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.

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.

Gastrointestinal symptom burden in diabetic autonomic and peripheral neuropathy - A Danes cohort study.

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, HbA1C 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.

A therapeutic challenge relating to the association of orthostatic hypotension and supine hypertension in a patient with cardiac autonomic neuropathy: a case report.

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.

Clinical Characteristics and Relevance of Dizziness in Patients with de novo Parkinson's Disease.

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.

Symptomatic Treatment of Myelopathy.

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.

Effectiveness of Cerebrospinal Fluid Lumbar Drainage Among Patients with Aneurysmal Subarachnoid Hemorrhage: An Updated Systematic Review and Meta-Analysis.

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.

The handgrip test - A historical test for diabetic autonomic neuropathy or a marker of something else?

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.

The Relationship Between Autonomic Dysfunction and Mood Symptoms in De Novo Parkinson's Disease Patients Over Time.

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.

Management of Cholinergic Rebound After Abrupt Withdrawal of Clozapine: A Case Report and Systematic Literature Review.

BACKGROUND: Cholinergic discontinuation symptoms, also known as "cholinergic rebound," from abrupt clozapine discontinuation are characterized by a range of somatic and psychiatric symptoms. OBJECTIVE: The objective of this study was to describe the clinical features and management options for clozapine withdrawal-associated cholinergic rebound syndrome (henceforth referred to as CWCRS) and present an illustrative case report. METHODS: Based on a literature search of the databases PubMed, OVID Medline, and Embase as well as reviewing reference lists of relevant past reviews, we carried out a systematic review of case reports on the management of CWCRS from 1946 to 2023. RESULTS: We identified 10 previously published articles on the clinical management of CWCRS, with a total of 18 patients (6 female, 12 male) with an average age of 43 years (standard deviation 14). Half of the patients had a history of tardive dyskinesia. The mean dose of clozapine before discontinuation was 351 mg/day, with duration of clozapine treatment ranging from 3 weeks to 9 years. Clozapine was the most effective treatment, followed by benztropine. CONCLUSIONS: Given the small number of cases and the nonexperimental nature of the available studies, this review could not provide reliable data to guide management of CWCRS. The findings, however, suggest that clozapine may be more effective than other commonly used treatment options. With the high rates of discontinuation among patients on clozapine, there is a pressing need for further research into the epidemiology, natural history, and management of clozapine withdrawal syndromes.

Treatment of postprandial hypotension with acarbose in an adult with cervical spinal cord injury: a case report.

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.

[Rehabilitation after Spinal Cord Injury : Current trends and principles]. / Rehabilitation nach einer Querschnittlähmung : Aktuelle Trends und Grundlagen.

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.

[Association of Pathological Progression of Parkinson's Disease and the Thyroid Gland].

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 ß-oxidation in patients with de novo Parkinson's disease.

[Progress on the mechanism and treatment of Parkinson's disease-related pathological pain].

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.

Urinary epidermal growth factor levels correlate with cardiovascular autonomic neuropathy indices in adults with type 1 diabetes.

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.

Diminished pupillary light reflexes, elevated third eyelids, and decreased tear production are commonly associated with canine dysautonomia.

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.

Recurrent syncope secondary to autonomic dysfunction in spinal cord injury: a case report.

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.

A narrative review of the mechanisms and consequences of intermittent hypoxia and the role of advanced analytic techniques in pediatric autonomic disorders.

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.