Clinical and endocrine features of orthostatic intolerance detected in patients with long COVID.

Orthostatic intolerance (OI) is a key symptom of long COVID; however, the pathophysiology remains unknown. Among 688 long COVID patients who visited our clinic during the period from February 2021 to April 2023, 86 patients who were suspected of having OI and who underwent an active standing test (ST) were investigated to elucidate the clinical characteristics of OI in patients with long COVID. Of the 86 patients, 33 patients (38%) were ST-positive. Nausea and tachycardia in daily life were frequent complaints in the ST-positive group. The increase in heart rate (HR) during the ST was significantly greater during a 10-min period after standing in the ST-positive group (+ 30 bpm) than in the ST-negative group (+ 16 bpm). The initial increase in diastolic blood pressure (DBP) just after standing was significantly greater in the ST-positive group (+ 14 mmHg) than in the ST-negative group (+ 9 mmHg). Serum cortisol levels in the ST-positive patients aged over 20 years were higher and growth hormone levels in the patients under 20 years of age were lower than those in the ST-negative group. Autonomous nervous symptoms, transient DBP rise with increasing HR after standing, and endocrine dysfunctions are helpful for detecting OI related to long COVID.

Study on the similarities and differences of orthostatic hypotension in patients with Parkinson′s disease and multiple system atrophy / 中华神经科杂志

Objective:To summarize and compare the characteristics of orthostatic hypotension (OH)　in　patients　with　Parkinson′s disease and multiple system atrophy (MSA).Methods:The active standing test data of 210 Parkinson′s disease patients (Parkinson′s disease group) and 85 MSA patients (MSA group) admitted to the Department of Neurology, Xuanwu Hospital, Capital Medical University from January 2021 to March 2022 were retrospectively analyzed. Demographic information, clinical data, Hoehn-Yahr staging, and Unified Parkinson′s Disease Rating Scale (UPDRS), Non-Motor Symptoms Questionnaire (NMSQ), Montreal Cognitive Assessment Scale and Mini-Mental State Examination scores were collected. The comparative analysis of OH was conducted according to the changes of heart rate and blood pressure during the active standing test.Results:Among the 85 patients with MSA, 52 were found with MSA parkinsonism variant (MSA-P) and 33 with MSA cerebellar variant (MSA-C). The 210 Parkinson′s disease patients were aged (61.5±11.0) years, with 116 males (55.2%). The 85　MSA　patients　were aged (60.1±6.8) years, with 44 males (51.8%). Compared with the Parkinson′s disease group, the Hoehn-Yahr staging [2.0(2.0, 3.0) vs 3.0(2.0, 3.0), Z=-5.278, P<0.001], NMSQ[ 25.0(11.0,46.5) vs 45.0(24.0,70.0), Z=-3.632, P<0.001] and UPDRS scores [50.0(32.0,68.0) vs 65.5(44.5,78.5), Z=-3.073, P=0.003] in the MSA group were higher. The incidence of OH in the MSA group was higher than that in the Parkinson′s disease group [63.5% (54/85) vs 25.7%(54/210), χ 2= 37.284, P<0.001], but there was no statistically significant difference between the MSA-P and MSA-C groups . Compared with the Parkinson′s disease group, the MSA group had a higher incidence of classical OH [54.1%(46/85) vs 12.9%(27/210), χ 2=55.316, P<0.001] and neurogenic OH [36.5%(31/85) vs 9.0%(19/210), χ 2=32.326, P<0.001],but there was no statistically significant difference in the incidence of initial OH and delayed OH between the two groups. The incidence of severe OH in the MSA group was also higher than that in the Parkinson′s disease group [57.6%(49/85) vs 16.7%(35/210), χ 2=49.894, P<0.001], but there was no statistically significant difference in the incidence of pre-clinical OH and mild OH between the two groups. Conclusions:The incidence, time change, severity and pathophysiological basis of OH in Parkinson′s disease and MSA patients are different. Different types of OH may help to distinguish MSA from Parkinson′s disease.

