Severity Of Orthostatic Hypotension Research Articles

Augmentation with prazosin for patients with depression and a history of trauma: A randomised, double-blind, placebo-controlled study.

Depression with a history of trauma often responds poorly to conventional antidepressants and has a poor prognosis. Prazosin, an α1-adrenoceptor blocker, has shown promise in treating post-traumatic stress disorder symptoms, particularly nightmares. Its potential in treating depression with trauma history warrants investigation. This randomised, double-blind, placebo-controlled study aimed to investigate the efficacy and tolerability of low-dose prazosin (0.5-1 mg/day) as an augmentation strategy in patients with depression and a history of trauma. We sought to determine if prazosin could provide rapid symptom improvement and enhance overall treatment response compared to placebo in this difficult-to-treat patient population. This randomised, double-blind, placebo-controlled clinical study included 59 patients with first-episode or recurrent unipolar or bipolar depression. After basic antidepressant treatment, they were randomly assigned to a prazosin (0.5-1 mg/day) or placebo group for a 6-week double-blind controlled study. The Montgomery-Åsberg Depression Rating Scale, 17-item Hamilton Depression Scale (HAMD-17), and Hamilton Anxiety Scale (HAMA) were used to evaluate efficacy. There were no significant differences in the results of the demographic and clinical symptom assessment between the two groups (p > 0.05). The difference between the HAMD-17 and HAMA scores was statistically significant after 3 days of treatment (p < 0.05). The difference in response rate between the two groups was statistically significant after week 4 of treatment (end of week 4, 56.7% vs. 24.1%, p = 0.011; end of week 6, 80.0% vs. 48.3%, p = 0.011). The incidence of adverse reactions in the prazosin and placebo groups was 20.0% and 24.1%, respectively, with no statistically significant differences (p > 0.05); however, the prazosin group had a lower incidence of sleeplessness or nightmares (3.3% vs. 20.7%, p = 0.039) but a higher incidence of orthostatic hypotension (16.7% vs. 0%, p = 0.007). The severity of orthostatic hypotension was mild to moderate. Low-dose prazosin can effectively improve the emotional symptoms of patients with depression and a history of trauma, and the common adverse reaction is mild-to-moderate orthostatic hypotension. ChiCTR2200063642.

Abnormal brain-heart electrophysiology in mild and severe orthostatic hypotension.

This study investigated the changes in cardiocerebral electrophysiology in patients with mild orthostatic hypotension (MOH) and severe orthostatic hypotension (SOH) and their relationship with the severity of orthostatic hypotension, psychiatric symptoms, and cognitive dysfunction. This study included 72 nonorthostatic hypotension (NOH), 17 with MOH, and 11 with SOH. Seated resting-state heart rate variability (HRV) and quantitative electroencephalogram parameters were synchronized and recorded. HRV measures in the time and frequency domains were analyzed, along with the peak frequency and power of the brain waves. Abnormal neuronal activity was found in FP1 in patients with MOH, whereas it was more widespread in FP1, FP2, and O2 in patients with SOH ( P < 0.05). Cardiac and cerebral electrophysiological abnormalities were significantly associated with orthostatic hypotension severity, psychiatric symptoms, and cognitive dysfunction. Abnormal EEG activity in patients are mainly manifested in the prefrontal and occipital lobes, especially in patients with SOH. These results may help patients to better understand the mechanisms underlying orthostatic hypotension severity and psychiatric and cognitive impairment in orthostatic hypotension.

