994,95%CI=(0.989,1.000), p = 0.035] was beneficial to the occurrence of RSSI. In addition, neutrophil counts [OR=1.138,95%CI=(1.030,1.258), p = 0.011], total cholesterol (TC) [OR=1.203,95%CI=(1.008,1.437), p = 0.041] and High-Density Lipoprotein (HDL) [OR=0.391, 95%CI=(0.195,0.786), p = 0.008] were also independently associated with the occurrence of RSSI. After adjusting for confounding factors, except for TC, the other factors remained associated with the occurrence of RSSI., Conclusion: Increased 24-hour mean DBP, nocturnal mean SBP and DBP, SD of 24-hour DBP and decreased SDNN were independently correlated with RSSI occurrence, suggesting that sympathetic overactivity plays a role in the pathogenesis of RSSI., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Postprandial hypotension is a type of autonomic dysfunction where there is a decrease in systolic blood pressure of >20 mm HG within 2 h after eating thought to be due to poor cardiovascular compensation for splanchnic blood pooling that occurs with meals. This form of autonomic dysfunction is underdiagnosed in patients with spinal cord injury, likely in part because it can be asymptomatic., Case Presentation: 26-year-old with complete cervical spinal cord injury (SCI) presented with neck pain described as severe 10/10 pain, which felt like "a rope around his neck." Pain came on during and after meals and was associated with a feeling of pressure behind his eyes, white spots in his vision along with feeling as if he was going to pass out. The caregiver noted a systolic blood pressure drop by about 30-40 points with meals and lost weight due to avoiding eating. A diagnosis of post-prandial hypotension (PPH) was made and Acarbose was started at a low dose 25 mg three times per day with meals. During follow up, the patient reported complete resolution of drops of blood pressure, neck pain, and all associated symptoms. The patient was able to eat comfortably and gained weight., Discussion: There are few case reports on PPH in SCI and none looking at acarbose on a young, nondiabetic person with SCI. Clinicians should be aware that PPH can occur in young otherwise healthy people with SCI. Further research is needed on PPH, including the use of acarbose, in the SCI population., (© 2023. The Author(s), under exclusive licence to International Spinal Cord Society.)

Competing Interests: Competing interests: None declared.

Traumatic and non traumatic spinal cord injury are rare and an orphan disease in comparison to common diseases. Those affected represent a very special patient population in the treatment even at the site of the accident and in emergency medicine and require a high level of professional expertise. The rehabilitation with the complexity of a spinal cord injury can only succeed with a multiprofessional team that is less focused on the often similar diagnoses according to the International Classification of Diseases (ICD) but on functional disorders and associated activity impairments. Only then the best possible integration and participation/inclusion in sociocultural and professional life can be achieved. In addition to the importance of classical physiotherapy and occupational therapy, this article highlights important but often missing team players, such as neurourology and electrical stimulation. In addition, the problems of frequent and some less recognized complications, such as autonomic dysfunction and the benefits of airway management are highlighted. For a comprehensive overview of rehabilitation in spinal cord injury, reference textbooks and guidelines are recommended that are cited in the text., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

