Symptomatic Orthostatic Hypotension Research Articles

Norepinephrine Reuptake Inhibition, an Emergent Treatment for Neurogenic Orthostatic Hypotension.

The NET (norepinephrine transporter) is situated in the prejunctional plasma membrane of noradrenergic neurons. It is responsible for >90% of the norepinephrine uptake that is released in the autonomic neuroeffector junction. Inhibitors of this cell membrane transporter, known as norepinephrine reuptake inhibitors (NRIs), are commercially available for the treatment of depression and attention deficit hyperactivity disorder. These agents increase norepinephrine levels, potentiating its action in preganglionic and postganglionic adrenergic neurons, the latter through activation of α-1 adrenoreceptors. Previous studies found that patients with neurogenic orthostatic hypotension can improve standing blood pressure and reduce symptoms of neurogenic orthostatic hypotension after a single administration of the selective NRI atomoxetine. This effect was primarily observed in patients with impaired central autonomic pathways with otherwise normal postganglionic sympathetic fibers, known as multiple system atrophy. Likewise, patients with normal or high norepinephrine levels may benefit from NRIs. The long-term efficacy of NRIs for the treatment of neurogenic orthostatic hypotension-related symptoms is currently under investigation. In summary, an in-depth understanding of the pathophysiology of neurogenic orthostatic hypotension resulted in the discovery of a new therapeutic pathway targeted by NRI.

Treatment of orthostatic hypotension during acute inpatient rehabilitation after spinal cord injury: usual care versus anti-hypotensive therapy.

To compare pharmacological treatment of hypotension and orthostatic hypotension (OH) initiated based upon a blood pressure (BP) threshold, regardless of symptoms (TXT), to usual care pharmacological treatment of symptomatic hypotension (UC), during acute inpatient rehabilitation (AIR) following spinal cord injury (SCI). Block randomization, based on the neurological level of injury as: cervical lesions (C1-C8); high thoracic lesions (T1-T5) and low thoracic lesions (T6-T12), was used to determine responses to the primary question "was the therapy session affected by low BP or concern for low BP development?". Study participants and therapists were unaware of group assignment. A total of 66 participants enrolled; 25 (38%) in the TXT group, 29 (44%) in the UC group, and 12 (18%) withdrew. Responses to the primary question were recorded for 32 participants, 15 in the TXT and 17 in the UC group. There was an average of 81±51 therapy sessions/participant in the TXT and 60±27 sessions/participant in the UC group. Of those therapy sessions, low BP or concerns for low BP affected an average of 9±8 sessions/participant in the TXT group and 10±12 sessions/participant in the UC group. Neither the total number of therapy sessions (p=0.16) nor group assignment (p=0.83) significantly predicted the number of sessions affected by low BP. These data are not conclusive but indicate that the treatment of asymptomatic hypotension and OH does not increase time spent in therapy compared to usual care treatment of symptomatic hypotension and OH in newly injured patients with SCI.

Orthostatic hypotension in Parkinson's disease: Sit-to-stand vs. supine-to-stand protocol and clinical correlates

BackgroundScreening for orthostatic hypotension (OH) is integral in Parkinson's disease (PD) management, yet evidence-based guidelines on best practice methods for diagnosing OH in PD are lacking. MethodsWe investigated the frequency and correlates of OH, symptomatic OH, and neurogenic OH, in a large consecutively recruited PD cohort (n = 318), and compared the diagnostic performance of the sit-to-stand vs. the supine-to-stand blood pressure (BP) test. We evaluated the utility of continuous BP monitoring and tilt table testing in patients with postural symptoms or falls who were undetected to have OH with clinic-based BP measurements. Disease severity, fluid intake, orthostatic and overactive bladder symptoms, falls, comorbidities and medication history were evaluated. ResultsPatients’ mean age was 66.1 ± 9.5years, with mean disease duration 7.8 ± 5.5years. OH frequency was 35.8 % based on the supine-to-stand test. OH in PD was significantly associated with older age, lower body mass index, longer disease duration, worse motor, cognitive and overactive bladder symptoms and functional disabilities, falls, and lower fluid intake. A similar profile was seen with asymptomatic OH. Three quarters of OH were neurogenic, with the majority also having supine hypertension. The sit-to-stand test had a sensitivity of only 0.39. One quarter of patients were additionally diagnosed with OH during continuous BP monitoring. ConclusionsThe sit-to-stand test substantially underdiagnoses OH in PD, with the important practice implication that supine-to-stand measurements may be preferred. Screening for OH is warranted even in asymptomatic patients. Adequate fluid intake, treatment of urinary dysfunction and falls prevention are important strategies in managing PD patients with OH.