Effect of RNAi therapeutics patisiran and vutrisiran on orthostatic hypotension due to dysautonomia in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy

Abstract Background Hereditary transthyretin-mediated (hATTR) amyloidosis, also known as ATTRv amyloidosis, is a rapidly progressive, multisystem disease. Orthostatic hypotension, due to autonomic neuropathy, is a common yet hard-to-treat disease manifestation in patients with hATTR amyloidosis. Fatigue, muscle weakness, and deterioration in cardiac function further exacerbate orthostatic symptoms. Efficacy of RNAi therapeutics patisiran and vutrisiran was assessed in patients with hATTR amyloidosis with polyneuropathy across the APOLLO (NCT01960348), Global Open-Label Extension (OLE) (NCT02510261), and HELIOS-A (NCT03759379) studies, respectively. Purpose Evaluate the quantitative effect of patisiran and vutrisiran on orthostatic hypotension in patients with hATTR amyloidosis with polyneuropathy. Methods In APOLLO, patients were randomised 2:1 to patisiran 0.3 mg/kg or placebo, IV q3w. Patients who completed APOLLO (APOLLO-placebo, APOLLO-patisiran) were eligible to enrol into the ongoing Global OLE (patisiran 0.3 mg/kg IV q3w). In HELIOS-A, patients were randomised 3:1 to vutrisiran (25 mg SC q3m) or patisiran (0.3 mg/kg IV q3w; reference group). Primary endpoint for APOLLO and HELIOS-A was change from baseline in the modified Neuropathy Impairment Score+7 (mNIS+7) vs APOLLO placebo at M18 (APOLLO) and M9 (HELIOS-A). Orthostatic hypotension was evaluated using the postural blood pressure (PBP) component of mNIS+7, calculated as the mean of 2 supine readings of systolic BP [SBP, mmHg] taken 15 min apart minus the lowest SBP upon standing at 1, 3, and 5 min. A smaller reduction in observed SBP between supine and upright readings indicated an improved PBP. Results APOLLO enrolled 225 patients (placebo, n=77; patisiran, n=148), Global OLE 211 and HELIOS-A 164 (vutrisiran, n=122; patisiran, n=42). At baseline, the severity of orthostatic hypotension was similar between within-study treatment arms in APOLLO and HELIOS-A. In APOLLO, patisiran-treated patients showed PBP improvement or stabilization from baseline to M18 (mean [SD] change in SBP: baseline, −17.6 [19.4]; M18, −13.5 [16.8]) and was maintained at Global OLE 36m (−13.4 [15.6]). In contrast, placebo-treated patients in APOLLO had an increased change in PBP over 18m (baseline, −17.5 [16.5]; M18, −20.4 [16.9]); their PBP improved after patisiran initiation (Global OLE 36m, −16.6 [18.1]). In HELIOS-A, stabilization in PBP was observed in the vutrisiran arm (baseline, −11.2 [14.0], M18, −11.7 [14.6]). In the smaller patisiran arm, while the change in PBP increased, the value remained in the normal range (baseline, −11.6 [17.2]; M18, −14.2 [15.5]). Patisiran and vutrisiran have acceptable safety profiles. Conclusions PBP analyses quantify the benefits of RNAi therapeutics patisiran and vutrisiran on autonomic function in patients with hATTR amyloidosis with polyneuropathy. The increase in change in PBP to a symptomatic range without treatment indicates the importance of early intervention. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Alnylam Pharmaceuticals

Orthostatic Hypotension Management in Patients with Traumatic Cervical Myelopathy