The relationship between urinary endothelial growth factor (uEGF) and cardiovascular autonomic neuropathy (CAN) in adults with type 1 diabetes was evaluated. uEGF levels at baseline and standardized CAN measures were collected at baseline and annually for 3 years for type 1 diabetes adults. Linear regression analysis and linear mixed effects model were used for analysis. In this cohort (n = 44, 59% women, mean ± standard deviation age 34 ± 13 years and diabetes duration 14 ± 6 years), lower baseline uEGF levels correlated with lower baseline expiration : inspiration ratios (P = 0.03) and greater annual declines in Valsalva ratios (P = 0.02) in the unadjusted model, and correlated with lower low-frequency power : high-frequency power ratios (P = 0.01) and greater annual changes in low-frequency power : high-frequency power ratios (P = 0.01) after adjustment for age, sex, body mass index, and hemoglobin A1C. In conclusion, baseline uEGF levels correlate to baseline and longitudinal changes in CAN indices. A large-scale, long-term study is needed to validate uEGF as a reliable CAN biomarker., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Context: Hyperglycemia and autonomic dysfunction are bidirectionally related., Objective: We investigated the association of longitudinal evolution of heart rate variability (HRV) with incident type 2 diabetes (T2D) among the general population., Methods: We included 7630 participants (mean age 63.7 years, 58% women) from the population-based Rotterdam Study who had no history of T2D and atrial fibrillation at baseline and had repeated HRV assessments at baseline and during follow-up. We used joint models to assess the association between longitudinal evolution of heart rate and different HRV metrics (including the heart rate-corrected SD of the normal-to-normal RR intervals [SDNNc], and root mean square of successive RR-interval differences [RMSSDc]) with incident T2D. Models were adjusted for cardiovascular risk factors. Bidirectional Mendelian randomization (MR) using summary-level data was also performed., Results: During a median follow-up of 8.6 years, 871 individuals developed incident T2D. One SD increase in heart rate (hazard ratio [HR] 1.20; 95% CI, 1.09-1.33), and log(RMSSDc) (HR 1.16; 95% CI, 1.01-1.33) were independently associated with incident T2D. The HRs were 1.54 (95% CI, 1.08-2.06) for participants younger than 62 years and 1.15 (95% CI, 1.01-1.31) for those older than 62 years for heart rate (P for interaction <.001). Results from bidirectional MR analyses suggested that HRV and T2D were not significantly related to each other., Conclusion: Autonomic dysfunction precedes development of T2D, especially among younger individuals, while MR analysis suggests no causal relationship. More studies are needed to further validate our findings., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: To assess autonomic function and investigate factors related to its dysfunction in patients with temporomandibular disorders (TMD) from a biopsychosocial perspective., Methods: Seventy-six patients with TMD were investigated by clinical examination and questionnaires concerning biopsychosocial aspects (The Brief Pain Inventory, the Pain Catastrophizing Scale, and the Symptom Checklist-90-Revised) and autonomic dysfunction (The COMPASS 31)., Results: Seventy-one patients were included in the study. The result of multiple regression analysis showed that four variables (sex, depression, age, and pain interference) were significantly associated with autonomic dysfunction. Increased orthostatic intolerance and bladder dysfunction were observed in females and males, respectively. Younger age was associated with higher orthostatic intolerance, while higher pain interference was associated with higher secretomotor dysfunction and bladder dysfunction. Further, higher depression scores were linked to higher scores in the gastrointestinal subdomain., Conclusion: Autonomic dysfunction may affect TMD-related pain in the context of a biopsychosocial perspective.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor symptoms, including bradykinesia, resting tremor, and progressive rigidity. More recently, non-motor symptoms of PD, such as pain, depression and anxiety, and autonomic dysfunction, have attracted increasing attention from scientists and clinicians. As one of non-motor symptoms, pain has high prevalence and early onset feature. Because the mechanism of PD-related pathological pain is unclear, the clinical therapy for treating PD-related pathological pain is very limited, with a focus on relieving the symptoms. This paper reviewed the clinical features, pathogenesis, and therapeutic strategies of PD-related pathological pain and discussed the mechanism of the chronicity of PD-related pathological pain, hoping to provide useful data for the study of drugs and clinical intervention for PD-related pathological pain.

Various neurological disturbances in mental status, cognitive function, emotion, and motor function are observed owing to hypo- or hyperthyroidism. Although excretion of thyroid hormones is tightly regulated by the hypothalamus-pituitary gland-thyroid axis, it is partly influenced by blood flow regulated by the postsynaptic sympathetic fibers. In patients with Parkinson's disease in early stages, previous studies using cardiac MIBG scintigraphy or fluorodopa positron emission tomography showed mild-to-moderate denervation of the thyroid. However, whether the autonomic denervation of the thyroid may influence its excretion function, potentially leading to systemic metabolic changes originating from other organs, remains unclear. In this context, we examined the association of thyroid function with Parkinson's disease focusing on the autonomic nervous system referring to our latest achievement. Cardiac MIBG scintigraphy identified decreased uptake of the thyroid especially in early stages of Parkinson's disease with constipation, implying systemic autonomic denervation. Using multiomics analyses, we identified that the autonomic denervation-hypothyroidism-liver axis presented with insufficient fatty acid β-oxidation in patients with de novo Parkinson's disease.

A 56-year-old man presented to the clinic with episodic headaches for several years which had been worsening over a few months prior to the presentation. He described headache as sharp, stabbing pain around the left eye associated with nausea, vomiting, photophobia, and phonophobia lasting for hours associated with flushing on the left side of the face. The picture of his face during these episodes showed flushing of the left side of the face, ptosis of the right eyelid, and miosis (panel A). Flushing in his face would resolve with the abortion of the headache. At the time of presentation to the clinic, his neurological exam was only significant for mild left eye ptosis and miosis (panels B and C). Extensive workup including MRI brain, cervical spine, thoracic spine, lumbar spine, CTA head and neck, and CT maxillofacial was unremarkable. He had tried several medications in the past including valproic acid, nortriptyline, and verapamil without significant benefit. He was started on erenumab for migraine prophylaxis and was given sumatriptan for abortive therapy following which his headaches improved. The patient was diagnosed with idiopathic left Horner's syndrome and his migraines with autonomic dysfunction would present with unilateral flushing opposite to the site of Horner's presenting as Harlequin syndrome [1, 2]., (© 2023. Fondazione Società Italiana di Neurologia.)