The Effect of Epipharyngeal Abrasive Therapy (EAT) on the Baroreceptor Reflex (BR).

Introduction Epipharyngeal Abrasive Therapy (EAT) has been used as a treatment for chronic epipharyngitis, and although autonomic nerve stimulation has been pointed out as one of the mechanisms by which EAT produces therapeutic effects, there have been few reports examining this mechanism of action. This study investigated the effects of repeated EAT on autonomic nervous system activity in chronic epipharyngitis patients over time, using heart rate variability analysis. In addition, we conducted a loading test using the active standing test (AS test) to examine the effects of EAT on the baroreceptor reflex (BR). Subjects and methods A retrospective study was conducted on 39 patients who visited our clinic between July 2017 and November 2019 and underwent autonomic function tests with a diagnosis of chronic nasopharyngeal inflammation. The subjects were divided into two groups: the improvement group and the invariant group for comparison. Electrocardiographic recordings and blood pressure measurements were made under the stress of the AS test. Heart rate, high-frequency (HF) component, low-frequency (LF) component, and Coefficient of Variation on R-R interval were evaluated as indices of autonomic function. Component coefficient of variance high frequency was used as an index of parasympathetic function. ccvLF/ccvHF ratio was calculated by dividing the component coefficient of variance low frequency by ccvHF. The AS test was conducted in phase 1 in the initial resting sitting position, in phase 2 in the standing position, in phase 3 in the standing and holding the standing position, and in phase 4 in the seated and holding the sitting position. Systolic blood pressure, mean arterial pressure, and diastolic blood pressure were obtained in each phase. A paired t-test was used to compare the improved and invariant groups before and after treatment. The post-treatment comparison between the improved group and the invariant group was performed by unpaired t-test. Variation of the evaluation index over time was evaluated by repeated measures ANOVA. Multiple comparisons were corrected by the Bonferroni method. Results The EAT showed that parasympathetic activity was significantly suppressed in the improvement group, while the AS test showed significant fluctuations over time for the improvement and invariant groups. The interaction between the time course and the two factors in the improvement and invariant groups was not statistically evident. Although no significant difference was found, the improvement group showed a tendency to suppress parasympathetic activity and a tendency to stimulate sympathetic activity compared to the invariant group. Blood pressure in the improvement group showed a tendency to decrease. Conclusions EAT was found to suppress parasympathetic activity over time, and the AS test did not reveal an interaction effect of EAT on BR. However, there was a trend toward suppression of parasympathetic activity and stimulation of sympathetic activity in the improved group compared to the invariant group. Blood pressure in the improved group tended to decrease. It is possible that EAT may have a positive effect on autonomic neuropathy symptoms such as orthostatic dysregulation (OD), postural orthostatic tachycardia syndrome (POTS), etc. by stimulating the BRs. It is thought that the autonomic nervous system stimulating action and the immune system stimulating action act synergistically to express the therapeutic effect of EAT.

Orthostatic hypotension in dementia with Lewy bodies: a meta-analysis of prospective studies.

PURPOSE: Orthostatic hypotension (OH), one of the supportive clinical features in the diagnosis of dementia with Lewy bodies (DLB), is a significant problem in advanced age because of its severe negative consequences. The aim of this meta-analysis was to investigate the prevalence and risk of OH in patients with DLB. METHODS: The indexes and databases cited to identify relevant studies were PubMed, ScienceDirect, Cochrane, and Web of Science. The keywords for the search were "Lewy body dementia" and "autonomic dysfunction" or "dysautonomia" or "postural hypotension" or "orthostatic hypotension." English-language articles published from January 1990 to April 2022 were searched. The Newcastle-Ottawa scale was applied to evaluate the quality of the studies. Odds ratios (OR) and risk ratios (RR) were extracted with 95% confidence intervals (CI) and combined using the random effects model after logarithmic transformation. The prevalence in the patients with DLB was also combined using the random effects model. RESULTS: Eighteen studies (10 case controls and 8 case series) were included to evaluate the prevalence of OH in patients with DLB. Higher rates of OH were found to be associated with DLB (OR 7.71, 95% CI 4.42, 13.44; p < 0.001), and 50.8% of 662 patients had OH. CONCLUSION: DLB increased the risk of OH by 3.62- to 7.71-fold compared to healthy controls. Therefore, it will be useful to evaluate postural blood pressure changes in the follow-up and treatment of patients with DLB.