Aim. To study the incidence and severity of orthostatic hypotension and develop a method for its correction in patients after spinal cord injury (SCI) at the cervical level. Material and мethods. The study included 120 patients after spinal cord injury at cervical level with tetraplegia C5–C8 motor levels since injury more than 1 year divided into 3 groups comparable in terms of demographic, neurological and functional parameters. The group 1 (control) received standard therapy (exercise therapy, modalities, ergotherapy, massage), the group 2 received standard therapy and permanent wearing of an abdominal bandage during the day, the group 3 received rehabilitation identical to the group 2 in conjunction with low-intensity laser therapy (reflex-segmental technique). Evaluation of the results was carried out at the beginning (T1), at the end (T2) after a 30-day rehabilitation course; in assessing the state of the ANS used heart rate variability, ABPM, tilt test, deep breathing test; the motor system was assessed using the international neurological assessment standard — ASIA Impairment Scale, the FIM motor subscale (FIMm). Results and discussion. The quantity of 35% of patients have orthostatic hypotension while subjective manifestations during the tilt test was seen only in 22% of patients. At the initial examination, there were no differences between the groups in terms of vegetative and functional status. There were no changes in neurological status in all groups, functional activity increased by 6 ± 5.4 points in the control group (FIMm), and 6 ± 4.6 and 7 ± 4.5 points in 2 and 3 groups, respectively without any the statistical differences between the groups (F = 0.51; p = 0.42) at the end of rehabilitation. There were positive changes in vegetative parameters in all groups, with the exception of the mean night systolic blood pressure (SBP) between the 1 and 2 groups. Intergroup comparison have shown positive changes in all vegetative parameters that was higher in the 2 and 3 groups: decreasing drop of SBP during tilt test was 4 ± 2.8. and 5 ± 3.2 mm Hg, increase in inspiratory- expiratory index (RRmax / RRmin) 0.5 ± 0.08 and 0.7 ± 0.10 units, increase in daytime mean SBP (ABPM) 5 ± 1.1 and 8 ± 1.4 mm Hg respectively in groups 2 and 3, against 2 ± 1.9 mm Hg. and 0.2 ± 0.05 units, 3 ± 0.9 mm Hg in the group 1. In group 3, the value and increase in RRmax / RRmin (1.21 ± 0.11; 1.23 ± 0.13; 1.27 ± 0.15, respectively, in 1, 2 and 3 groups), mean daytime SBP (105 ± 3; 108 ± 3; 110 ± 4 mm Hg, respectively in 1, 2, and 3 groups) was higher in the group 3. Conclusion. Orthostatic Hypotension (OH) occured in one third of patients in the late period after SCI at the cervical level, the method of OH management that included daytime abdominal bandage wearing and using low-intensity laser radiation (905 nm, 50 Hz) on the cardioreflex zones has shown its preliminary effectiveness.

Effect of Nursing Interventions on the Severity of Orthostatic Hypotension among Older Adults Residing in Assisted Living Facilities

Effect of Nursing Interventions on the Severity of Orthostatic Hypotension among Older Adults Residing in Assisted Living Facilities

Impact of depressive symptoms on self-perceived severity of autonomic dysfunction in multiple system atrophy: relevance for patient-reported outcomes in clinical trials.

To assess the relationship between depressive symptoms and self-perceived severity of autonomic dysfunction in patients with multiple system atrophy (MSA). Cross-sectional evaluation of patients with MSA who underwent autonomic testing, Unified MSA Rating Scale (UMSARS)-1 and -2, rating of the presence and severity of depressive symptoms (Zung scale), quality of life (SF-36), body vigilance, anxiety (Spielberger's anxiety scale), severity of autonomic dysfunction with the Composite Autonomic Symptoms Score (COMPASS-31), and severity of orthostatic hypotension (OH) symptoms with the Orthostatic Hypotension Questionnaire (OHQ). Fifty-eight patients (32 women) with probable MSA (aged 61.8 ± 8.6years; disease duration 4.3 ± 2.1years) were studied. Forty patients (69%) had symptoms of depression in the Zung scale. Age, disease duration, and motor disability were similar in those with and without symptoms of depression. Despite a similar orthostatic blood pressure fall, the severity of orthostatic symptoms was higher in patients with symptoms of depression (p = 0.004). Depression scores were associated with higher burden of autonomic symptoms (R = 0.401, p = 0.02), specifically with the COMPASS-31 items related to orthostatic intolerance (R = 0.337, p = 0.045), and with the OHQ (R = 0.529; p < 0.001). A multivariable regression model including age, sex, UMSARS, and drop in systolic blood pressure upon head-up tilt as covariates showed that the burden of depressive symptoms was independently associated with the OHQ score: for every 1-unit increase in the Zung depression score, there was a 1.181-point increase in the total OHQ score. In patients with MSA, depressive symptoms worsen the perceived severity of autonomic symptoms in general and orthostatic hypotension in particular. Our findings have implications for clinical trial design.