Background: Resolution of sleep disordered breathing (SDB) in typically developing children normalises heart rate variability (HRV), a measure of autonomic control, to that of non-snoring controls. Children with Down Syndrome (DS) have dampened heart rate variability (HRV) but the effect of treatment is not known. To assess the effect of improvement of SDB on autonomic control we compared HRV in children with DS whose SDB improved over 2 y, to those whose SDB did not improve., Methods: 24 children (3-19 y) had a baseline and follow-up polysomnographic study 2 y later. Improved SDB was defined as a reduction in obstructive apnea hypopnea index (OAHI) to ≤ 50% of baseline. Children were grouped into Improved (n = 12) and Unimproved (n = 12). Power spectral analysis of the ECG determined low frequency (LF), high frequency (HF) power and the LF/HF ratio. Seven children in the Improved and 2 in the Unimproved group were treated following the baseline study., Results: In the Unimproved group at follow-up, LF power was lower compared to baseline during N3 and Total Sleep (p < 0.05 for both). HF power was lower during REM (p < 0.05). HRV remained unchanged between studies in the Improved group., Conclusion: Autonomic control worsened as indicated by lower LF and HF power in children whose SDB was not improved. In contrast, in those children with improved SDB, autonomic control remained the same, suggesting improvement in SDB severity prevents further worsening of autonomic control in children with DS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

High-level spinal cord injuries are often associated with autonomic impairment, which can result in orthostatic hypotension and syncope. Persistent autonomic dysfunction can manifest with disabling symptoms including recurrent syncopal events. We describe a case of autonomic failure resulting in recurrent syncopal events in a tetraplegic 66-year-old man., (© 2023. The Author(s), under exclusive licence to International Spinal Cord Society.)

Objective: To retrospectively describe ocular abnormalities reported in dogs with presumed dysautonomia., Animals: 79 dogs with dysautonomia., Methods: Medical records from the Kansas State University Veterinary Health Center from 2004 to 2021 were reviewed for dogs with a clinical or histopathologic diagnosis of canine dysautonomia (CD). Ophthalmic exam abnormalities, nonocular clinical signs, and outcomes were recorded., Results: Most dogs (73/79 [92.4%]) with CD exhibited at least 1 ocular abnormality. The most common ocular abnormalities were diminished pupillary light reflexes (PLRs) in 55 of 79 (69.6%) dogs and elevation of the third eyelids in 51 of 79 (64.6%) dogs. Schirmer tear test values were bilaterally decreased in 32 of 56 (57.1%) dogs. Other ocular abnormalities included resting mydriasis, ocular discharge, photophobia, blepharospasm, corneal ulceration, and conjunctival vessel pallor. The most common nonocular clinical signs were vomiting or regurgitation in 69 of 79 (87.3%) and diarrhea in 34 of 79 (43.0%) dogs. Pharmacologic testing with dilute 0.01%, 0.05%, or 0.1% pilocarpine yielded pupillary constriction in 42 of 51 (82.4%) dogs. Thirty-two of 79 (40.5%) dogs survived to discharge. Resolution of ocular abnormalities was variable., Clinical Relevance: Ophthalmic abnormalities such as diminished PLRs, elevation of the third eyelids, and decreased tear production are commonly associated with CD and provide support for its antemortem clinical diagnosis, though dogs with normal PLRs can be diagnosed with the disease. Pharmacologic testing with dilute topical pilocarpine in dogs with clinical signs suggestive of dysautonomia supports a diagnosis of CD. Ophthalmic abnormalities may improve or resolve over time.

Disorders of autonomic functions are typically characterized by disturbances in multiple organ systems. These disturbances are often comorbidities of common and rare diseases, such as epilepsy, sleep apnea, Rett syndrome, congenital heart disease or mitochondrial diseases. Characteristic of many autonomic disorders is the association with intermittent hypoxia and oxidative stress, which can cause or exaggerate a variety of other autonomic dysfunctions, making the treatment and management of these syndromes very complex. In this review we discuss the cellular mechanisms by which intermittent hypoxia can trigger a cascade of molecular, cellular and network events that result in the dysregulation of multiple organ systems. We also describe the importance of computational approaches, artificial intelligence and the analysis of big data to better characterize and recognize the interconnectedness of the various autonomic and non-autonomic symptoms. These techniques can lead to a better understanding of the progression of autonomic disorders, ultimately resulting in better care and management., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

The manifestations of diabetic autonomic neuropathy (DAN) are protean and clinically involve multiple systems, including the cardiovascular system, the gastrointestinal system, the genitourinary system as well as the sweat glands (sudomotor dysfunction) and the gallbladder. In addition, cardiac autonomic neuropathy (CAN) is associated with a correctible inability to appreciate and correct hypoglycaemia. While not a clinical problem, pupillary involvement should be the clue and the catalyst to investigate for other manifestations of DAN. This review outlines a practical approach to detecting and investigating the manifestations of DAN. Of particular importance is early detection of cardiovascular involvement where prompt therapy through glycaemic control can decrease the severity of CAN and decelerate the frequency and severity of retinopathy and nephropathy in addition to decreasing cardiovascular events and mortality. CAN also plays a role in accelerating other diabetic complications such as acute ischaemic stroke, heart failure, medial artery calcinosis, foot ulcers, peripheral artery disease and Charcot joints. Many therapies of DAN are available, which should not only decrease morbidity and mortality from DAN, but also improve the patient's quality of life. However, the therapies available are largely symptomatic., (© 2023 John Wiley & Sons Ltd.)