The differences of orthostatic hypotension in patients with Parkinson's disease and multiple system atrophy.

Background: Multiple system atrophy (MSA) and Parkinson's disease (PD) have similar clinical presentations in their early stages. Orthostatic hypotension (OH) is a common autonomic dysfunction associated with MSA and PD. Heart rate (HR) and systolic blood pressure (SBP) changes are measured in response to the active standing test, which is widely used to screen for cardiovascular autonomic function. Objectives and methods: Overall, 255 patients (67 MSA, 188 PD) underwent continuous beat-to-beat non-invasive BP monitoring and active standing test. The total standing time was 10 min, and the BP differences between both groups were compared to determine whether the ΔHR/ΔSBP can differentiate both conditions. Results: Classical orthostatic hypotension (COH) (52%) and initial OH (19%) were most common in MSA and PD, respectively. MSA had a higher HR (75.0 ± 9.7 vs. 71.0 ± 10.7, P = 0.008) than PD in the supine position. SBP (135.70 ± 15.68 mmHg vs. 127.31 ± 15.14 mmHg, P = 0.106), diastolic BP (78.45 ± 12.36 mmHg vs. 67.15 ± 13.39 mmHg, P = 0.009) and HR (73.94 ± 8.39 bpm vs. 71.08 ± 13.52 bpm, P = 0.389) at baseline were higher in MSA-COH than in PD-COH. After adjusting for age and disease duration, the ΔHR/ΔSBP-10 min significantly discriminated MSA-COH from PD-COH (P = 0.031). An ΔHR/ΔSBP-10 min of 0.517 showed a sensitivity of 67% and specificity of 84% (AUC = 0.77, 95% CI: 0.63-0.91). Conclusion: The SBP, diastolic BP, and HR were higher in the supine position; however, ΔHR and ΔSBP were lower after standing in MSA patients than in PD patients. The ΔHR/ΔSBP-10 min discriminated between MSA-COH and PD-COH with quiet acceptable accuracy.

The baroreceptor reflex brought to life outside the classroom - an e-learning based asynchronous laboratory class using a non-supervised modified Active Standing Test.

BACKGROUND: E-learning based laboratory classes can replace or enhance in-classroom laboratories. They typically offer temporal flexibility, self-determined learning speed, repeatability and do not require supervision or face-to-face contact. The aim of this feasibility study was to investigate whether the established in-classroom laboratory class on the baroreceptor reflex (BRR) can be transformed into a new e-learning based asynchronous laboratory class for untrained, non-supervised students without medical equipment. The BRR is a fundamental cardiovascular process which is regularly visualized in physiology during in-classroom laboratories by a student-performed Active Standing Test (AST). During this voluntary provocation of orthostatic stress, the BRR reliably causes a solid rise in heart rate (HR) and a stabilization or even increase in blood pressure (BP). METHODS: The conventional AST was modified by omission of BP measurements which would require medical devices and was embedded into a framework of interactive digital material allowing independent student performance. With specific adaptions, this instrument was implemented to 1st and 2nd year curricula of human medicine, dental medicine, midwifery and pharmacy. An audience response system was used to collect the students' data on HR, epidemiology, technical problems, satisfaction and orthostatic symptoms. As primary outcome, we investigated the students' correct performance of the modified AST regarding textbook conformity of the HR data. Secondary outcomes included technical feasibility, the students' satisfaction and consistency of HR data within predefined subgroups (e.g., gender, curricula). Descriptive statistics are reported. RESULTS: The class was completed by 217 students (mean age: 23 ± 8 [SD], 81% female, 19% male). Mean reported rise of HR during standing was ~ 20 bpm (~ 30%) which is highly concordant to textbooks. Reported feasibility (~ 80% negated any technical issues) and students' satisfaction (4.4 on 5-point Likert-scale) were high. The HR data were consistent within the subgroups. CONCLUSION: This study demonstrates that the highly relevant BRR can be successfully addressed in an e-learning based asynchronous laboratory class implementing a non-supervised AST restricted to HR measurements embedded in digital material. The robust HR response and the adjustable complexity allow an application to different healthcare-related curricula. This class, therefore, provides a broad audience access to a fundamental concept of cardiovascular physiology.