Disease progression and prognostic factors in multiple system atrophy: A prospective cohort study

Multiple system atrophy (MSA) is a rare neurodegenerative disease, with limited understanding of disease progression and prognostic factors. We leveraged the data of a large prospective cohort of MSA to study both clinical progression and survival and assess their determinants. All consecutive patients seen at the French Reference Centre for MSA since 2007 were included in a prospective cohort with an annual follow-up including the Unified MSA Rating Scale (UMSARS). We used joint models to evaluate the risk of death, the mean trajectory of each UMSARS subscale and to determine the potential factors. Investigated factors included gender, age at baseline, MSA subtype, diagnosis certainty, type of first symptoms and the duration between symptom onset and the first visit. Among the 261 MSA patients included in our cohort, the median duration of clinical follow-up was 2.1 years (up to 10.3 years) and the median survival was 4.0 years since the first visit. Main factors for poor survival were the progression over time of UMSARS score (I + II and IV) and the severity of orthostatic hypotension. MSA subtype had no effect on progression or survival. The UMSARS I + II score progressed faster over time in subjects with autonomic dysfunction as the initial feature and in women. Despite a faster progression, women and men had similar survival. From this large MSA cohort, we confirm the rapid progression and poor prognosis of MSA. We provide additional evidence for a negative impact of early autonomic dysfunction and the severity of orthostatic hypotension on both disease progression and survival.

A12584 Atherosclerosis of the carotid bulb is associated with severity of orthostatic hypotension along with baroreceptor dysfunction especially in older patients and patients with severe atherosclerosis

A12584 Atherosclerosis of the carotid bulb is associated with severity of orthostatic hypotension along with baroreceptor dysfunction especially in older patients and patients with severe atherosclerosis

Atherosclerosis of the carotid bulb is associated with the severity of orthostatic hypotension in non-diabetic adult patients: a cross-sectional study

ABSTRACTBackground: The carotid bulb has a high density of baroreceptors that play an important role in maintaining blood pressure. We hypothesized that atherosclerosis of the carotid bulb would reflect the severity of orthostatic hypotension more accurately than would atherosclerosis of other carotid artery segments.Methods: This cross-sectional study included 198 non-diabetic adults. We measured the cardio-vascular ankle index as an index of arterial stiffness, intima-media thickness in each carotid artery segment (internal carotid artery, carotid bulb, distal and proximal portions, respectively, of the common carotid artery) as a measure of atherosclerosis, and heart rate variability as a measure of cardiac autonomic function. The sit-to-stand test was used to assess severity of orthostatic hypotension.Results: Intima-media thickness of the carotid bulb was correlated with orthostatic systolic blood pressure change (r = −0.218, p = 0.002), cardio-ankle vascular index (r = 0.365, p < 0.001) and heart rate variability parameters. Multivariate regression analysis revealed that among all of the segments, only intima-media thickness of the carotid bulb was an independent predictor of orthostatic systolic blood pressure change (p = 0.022).Conclusion: Atherosclerosis of the carotid bulb was associated with severity of orthostatic hypotension, arterial stiffening and cardiac autonomic dysfunction than that of other carotid artery segments.

Severity of orthostatic hypotension in the stages of Parkinson’s disease

Severity of orthostatic hypotension in the stages of Parkinson’s disease

Abstract P492: Lower Body Mass Index is Associated With Arterial Stiffening and Severity of Orthostatic Hypotension in Middle-aged and Older Patients With Abdominal Obesity

