Clinical Autonomic Research最新文献

Purpose: Establish the minimally clinically important difference (MCID) for the Orthostatic Hypotension Questionnaire (OHQ).

Background: Neurogenic orthostatic hypotension (nOH) causes disabling symptoms that impair daily function and quality of life. The OHQ is a validated patient-reported outcome with a symptom assessment (OHSA) and daily activity scale (OHDAS), widely used in clinical trials, despite the MCID being unestablished.

Methods: We analyzed data from two phase 3, randomized placebo-controlled trials (SEQUOIA and REDWOOD), evaluating ampreloxetine for symptomatic nOH in patients with Parkinson disease, multiple system atrophy, and pure autonomic failure. Using anchor-based and distribution-based methods, we calculated the MCID for the total OHQ score, OHSA and OHDAS composite subscales, and for the single dizziness/lightheadedness question (OHSA1).

Results: The analysis included 184 subjects from SEQUOIA and 128 from REDWOOD. The total OHQ MCID for improvement was a reduction of 0.9-1.2 points and for worsening was an increase of 0.7-1.1 points. The MCID for the OHSA composite ranged from a reduction of 0.9-1.3 points for improvement and an increase of 0.7-1.1 points for worsening. For the single-item OHSA1, the MCID was a reduction of 2.0-3.0 points for improvement and an increase of 1.0 point for worsening. Owing to poor correlation with the symptom-based anchors, a reliable MCID for the OHDAS component was not established.

Conclusions: These MCID thresholds for the OHQ, OHSA and OHSA item 1 alone, enhance the interpretability of scores and support their use in evaluating clinical benefit.

Background and objective: The association between blood pressure variability (BPV) or heart rate variability (HRV) and the baroreflex is well established. However, the role of the vestibular-autonomic reflex in regulating BP and HR stability has primarily been explored only in experimental studies. We aimed to delineate the association of BPV and HRV with otolith function in postural orthostatic tachycardia syndrome (POTS).

Methods: We retrospectively analyzed data from consecutive patients with POTS recruited between April 2021 and April 2025 at a tertiary referral-based hospital in South Korea. All patients underwent a head-up tilt table test using a Finometer^® device and cervical (cVEMP) and ocular vestibular evoked-myogenic potentials (oVEMP). The Finometer data were analyzed using a power spectral analysis. The Finometer, cVEMP, and oVEMP data were compared with those of 32 age- and sex-matched healthy participants.

Results: A total of 47 patients with POTS (mean age $\pm$ standard deviation [SD] = 33 $\pm$ 10 years; 30 female patients) and 32 age- and sex-matched healthy participants were included for analysis. The n1-p1 amplitude of oVEMP was larger in patients with POTS than in healthy participants (p = 0.002). p13 latency was negatively correlated with the SD of heart rate in the supine position in patients with POTS (p = 0.001), a trend not observed in healthy participants. The n1-p1 amplitude (odds ratio [95% confidence interval] = 1.27 [1.08-1.49], p = 0.004) and root mean square of successive differences (RMSSD) during tilting (0.82 [0.72-0.93], p = 0.001) were associated with POTS after adjusting for other covariates.

Conclusions: Otolithic function may play a role in accentuating BPV and HRV in POTS by contributing to enhanced sympathetic outflow.

Purpose: Spontaneous indices have been widely used to assess baroreflex gain despite their numerous limitations and concerns regarding their validity, reliability, and reproducibility. In this retrospective study, we investigated whether spontaneous baroreflex indices reflect cardiovagal baroreflex gain assessed by the neck-chamber technique in those with spinal cord injury (SCI) and in uninjured individuals. SCI represents a model of preserved cardiovagal baroreflex control coupled with impaired sympathetic effects on the vasculature.

Methods: We derived three spontaneous indices of baroreflex sensitivity (sequence method, low-frequency (LF), and high-frequency (HF) transfer function) and compared them with baroreflex gain obtained via the neck-chamber technique in adults with SCI (n = 29; neurological level C1-T10, ≤ 2 years since injury) and uninjured adults (n = 14).