Skin sympathetic nerve activity in patients with chronic orthostatic intolerance.

BACKGROUND: Chronic orthostatic intolerance (OI) is characterized by the development of tachycardia and other symptoms when assuming an upright body position. OBJECTIVE: The purpose of this study was to test the hypothesis that skin sympathetic nerve activity (SKNA) bursts are specific symptomatic biomarkers in patients with chronic OI. METHODS: We used an electrocardiogram monitor with a built-in triaxial accelerometer to simultaneously record SKNA and posture in ambulatory participants. Study 1 compared chronic OI (14 women and 2 men; mean age 35 ± 10 years) with reference control participants (14 women; mean age 31 ± 6 years). Study 2 included 17 participants with chronic OI (15 women and 2 men; mean age 39 ± 12 years) not yet treated with ivabradine, pyridostigmine, or ß-blockers. RESULTS: In study 1, there were 124 episodes (8 ± 4 per participant) of postural changes, with 11 episodes (8.9%) associated with symptoms. In comparison, 0 of 104 postural changes (7 ± 3 per participant) in controls were symptomatic (P = .0011). In participants with chronic OI, the SKNA bursts associated with symptoms had higher burst frequencies, longer burst durations, and larger mean burst areas than did bursts during asymptomatic periods. However, SKNA bursts and tachycardia were asymptomatic in controls. We analyzed 110 symptomatic episodes in study 2 (6 ± 5 per participant). Among them, 98 (89.1%) followed at least 1 SKNA burst. In comparison, only 41 (37.3%) had heart rate exceed 100 beats/min 1 minute before symptom onset (P < .0001). CONCLUSION: SKNA bursts are a highly specific, albeit insensitive, symptomatic biomarker for chronic OI.

Orthostatic Headache in Children Including Postural Tachycardia Syndrome and Orthostatic Hypotension: A Near-Infrared Spectroscopy Study.

BACKGROUND AND AIM: Although head and/or neck pain attributed to orthostatic hypotension is included in international guidelines, its mechanisms and relevance remain unknown. This study examined the term's relevance and aimed to elucidate the associated clinical features. METHODS: An active stand test was performed to evaluate fluctuations in systemic and cerebral circulation in children and adolescents reporting complaints in the absence of a confirmed organic disorder. The subjects were categorized based on orthostatic headache presence/absence, and their characteristics and test results were compared. RESULTS: Postural tachycardia syndrome was observed in 50.0% of children with, and 55.1% without, orthostatic headache. For orthostatic hypotension, the respective values were 31.3% and 30.6%. A history of migraine was more prevalent in children with orthostatic headaches (64.1% vs. 28.6%; p < 0.01). The observed decrease in the cerebral oxygenated hemoglobin level was larger in children with orthostatic headaches (Left: 6.3 (3.2-9.4) vs. 4.1 (0.8-6.1); p < 0.01, Right: 5.3 (3.1-8.6) vs. 4.0 (0.8-5.9); p < 0.01). CONCLUSION: Fluctuations in cerebral blood flow were associated with orthostatic headaches in children, suggesting that the headaches are due to impaired intracranial homeostasis. As orthostatic headache can have multiple causes, the term "head and/or neck pain attributed to orthostatic (postural) hypotension" should be replaced with a more inclusive term.

Cerebral Blood Oxygenation Changes in Juvenile Patients with Delayed Orthostatic Hypotension During an Active Standing Test.