Background: Recently, patients with both sarcopenia and abdominal obesity are known to exhibit subclinical atherosclerosis and high mortality risk. Sarcopenic obesity is considered to be latent in those without increase in body mass index (BMI) despite having abdominal obesity. We aimed to investigate whether arterial stiffening and severity of orthostatic hypotension, which is the risk of cardiovascular disease, is associated with lower BMI in patients with abdominal obesity. Methods: We studied middle-aged and older patients with normal to high BMI (BMI ≥ 18.5) and being treated with life-style related diseases. The patients were divided into 2 groups (with or without abdominal obesity) according to waist circumference (WC) (abdominal obesity: men; WC ≥ 85 cm, women; WC ≥ 90 cm). We measured cardio-vascular ankle index (CAVI) for an index of arterial stiffness. We assessed sit-to-stand test for measuring orthostatic systolic blood pressure (SBP) change. Results: One thousand and forty-six patients were included in the study. Mean age of the patients was 68.0 ± 10.1 years (42.5% were men), hypertension dyslipidemia and diabetes mellitus was observed in 83.3%, 74.3% and 20.2% of the patients respectively. There was a significant negative correlation with BMI and CAVI in patients with abdominal obesity (r=-0.309, p&lt;0.001, n=434), whereas no significant association was observed in patients without abdominal obesity (p=N.S., n=612). There was a significant positive correlation with BMI and orthostatic SBP change in patients with abdominal obesity (r=0.213, p&lt;0.001) and in patients without abdominal obesity (r=0.117, P=0.004). Multivariate regression analysis revealed that BMI was an independent determinant of CAVI and orthostatic SBP change in patients with abdominal obesity (p&lt;0.001, p&lt;0.001, respectively), and was an independent determinant of orthostatic SBP change in patients without abdominal obesity (p=0.004). Conclusion: In patients with abdominal obesity, lower BMI was an independent determinant of arterial stiffening and severity of orthostatic hypotension. Further investigation by evaluating body composition is necessary and now ongoing to assess the risk of lower BMI in patients with abdominal obesity.

Severity of orthostatic hypotension in the course of Parkinson's disease: no correlation with the duration of the disease.

Orthostatic hypotension (OH) is a common issue in Parkinson's disease (PD), affecting about 30%-40% of PD patients. Symptoms of OH include lightheadedness, dizziness, postural instability, vertigo and blurred vision. OH considerably contributes to disease burden and reduced quality of life for PD patients. To determine whether the severity of OH in PD advances significantly with the duration of the disease. For 106 PD patients lying-to-standing orthostatic tests were performed to evaluate orthostasis. Severity of OH was measured as maximal drop of systolic blood pressure (SBP) after postural challenge, as the mean of three measurements. The relationship between the maximal drop of SBP and the duration of PD was tested applying ANOVA. Consecutively, 64 patients under regular ambulant supervision received appointments to evaluate their orthostasis repeatedly. From these patients a separate cohort was set up to investigate OH progression in the course of PD. The lack of a correlation between the severity of OH in PD and the duration of the disease was determined (p = 0.064). The long term analysis for the patients under regular ambulant supervision demonstrated that the severity of OH does not advance in the course of PD in a statistically significant manner (p = 0.83). OH does not appear to be a symptom only of the late stage of PD. The presence of OH along with early motor signs does not necessarily point to multiple system atrophy.

Spectral Analyses of Cardiovascular Control in Rodents with Spinal Cord Injury

The severity of injury to cardiovascular autonomic pathways following clinical spinal cord injury (SCI) can be evaluated with spectral analyses. Whether this technique provides a translatable assessment of cardiovascular autonomic function in rodent SCI is unknown. Beat-to-beat blood pressure and pulse interval were measured in male rats 1 month after complete T3 or T10 SCI, and in uninjured control animals. Univariate autoregressive spectral analyses were performed and the power of the low frequency (LF), high frequency (HF), and very low frequency (VLF) peaks identified. Frequency domain variables were correlated with the severity of orthostatic hypotension (OH) and the severity of hypertension during autonomic dysreflexia (AD). Total heart rate variability (HRV) and blood pressure variability (BPV) were reduced in animals with T3, but not T10, SCI. VLF and LF HRV were reduced and HF HRV was increased in animals with T3 SCI compared to controls; there were no changes in animals with T10 SCI. BPV in the VLF and LF range was reduced in animals with T3 SCI, but not T10 SCI. In all animals with SCI, severity of OH was positively correlated with LF BPV, and negatively correlated with HF BPV. Severity of AD was positively correlated with HF BPV and HF HRV, and negatively correlated with VLF HRV. Spectral analyses can detect alterations in cardiovascular autonomic function in animals with SCI at rest. These parameters underscore the distinct cardiovascular ramifications of high- versus low-thoracic SCI, and correlate with the severity of AD and OH, clinically-relevant measures of abnormal blood pressure control.