Results: In both groups, spontaneous indices were highly correlated with each other (all p < 0.01). In uninjured participants, neck suction baroreflex gain did not relate to any spontaneous index. In individuals with SCI, neck-chamber gain correlated significantly with spontaneous indices (all r > 0.43, p < 0.05); these relationships were significantly stronger in individuals with neurologically complete injuries (sequence: r = 0.67, p < 0.01; LF: r = 0.79, p < 0.001; HF: r = 0.76, p < 0.001). However, Bland-Altman analysis revealed a strong proportional bias, with spontaneous indices consistently and progressively overestimating neck-chamber gain (all r > 0.91, p < 0.001).

Conclusions: These results suggest that sympathetic activity is largely responsible for the lack of correspondence between spontaneous and neck-chamber baroreflex gains. However, even in individuals with a neurologically complete SCI, where sympathetic influences are minimal, spontaneous indices may not consistently reflect baroreflex gain derived from other methods.

Purpose: Cardiovascular autonomic failure and neurogenic orthostatic hypotension (nOH) are common and disabling in Parkinson's disease (PD) and multiple system atrophy (MSA). Recent studies have shown evidence of postganglionic autonomic denervation in MSA as well as PD. We aimed to characterise the relationship between nOH, autonomic failure and postganglionic denervation in PD and MSA. We hypothesised that postganglionic autonomic denervation contributes to the development of nOH and correlates with the severity of cardiovascular autonomic failure.

Methods: We assessed 57 patients (37 PD, 20 MSA, median 64 [IQR 59-70] years) with cardiovascular autonomic testing; dynamic sweat testing; plasma noradrenaline levels; skin biopsies for quantification of intraepidermal, pilomotor and sudomotor innervation; and autonomic symptom questionnaires.

Results: Overall, 78% of patients with MSA and 36% with PD had nOH ≥ 20/10 mmHg. The MSA group had more severe nOH, sudomotor dysfunction and cutaneous denervation, with higher supine noradrenaline than the PD group. Only supine noradrenaline differed between MSA and PD with nOH subgroups (P = 0.04). Overall, patients with nOH demonstrated more severe (1) cardiovascular autonomic failure, with reduced pressor responses to isometric exercise, deep breathing and Valsalva ratio; (2) intraepidermal, pilomotor and sudomotor denervation; and (3) autonomic symptoms and Hoehn-Yahr grade. The severity of nOH and cardiovascular autonomic failure correlated with autonomic denervation, patient symptoms and Hoehn-Yahr grade (ρ ≥ 0.50).

Conclusions: nOH was associated with cutaneous autonomic denervation in both PD and MSA, with correlations between cardiovascular autonomic failure, cutaneous denervation and Hoehn-Yahr grade. Postganglionic autonomic denervation may contribute to nOH in PD and MSA, and affect responses to therapeutic agents.

Background: Orthostatic hypotension (OH) is prevalent in older adults and is often associated with falls. However, the presence or absence of symptoms in OH may be mediated by cerebral autoregulation, which helps maintain cerebral perfusion during blood pressure fluctuations.

Methods: We recruited 40 older adults (aged ≥ 55 years) from the Malaysian Elders Longitudinal Research (MELoR) cohort. Participants underwent cerebral blood flow velocity monitoring using transcranial Doppler ultrasonography and beat-to-beat blood pressure recording. Three protocols were used: active stand, mental arithmetic, and Valsalva manoeuvre. Participants were categorized, based on OH (≥ 30 mmHg systolic drop) and fall history, into four groups. Cerebrovascular resistance (CVR) was derived and analysed.

Results: Participants with OH but no history of falls demonstrated preserved autoregulatory responses, as reflected by adaptive reductions in CVR. In contrast, fallers-regardless of OH status-had impaired CVR modulation. Significant group differences were found during the active stand test at 165 s and 180 s (p < 0.05).

Conclusion: Preserved cerebral autoregulation may protect older adults with OH from symptomatic manifestations such as falls. Targeting cerebral autoregulation could offer novel approaches for preventing falls in this population.