We describe a man in his 40s with a history of chronic intranasal cocaine use and C5-C7 incomplete quadriplegia complicated by neurogenic orthostatic hypotension, admitted to the intensive care unit for worsening bradycardia and hypotension requiring initiation of dopamine and an increase of his home midodrine dose. The patient experienced refractory bradycardia and hypotension with weaning of dopamine, and therefore a recommendation was made to add pseudoephedrine to his current regimen. This case describes the addition of pseudoephedrine to facilitate weaning off intravenous vasopressors within 24 hours in a patient with refractory bradycardia and hypotension secondary to autonomic dysfunction., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective : This work aimed to determine the relationship between the autonomic nervous system and reactive hyperemia (RH) in type 2 diabetes patients with and without cardiovascular autonomic neuropathy (CAN). Methodology : A systematic review of randomized and nonrandomized clinical studies characterizing reactive hyperemia and autonomic activity in type 2 diabetes patients with and without CAN was performed. Results : Five articles showed differences in RH between healthy subjects and diabetic patients with and/or without neuropathy, while one study did not show such differences between healthy subjects and diabetic patients, but patients with diabetic ulcers had lower RH index values compared to healthy controls. Another study found no significant difference in blood flow after a muscle strain that induced reactive hyperemia between normal subjects and non-smoking diabetic patients. Four studies measured reactive hyperemia using peripheral arterial tonometry (PAT); only two found a significantly lower endothelial-function-derived measure of PAT in diabetic patients than in those without CAN. Four studies measured reactive hyperemia using flow-mediated dilation (FMD), but no significant differences were reported between diabetic patients with and without CAN. Two studies measured RH using laser Doppler techniques; one of them found significant differences in the blood flow of calf skin after stretching between diabetic non-smokers and smokers. The diabetic smokers had neurogenic activity at baseline that was significantly lower than that of the normal subjects. The greatest evidence revealed that the differences in RH between diabetic patients with and without CAN may depend on both the method used to measure hyperemia and that applied for the ANS examination as well as the type of autonomic deficit present in the patients. Conclusions : In diabetic patients, there is a deterioration in the vasodilator response to the reactive hyperemia maneuver compared to healthy subjects, which depends in part on endothelial and autonomic dysfunction. Blood flow alterations in diabetic patients during RH are mainly mediated by sympathetic dysfunction. The greatest evidence suggests a relationship between ANS and RH; however, there are no significant differences in RH between diabetic patients with and without CAN, as measured using FMD. When the flow of the microvascular territory is measured, the differences between diabetics with and without CAN become evident. Therefore, RH measured using PAT may reflect diabetic neuropathic changes with greater sensitivity compared to FMD.

The Autonomic Nervous System (ANS) regulates many critical physiological functions. Its control relies on cortical input, especially limbic areas, which are often involved in epilepsy. Peri-ictal autonomic dysfunction is now well documented, but inter-ictal dysregulation is less studied. In this review, we discuss the available data on epilepsy-related autonomic dysfunction and the objective tests available. Epilepsy is associated with sympathetic-parasympathetic imbalance and a shift towards sympathetic dominance. Objective tests report alterations in heart rate, baroreflex function, cerebral autoregulation, sweat glands activity, thermoregulation, gastrointestinal and urinary function. However, some tests have found contradictory results and many tests suffer from a lack of sensitivity and reproducibility. Further study on interictal ANS function is required to further understand autonomic dysregulation and the potential association with clinically-relevant complications, including risk of Sudden Unexpected Death In Epilepsy (SUDEP)., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objective: Autonomic disorders are common in chronic illness, and their symptoms may restrict the daily functioning of patients. However, in chronic heart failure, extensive knowledge about autonomic symptoms is still lacking. This study aims to explore self-perceived autonomic symptoms, associated factors, and their relationship with health-related quality of life in chronic heart failure., Methods: One hundred and twenty-four patients with documented chronic heart failure (men and women; 50-86 years) and 124 sex and age-matched controls participated in this study. The participants filled validated questionnaires about autonomic symptom profile (COMPASS 31), fatigue (CIS, Checklist for individual strength), anxiety and depression (HADS, Hospital Anxiety and Depression), and health-related quality of life (SF36). Non-parametric statistics were performed to analyse the data., Results: Total score for autonomic symptoms was higher in chronic heart failure compared to controls [Median: 14.9; IQR: 6.2-25.1 vs. 7.3; 0-18; p  < 0.001], especially for orthostatic hypotension [Median: 8; IQR: 0-16 vs. 0; 0-12; p  < 0.001], vasomotor [Median: 0; IQR: 0-0 vs. 0; 0-0; p  < 0.001] and secretomotor function [Median: 0; IQR: 0-4.2 vs. 0; 0-2.1; p  = 0.013]. High scores for autonomic symptoms were moderate correlated with higher scores of fatigue, anxiety and depression (0.343 ≤  r s ≥ 0.420; p  < 0.001) and with decreased health-related quality of life (-0.454; p  < 0.01)., Conclusion: Autonomic symptoms, especially for orthostatic intolerance, vasomotor and secretomotor subdomains, are prevalent and are associated with fatigue complaints and poor health-related quality of life in CHF.