077 Cerebrovascular autoregulation during orthostatic stress after spinal cord injury

077 Cerebrovascular autoregulation during orthostatic stress after spinal cord injury

Microstructural White Matter Abnormalities of Multiple System Atrophy: In Vivo Topographic Illustration by Using Diffusion-Tensor MR Imaging

To determine whether diffusion-tensor (DT) imaging can demonstrate microstructural white matter abnormalities of multiple system atrophy (MSA) and to correlate these imaging findings with clinical signs and symptoms. Institutional review board approval and written informed consent were obtained. DT imaging was performed in 16 patients with MSA with predominant cerebellar symptoms (MSA-C) (mean age, 60.0 years + or - 5.1 [standard deviation]; range, 51-69 years) and 16 age-matched healthy subjects. Fractional anisotropy (FA) and mean diffusivity (MD) were compared voxel-by-voxel between the two groups by using a two-sample t test. Overlap maps were created to illustrate areas with FA and MD alterations. Correlation between DT imaging indexes and Barthel index score, scale for assessment and rating of ataxia (SARA) score, severity of orthostatic hypotension, age of disease onset, and disease duration was tested by using Spearman rank or Pearson product-moment correlation analysis. T2-weighted and proton density-weighted images of the patients were visually assessed. Widespread areas of FA reduction and MD elevation were observed in supra- and infratentorial white matter structures in patients with MSA (P < .05, false discovery rate corrected). Significant correlation (P < .01) between DT imaging indexes and Barthel index score, SARA score, severity of orthostatic hypotension, and disease duration was observed for multiple areas with FA and/or MD alterations. T2-weighted and proton density-weighted images showed no significant abnormality in supratentorial white matter. DT imaging may help identify the microstructural white matter abnormalities of MSA-C. DT imaging may be useful for severity assessment of MSA-C.

Pupillary autonomic dysfunction in multiple system atrophy and Parkinson’s disease: an assessment by eye-drop tests

To compare pupillary autonomic dysfunction in multiple system atrophy (MSA) and Parkinson's disease (PD). We administered eye-drop tests to 40 MSA patients, 40 PD patients with similar disease duration, and 20 age-matched healthy controls. Pupillary supersensitivity to a parasympathomimetic agent (0.05% pilocarpine hydrochloride) and to a sympathomimetic agent (0.02% dipivefrine hydrochloride) was examined by assessing changes in pupil diameter. Pupillary supersensitivity to a parasympathomimetic agent (0.05% pilocarpine hydrochloride) and to a sympathomimetic agent (0.02% dipivefrine hydrochloride) was examined by assessing changes in pupil diameter. Pupillary supersensitivity to 0.05% pilocarpine was greatest among the PD patients (PD -23.1 +/- 14.4%, MSA -12.4 +/- 11.5%, control -9.5 +/- 8.2%, p < 0.05) but was not correlated with disease duration. Pupillary sensitivity to 0.02% dipivefrine was significantly greater in the PD and MSA patients versus controls (PD 10.5 +/- 12.0%, MSA 11.8 +/- 11.0%, control 3.1 +/- 5.8%, p < 0.05). MSA patients had pupillary sympathetic dysfunction from an early stage, whereas in PD patients it tended to gradually accelerate as the disease advanced. In MSA patients, pupillary sympathetic sensitivity to 0.02% dipivefrine was correlated with the severity of orthostatic hypotension during a head-up tilt test and with the elevation of systolic blood pressure during a noradrenaline infusion test. In PD patients, pupillary sympathetic sensitivity to 0.02% dipivefrine was correlated with a reduction of the heart-to-mediastinum (H/M) ratio using delayed-phase iodine-123 meta-iodobenzylguanidine ((123)I-MIBG) myocardial scintigraphy. These data indicate that eye-drop tests can reveal differences in the progression of pupillary autonomic dysfunction in patients with MSA and PD.