Delayed orthostatic hypotension (OH) is a minor subset of orthostatic dysregulation (OD). Cerebral blood oxygenation in juvenile patients with delayed OH has not been studied. We investigated the bilateral changes in cerebral oxygenation in the prefrontal cortex during an active standing test in 23 juvenile patients with delayed OH using near-infrared spectroscopy (NIRS). We measured the oxy-Hb, deoxy-Hb, and total-Hb during the active standing test. Four observations were made during the test: t1 in a resting supine position, t2 when maintaining blood pressure, and the remaining two (t3, t4) during hypotension. The concentration of oxy-Hb significantly decreased prior to satisfying the diagnostic criteria of delayed OH after standing and did not change thereafter. The concentration of deoxy-Hb increased gradually during the measurement periods. In addition, total-Hb increased from t2 to t3. There was no significant difference in the change in each Hb parameter between the left and right cerebral hemispheres. Our results indicate that NIRS parameters are more sensitive than blood pressure for the interpretation of cerebral autoregulation in juvenile patients with delayed OH.

Autonomic nervous system function in adolescent migraineurs.

BACKGROUND: Migraine is a common and disabling neurological disorder. Studies on the relationship between migraine and the autonomic nervous system (ANS) have been inconclusive. Moreover, pediatric studies are extremely limited. Therefore, the present study investigated interictal ANS function in adolescent migraineurs. METHODS: We studied 21 patients with migraine and 26 healthy controls. Beat-to-beat blood pressure (BP) and heart rate (HR) were non-invasively and continuously measured in the supine and standing positions. ANS function was evaluated on power spectral analysis of HR variability and diastolic BP (DBP) variability. RESULTS: Heart rate and systolic BP were not different between the two groups in either the supine or standing position. DBP did not differ between groups in the standing position, but was significantly higher in migraineurs in the supine position. The vasoconstrictor index was significantly higher in migraineurs. High-frequency (HF) RR interval variability (RR-HF) and the ratio of the low-frequency (LF) to HF component of RR interval variability (RR-LF/HF) were not different between the two groups in both positions. The LF component of DBP variability (DBP-LF) in the supine position was significantly lower in migraineurs, while DBP-LF during standing in migraineurs was significantly higher than in controls. CONCLUSION: Migraineurs have significantly lower sympathetic vasomotor activity in the supine position, while sympathetic vasomotor activity was hyperresponsive during standing.

Which is preferable for orthostatic hypotension diagnosis in older adults: active standing test or head-up tilt table test?

BACKGROUND: Correct evaluation of orthostatic hypotension (OH) is crucial in geriatric practice, since OH is associated with mortality and morbidity. The study aimed to determine the most appropriate method for measuring blood pressure in transition from supine to upright position in order to diagnose OH in older adults. METHODS: Active standing test (AST) and head-up tilt table (HUT) test as well as comprehensive geriatric assessment (CGA), including mini-mental state examination or the cognitive state test, mini-nutritional assessment, basic and instrumental activities of daily living, and Tinetti performance-oriented mobility assessment indexes, were performed in 290 geriatric patients. RESULTS: The prevalence of OH during HUT and AST was 19% and 37%, respectively. In patients with OH during HUT, the frequency of dementia and recurrent falls were higher (P<0.05); on the other hand, the levels of serum vitamin D and albumin and estimated glomerular filtration rate were lower (P<0.05). However, all these parameters for OH during AST were not significant (P>0.05). Comparison of the groups according to CGA measurements revealed significant differences in terms of cognition, nutritional status, activities of daily life, and balance function in patients with OH only during HUT (P<0.05), but not during AST (P>0.05). The sensitivity, specificity, positive predictive value, and negative predictive values of AST were 49.0%, 65.5%, 25.0%, and 84.6% respectively, according to HUT. CONCLUSION: The results suggest that orthostatic blood pressure changes determined by HUT might be of higher clinical significance than that by AST in older adults. It might be important that the evaluation of OH by HUT should be included in daily geriatric practice.