We herein report a 45-year-old man with dentatorubropallidoluysian atrophy (DRPLA) who presented with mild dementia, ataxia, and involuntary movement and developed constipation, dysuria, and orthostatic hypotension. Thermography revealed an abnormal thermal response of the skin to cold stimulation. Skin temperature reflects the skin blood flow and is regulated by the sympathetic nervous system. Thermography is currently used to study diseases associated with vasomotor dysfunction of the skin. The thermography results suggested the possibility of autonomic dysfunction. Although little is known regarding autonomic dysfunction in DRPLA, this report demonstrates the importance of autonomic dysfunction in DRPLA.

Objective: The role of hemorrhage volume in risk of vasospasm, delayed cerebral ischemia (DCI), and poor outcomes after aneurysmal subarachnoid hemorrhage (SAH) is well established. However, the relative contribution of blood within individual compartments is unclear. We present an automated technique for measuring not only total but also volumes of blood in each major compartment after SAH., Methods: We trained convolutional neural networks to identify compartmental blood (cisterns, sulci, and ventricles) from baseline computed tomography scans of patients with SAH. We compared automated blood volumes against traditional markers of bleeding (modified Fisher score [mFS], Hijdra sum score [HSS]) in 190 SAH patients for prediction of vasospasm, DCI, and functional status (modified Rankin Scale) at hospital discharge., Results: Combined cisternal and sulcal volume was better correlated with mFS and HSS than cisternal volume alone (ρ = 0.63 vs. 0.58 and 0.75 vs. 0.70, P < 0.001). Only blood volume in combined cisternal plus sulcal compartments was independently associated with DCI (OR 1.023 per mL, 95% CI 1.002-1.048), after adjusting for clinical factors while ventricular blood volume was not. Total and specifically sulcal blood volume was strongly associated with poor outcome (OR 1.03 per mL, 1.01-1.06, P = 0.006 and OR 1.04, 1.00-1.08 for sulcal) as was HSS (OR 1.06 per point, 1.00-1.12, P = 0.04), while mFS was not (P = 0.24)., Conclusions: An automated imaging algorithm can measure the volume of bleeding after SAH within individual compartments, demonstrating cisternal plus sulcal (and not ventricular) blood contributes to risk of DCI/vasospasm. Automated blood volume was independently associated with outcome, while qualitative grading was not., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Xerosis is an extremely common condition, especially in the elderly population. It is the most common cause of pruritus in the older adult. Since xerosis is generally caused by a lack of epidermal lipids, the use of leave-on skin care products is the mainstay treatment. The aim of this open prospective analytical observational study was to investigate the clinical and self-reported hydrating efficacy of a moisturizer formulation containing a synergy between amino-inositol and urea (INOSIT-U 20) in patients with psoriasis and xerosis., Methods: Twenty-two patients with psoriasis successfully treated with biologic therapy, and who presented xerosis, were recruited. Each patient was instructed to apply the topical with a frequency of two applications per die on the identified skin area. Corneometry values and a VAS itch questionnaire were measured at baseline (T0) and after 28 days (T4). To evaluate the cosmetic efficacy, the volunteers also completed a self-assessment questionnaire., Results: Comparing Corneometry values at T0 and T4, a statistically significant increase value was observed in the area subjected to topical treatment (P<0.0001). A significant decrease in itch (P=0.001) was also observed. Moreover, the patients' ratings of the cosmetic properties of the moisturizer showed significant confirmation rates., Conclusions: This study provides preliminary evidence that INOSIT-U20 provides a good hydrating effect on xerosis, further reducing self-reported itch.