Neurocirculatory Abnormalities in Parkinson Disease With Orthostatic Hypotension

Patients with Parkinson disease often have orthostatic hypotension. Neurocirculatory abnormalities underlying orthostatic hypotension might reflect levodopa treatment. Sixty-six Parkinson disease patients (36 with orthostatic hypotension, 15 off and 21 on levodopa; 30 without orthostatic hypotension) had tests of reflexive cardiovagal gain (decrease in interbeat interval per unit decrease in systolic pressure during the Valsalva maneuver; orthostatic increase in heart rate per unit decrease in pressure); reflexive sympathoneural function (decrease in pressure during the Valsalva maneuver; orthostatic increment in plasma norepinephrine); and cardiac and extracardiac noradrenergic innervation (septal myocardial 6-[18F]fluorodopamine-derived radioactivity; supine plasma norepinephrine). Severity of orthostatic hypotension did not differ between the levodopa-untreated and levodopa-treated groups with Parkinson disease and orthostatic hypotension (-52+/-6 [SEM] versus -49+/-5 mm Hg systolic). The 2 groups had similarly low reflexive cardiovagal gain (0.84+/-0.23 versus 1.33+/-0.35 ms/mm Hg during Valsalva; 0.43+/-0.09 versus 0.27+/-0.06 bpm/mm Hg during orthostasis); and had similarly attenuated reflexive sympathoneural responses (97+/-29 versus 71+/-23 pg/mL during orthostasis; -82+/-10 versus -73+/-8 mm Hg during Valsalva). In patients off levodopa, plasma norepinephrine was lower in those with (193+/-19 pg/mL) than without (348+/-46 pg/mL) orthostatic hypotension. Low values for reflexive cardiovagal gain, sympathoneural responses, and noradrenergic innervation were strongly related to orthostatic hypotension. Parkinson disease with orthostatic hypotension features reflexive cardiovagal and sympathoneural failure and cardiac and partial extracardiac sympathetic denervation, independent of levodopa treatment.

Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group

To evaluate the efficacy of a 10-mg dose of midodrine 3 times per day in improving blood pressure (BP) and ameliorating symptoms of orthostatic hypotension in patients with neurogenic orthostatic hypotension. Midodrine hydrochloride, an alpha-agonist, could improve orthostatic BP by increasing vasomotor and venomotor tone. A total of 171 patients with orthostatic hypotension participated in a multicenter, randomized, placebo-controlled study. They were randomized to a 10-mg dose of midodrine or placebo 3 times per day in a 6-week study, comprising single-blind run-in (at week 1) and washout at weeks 5 and 6, with an intervening double-blind period (weeks 2 to 4). Twenty-five centers, with most patients evaluated in referral centers. The primary end points were improvement in standing systolic BP, symptoms of lightheadedness, and a global symptom relief score (by the investigator and patient separately). Nine patients were not evaluable because of noncompliance or taking concomitant vasoactive medications (3 in the midodrine group, 6 in the placebo group). In the evaluable patients, midodrine resulted in improvements in standing systolic BP at all time points (P<.001 at visits 2, 3, 4, and 5), in reported symptoms by the end of the second week of treatment (P=.001), and in the global symptom relief score rated by both the patient (P=.03) and the investigator (P<.001). There was no effect by center, severity of orthostatic hypotension, use of fludrocortisone or compression garments, or diagnosis. The main adverse effects were those of pilomotor reactions, urinary retention, and supine hypertension. Midodrine is efficacious and safe in the treatment of neurogenic orthostatic hypotension.