This case demonstrates how orthostatic hypotension in the absence of typical symptoms of light-headedness/dizziness when changing posture, can contribute to the burden of falls in Parkinson's disease. At least one-third of people with severe orthostatic hypotension do not report typical symptoms, and this figure appears to be higher in patients with Parkinson's disease. This is important clinically as it can increase the difficulty in ascribing falls to orthostatic hypotension, especially given the other competing reasons in Parkinson's disease and orthostatic hypotension symptoms can act as a prompt for the patient to act to prevent falls-related injuries. There is a clinical requirement, therefore, to screen for and manage orthostatic hypotension in patients with Parkinson's disease to prevent falls, even in those who do not report typical symptoms., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Identification of metabolomics profile in subjects with different blood pressure, including normal blood pressure, elevated blood pressure, stage 1 hypertension, and stage 2 hypertension, would be a promising strategy to understand the pathogenesis of hypertension. Thus, we conducted this study to investigate the association of plasma acylcarnitines and amino acids with hypertension in a large Iranian population., Methods: 1200 randomly selected subjects from the national survey on the Surveillance of Risk Factors of Non-Communicable Diseases in Iran (STEPs 2016) were divided into four groups based on the ACC/AHA hypertension criteria: normal blood pressure (n = 293), elevated blood pressure (n = 135), stage 1 hypertension (n = 325), and stage 2 hypertension (n = 447). Plasma concentrations of 30 acylcarnitines and 20 amino acids were measured using a targeted approach with flow-injection tandem mass spectrometry. Univariate and multivariate logistic regression analysis was applied to estimate the association between metabolites level and the risk of hypertension. Age, sex, BMI, total cholesterol, triglyceride, HDL cholesterol, fasting plasma glucose, use of oral glucose-lowering drugs, statins, and antihypertensive drugs were adjusted in regression analysis., Results: Of 50 metabolites, 34 were associated with an increased likelihood of stage 2 hypertension and 5 with a decreased likelihood of stage 2 hypertension. After full adjustment for potential confounders, 5 metabolites were still significant risk markers for stage 2 hypertension including C0 (OR = 0.75; 95%CI: 0.63, 0.90), C12 (OR = 1.18; 95%CI: 1.00, 1.40), C14:1 (OR = 1.20; 95%CI: 1.01, 1.42), C14:2 (OR = 1.19; 95%CI: 1.01, 1.41), and glycine (OR = 0.81; 95%CI: 0.68, 0.96). An index that included glycine and serine also showed significant predictive value for stage 2 hypertension after full adjustment (OR = 0.86; 95%CI: 0.75, 0.98)., Conclusions: Five metabolites were identified as potentially valuable predictors of stage 2 hypertension., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Arjmand et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To evaluate the influence of motor and autonomic disorders on the pain of patients with PD of the I-III H&Y stages and possibility of correcting the pain with dopamine receptor agonists (ADR)., Material and Methods: 252 patients (128 women and 124 men, 42-80 years old) with PD of I-III Hoehn and Yahr stages (H&Y) were examined using the following scales: UPDRS, daily activity Sch&En, quality of life PDQ-39, MMSE, BDI, PFS-16, NMSQuest, GSRS, AUA; 53 patients were piribedil treated during 6 months., Results: Our results indicated a wide prevalence of pain syndrome in PD patients (58.6%), starting from the early stages (50% for the Ist stage). The most stable pain associations were found with the PD stage, levodopa doses, severity of motor symptoms (postural disorders and hypokinesia manifestations) and motor complications («off-periods» and dyskinesias), as well as non-motor PD manifestations depression and autonomic dysfunctions (constipation, swallowing disorders, and frequent urination). The regression analysis showed, that the severity of motor complications and depression were the predictors of pain occurrence. The pain syndrome in patients with PD of I-III stages underwent significant regression (by 51% and 62%, after 1.5 and 6 months of therapy, respectively) after ADR (piribedil) addition to their therapy; it's probably due to improving the motor component and decreasing depressive disorders., Conclusions: The piribedil inclusion contributes to the reduction of pain syndrome, regardless is it used in monotherapy or in conjunction with levodopa preparations.

Objective: Cardiovascular autonomic neuropathy is a known complication in type 2 diabetes (T2D). However, the extent of sympathetic dysfunction and its relation to blood pressure (BP) dysregulation is insufficiently studied. We therefore assessed the cardiovascular sympathetic function using a standardized autonomic test-battery., Research Design and Methods: Forty T2D patients (mean age and duration of diabetes ±SD, 65.5 ± 7.3 and 9.5 ± 4.2 years) and 40 age- and gender-matched controls were examined through autonomic testing, assessing cardiovascular responses to deep breathing, Valsalva maneuver and tilt-table testing. Additionally, 24-hour oscillometric BP and self-reported autonomic symptoms on COMPASS-31 questionnaire was recorded., Results: Patients with T2D had reduced parasympathetic activity with reduced deep breathing inspiratory:expiratory-ratio (median [IQR] T2D 1.11 [1.08-1.18] vs. controls 1.18 [1.11-1.25] (p = 0.01)), and reduced heart rate variability (p < 0.05). We found no differences in cardiovascular sympathetic function measured through BP responses during the Valsalva maneuver (p > 0.05). 24-hour-BP detected reduced night-time systolic BP drop in T2D (9.8 % ± 8.8 vs. controls 15.8 % ± 7.7 (p < 0.01)) with more patients having reverse dipping. Patients with T2D reported more symptoms of orthostatic intolerance on the COMPASS-31 (p = 0.04)., Conclusions: Patients with T2D showed reduced parasympathetic activity but preserved short-term cardiovascular sympathetic function, compared to controls, indicating autonomic dysfunction with predominantly parasympathetic impairment. Despite this, T2D patients reported more symptoms of orthostatic intolerance in COMPASS-31 and had reduced nocturnal BP dipping, indicating that these are not a consequence of cardiovascular sympathetic dysfunction., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose of Review: This article reviews the pathophysiology, epidemiology, clinical features, diagnosis, and treatment of Lambert-Eaton myasthenic syndrome (LEMS) and botulism, presynaptic disorders of neuromuscular transmission in which rapid diagnosis improves long-term outcomes., Recent Findings: Therapy for LEMS has seen significant advances in recent years due to the approval of amifampridine-based compounds. LEMS is likely still underdiagnosed, particularly when no underlying malignancy is identified. Clinicians must have a strong suspicion for LEMS in any patient presenting with proximal weakness and autonomic dysfunction. Botulism is another rare disorder of presynaptic neuromuscular transmission that is most commonly associated with improper storage or preservation of food products. Over the past 2 decades, wound botulism has been increasingly reported among users of black tar heroin. A high degree of clinical suspicion and electrodiagnostic studies can be beneficial in distinguishing botulism from other acute neurologic disorders, and early involvement of state and federal health authorities may assist in confirming the diagnosis and obtaining treatment. When botulism is suspected, electrodiagnostic studies can provide clinical evidence of disordered neuromuscular transmission in advance of serologic confirmation, and providers should not wait for confirmation of the diagnosis to initiate treatment., Summary: A targeted clinical history and a thorough neurologic examination with support from serologic and electrodiagnostic studies are key to early diagnosis of LEMS and botulism. Early diagnosis of both conditions creates opportunities for therapy and improves outcomes., (Copyright © 2022 American Academy of Neurology.)

The presence of autonomic symptoms are a common part of the symptomatology of Parkinsońs disease (PD), with the potential to impact the quality of life of patients. The aim of this study was to assess the frequency of autonomic symptoms among Faroese PD patients compared to a control group, using the Scales for Outcome in Parkinson's Disease - Autonomic (SCOPA-AUT), and to determine the relationship between autonomic and motor symptoms in PD patients using the Unified Parkinsońs Disease Rating Scale - Part III (UPDRS) and Hoehn and Yahr Scale (H&Y). The study included 54 PD patients and 190 control individuals which were unaffected relatives. The mean SCOPA-AUT scores were significantly higher for PD patients in gastrointestinal (OR = 1.62), urinary (OR = 1.38), cardiovascular (OR = 1.65), thermoregulatory (OR = 1.54) and sexual dysfunction (OR = 1.71) scores, as well as the total score (OR = 1.26). UPDRS scores were significant correlated with SCOPA-AUT scores (p = 0.015), while H&Y scores were not (p = 0.103). In conclusion, PD patients experience an increased frequency of autonomic symptoms compared with controls and the frequency is associated with the motor symptoms assessed with UPDRS. Our findings are consistent with similar studies and our current understanding of PD pathology., (Copyright © 2022. Published by Elsevier B.V.)

Purpose: The superior and inferior tarsal muscles are sympathetically innervated smooth muscles. Long-term diabetes often leads to microvascular complications, such as, retinopathy and autonomic neuropathy. We hypothesized that diabetes induces (1) sympathetic paresis in the superior and inferior tarsal muscles and that this measure is associated with (2) the severity of diabetic retinopathy, (3) the duration of diabetes, and (4) autonomic function. In addition, association between the severity of retinopathy and autonomic function was investigated., Methods: Forty-eight participants with long-term type 1 diabetes and confirmed distal symmetrical polyneuropathy were included. Palpebral fissure heights were measured bilaterally in response to topically applied 10% phenylephrine to the right eye. The presence of proliferative diabetic retinopathy (PDR) or nonproliferative diabetic retinopathy and disease duration were denoted. Time and frequency derived heart rate variability parameters obtained from 24-hour continuous electrocardiography were recorded., Results: The difference in palpebral fissure heights between phenylephrine treated and untreated eyes (∆PFH) was 1.02 mm ± 0.29 (P = 0.001). The ∆PFH was significantly lower in the PDR group (0.41 mm ± 0.43 vs. 1.27 mm ± 1.0), F(1,35) = 5.26, P = 0.011. The ∆PFH was lower with increasing diabetes duration, r(37) = -0.612, P = 0.000. Further, the ∆PFH was lower with diminished autonomic function assessed as total frequency power in electrocardiogram (r = 0.417, P = 0.014), and sympathetic measures of very low (r = 0.437, P = 0.010) and low frequency power (r = 0.384, P = 0.025)., Conclusions: The ∆PFH is a simple ambulatory sympathetic measure, which was associated with the presence of PDR, disease duration, and autonomic function. Consequently, ∆PFH could potentially be an inexpensive and sensitive clinical indicator of autonomic dysfunction.

Background: Autoimmune autonomic ganglionopathy is a rare, immune-mediated disorder associated with anti-ganglionic α3-subunit nicotinic acetylcholine receptor (anti-α3gAChR) antibodies, which bind to acetylcholine receptor in autonomic ganglia (parasympathetic and sympathetic) leading to autonomic failure. This disorder is mostly associated with viral infections, but it can also be associated with systemic malignancies. Here, we report the case of a paraneoplastic autonomic ganglionopathy as the first symptom of bladder cancer., Method: Case report., Results: A 47-year-old man, without medical history of interest, stated to the emergency department for progressive blurry vision with eye and mouth dryness, constipation, and dizziness upon standing for the last 2 weeks. Orthostatic hypotension was demonstrated by a drop in 13.3 mmHg mean blood pressure (BP) from supine (100/60 mmHg) to 45° reclining sitting position (80/50 mmHg). Blood tests, chest X-ray, brain MRI, and electroneuronography were unremarkable. Electrochemical skin conductance was reduced. Serological examination was positive for anti-α3gAChR antibodies. A full-body CT scan revealed a bladder tumor, which was treated by transurethral bladder resection. The pathologic study demonstrated a low-grade non-muscle-invasive bladder urothelial carcinoma. After tumor resection, and treatment with intravenous immunoglobulins and corticoids, a gradually improvement was observed. Today, the patient remains asymptomatic., Conclusion: Subacute panautonomic failure can be the first symptom for systemic malignancies. This case reports a paraneoplastic autonomic ganglionopathy as the first symptom of bladder cancer. This case highlights the importance of a systemic study to rule out the presence of cancer when autoimmune autonomic ganglionopathy is present., (© 2022. Fondazione Società Italiana di Neurologia.)

Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is a rare complex disorder associated with alterations in the endocrine system, autonomic nervous system, and respiratory system. Previously published case reports and studies have noted sleep-disordered breathing in patients with ROHHAD syndrome. Nocturnal respiratory manifestations, which if untreated early by respiratory support, may cause cardiorespiratory arrest and a life-threatening condition. More recently, it has been recognized that children with ROHHAD syndrome have central pauses during wakefulness associated with intermittent oxygen desaturations. We report novel findings of a child with ROHHAD syndrome displaying an irregular breathing pattern and significant central pauses associated with oxygen desaturations during wakefulness, whose respiratory status improved while chewing gum. This was used as an alternative to supplemental oxygen therapy., Citation: Sunkonkit K, Selvadurai S, Yeh EA, Hamilton J, Narang I. Chewing gum: alternative therapy to oxygen intolerance. J Clin Sleep Med . 2022;18(6):1723-1726., (© 2022 American Academy of Sleep Medicine.)

To provide more insight in the delay in diagnosis and expectation of treatment adapted for the paediatrician, the data were collected from patients described with dopamine beta-hydroxylase deficiency are evaluated. More insight in clinical features of dopamine beta-hydroxylase deficiency consisting mainly of eyelid ptosis, orthostatic hypotension, hypoglycaemia and exercise intolerance, explains the delay in diagnosis of this congenital disorder, although all symptoms some more concealed are present. An increasing experience by L-DOPS, a resurrection for the patient, allows recommendations for early treatment. An explanation for the delay in diagnosis is provided together with the advice for treatment., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aims: We aimed to evaluate the contemporary prevalence of and risk factors for symptomatic diabetic autonomic neuropathy (DAN) in participants with type 1 diabetes (T1D) enrolled in the T1D Exchange Clinic Registry., Methods: DAN symptoms and severity were assessed with the Survey of Autonomic Symptoms (SAS) in adults with ≥5 years of T1D participating in the T1D Exchange from years 2010-2017. Associations of demographic, clinical, and laboratory factors with symptomatic DAN were assessed., Results: Of the 4919 eligible T1D participants, 965 (20%) individuals completed the SAS questionnaire [mean age 40 ± 17 years, median diabetes duration 20 years (IQR: 13,34), 64% female, 90% non-Hispanic White, and 82% with private insurance]. DAN symptoms were present in 166 (17%) of responders with 72% experiencing moderate severity symptoms or worse. Symptomatic DAN participants had higher hemoglobin A1c (p = 0.03), longer duration (p = 0.004), were more likely to be female (p = 0.03), and more likely to have lower income (p = 0.03) versus no DAN symptoms. Symptomatic DAN was associated with diabetic peripheral neuropathy (p < 0.0001), smoking (p = 0.002), cardiovascular disease (p = 0.02), depression (p < 0.001), and opioid use (p = 0.004)., Conclusions: DAN symptoms are common in T1D. Socioeconomic factors and psychological comorbidities may contribute to DAN symptoms and should be explored further., (Published by Elsevier Inc.)

Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus that can predispose patients to higher risk for cardiovascular death. The aim of the present study was to evaluate the presence of cardiac autonomic neuropathy and sudomotor dysfunction in patients with newly diagnosed carbohydrate disturbances (prediabetes or diabetes) and to assess their relationship to metabolic disturbances and cardiovascular risk. In the present study, we included 160 patients -78 with obesity without carbohydrate disturbances, 52 with prediabetes, and 30 with newly diagnosed diabetes. CAN was diagnosed using cardiovascular reflex tests and sudomotor function was evaluated by SUDOSCAN. Cardiovascular risk was calculated using SCORE and FRMINGHAM risk scores. The prevalence of cardiac autonomic neuropathy was significantly higher in patients with newly diagnosed diabetes. Independently of their glycemic status, the patients who had blood glucose on the 60th-minute of OGTT>8.5 mmol/l had significantly higher prevalence of cardiac autonomic neuropathy (30.2% vs 15.6%, р=0.044). Patients with high cardiovascular risk according to FRAMINGHAM and SCORE had worse heart rate variability scores. Autonomic neuropathy risk assessed by SUDOSCAN was a good predictor for the presence of CAN. In conclusion, CAN has a higher prevalence on patients with newly diagnosed diabetes compared to prediabetic and normoglycemic subjects, while the patients with blood glucose>8.5 mmol/l on the 60th-minute of OGTT have higher prevalence of CAN independently of their glycemic status. SUDOSCAN testing can be used to assess the risk of CAN and to select patients that should undergo further testing., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)