Heart rate variability and its association with symptoms of orthostatic hypotension in spinal cord injury

Context/objective To assess differences in autonomic function using heart rate variability (HRV) parameters between people with and without orthostatic hypotension (OH), and to determine symptoms of OH in people with spinal cord injury (SCI). Methods R-R interval and blood pressure (BP) data were recorded using Finometer PRO® in both the supine position and at a 60-degree tilt using a tilt table, each lasting for 6 minutes. R-R interval data were processed using the Kubios HRV analysis software to convert R-R interval into time and frequency domains for further analysis. Results Compared to the non-OH group, the SCI group with OH exhibited lower values for root mean square of the successive differences (RMSSD) and standard deviation of normal-to-normal interval (SDNN), along with an elevated heart rate during tilt-up. Participants with OH symptoms had a lower average heart rate in the supine and 60-degree positions compared to asymptomatic participants. Logistic regression analysis indicated that SDNN in the supine position correlated with the presence of OH, and that the mean heart rate in the 60-degree position was related to the presence of symptoms. Conclusions Differences in HRV parameters were observed in people with SCI and OH, suggesting a reduced parasympathetic activity in the supine position, likely as a response to maintain homeostasis in BP regulation. Despite the presence or absence of OH symptoms, there was no difference in HRV parameters. This finding suggests that autonomic function may not be the primary determinant of these symptoms, with other factors likely being more influential.

Synchronous Bilateral Brachial Blood Pressure Measurements Increased Orthostatic Hypotension Detection in the Elderly.

Orthostatic hypotension (OH) is a common clinical sign, but its detection rate is low, and it is difficult to repeat because there is no standardized screening method available. This study aimed to establish a method for detecting blood pressure and assess whether it could increase the OH detection rate in the elderly. From May to October, 2022, 178 patients with symptomatic OH and 286 subjects with asymptomatic OH were selected. BP from the bilateral brachial artery was measured using two electronic sphygmomanometers on both arms at the same time, in the order of supine, sitting, and standing at 0-3 min. OH should meet 20/10 mmHg, standing BP minus sitting BP. The OH detection rates were calculated and compared. The symptomatic OH group was more often older, slimmer, had lower ADL scores, and contained fewer smokers (all P< 0.05). The detection rate of the symptomatic OH group using the modified method was 59.55%, which was higher than that of the routine method (34.83% vs. 59.55%, P<0.05). The detection rate using the modified method in the OH group with asymptomatic OH was 20.63%, which was higher than that of the routine method (20.63% vs. 5.59%, P< 0.01). Synchronous measurement of bilateral brachial artery BP in supine, sitting, and standing positions increased the detection rate of OH in the elderly.

Study protocol for the Heads-Up trial: a phase II randomized controlled trial investigating head-up tilt sleeping to alleviate orthostatic intolerance in Parkinson’s Disease and parkinsonism

BackgroundIn persons with Parkinson’s Disease (PD) or certain forms of atypical parkinsonism, orthostatic hypotension is common and disabling, yet often underrecognized and undertreated. About half of affected individuals also exhibit supine hypertension. This common co-occurrence of both orthostatic hypotension and supine hypertension complicates pharmacological treatments as the treatment of the one can aggravate the other. Whole-body head-up tilt sleeping (HUTS) is the only known intervention that may improve both. Evidence on its effectiveness and tolerability is, however, lacking, and little is known about the implementability.MethodsIn this double-blind multicenter randomized controlled trial (phase II) we will test the efficacy and tolerability of HUTS at different angles in 50 people with PD or parkinsonism who have both symptomatic orthostatic hypotension and supine hypertension. All participants start with one week of horizontal sleeping and subsequently sleep at three different angles, each maintained for two weeks. The exact intervention will vary between the randomly allocated groups. Specifically, the intervention group will consecutively sleep at 6°, 12° and 18°, while the delayed treatment group starts with a placebo angle (1°), followed by 6° and 12°. We will evaluate tolerability using questionnaires and compliance to the study protocol. The primary endpoint is the change in average overnight blood pressure measured by a 24-hour ambulatory blood pressure recording. Secondary outcomes include orthostatic blood pressure, orthostatic tolerance, supine blood pressure, nocturia and various other motor and non-motor tests and questionnaires.DiscussionWe hypothesize that HUTS can simultaneously alleviate orthostatic hypotension and supine hypertension, and that higher angles of HUTS are more effective but less tolerable. The Heads-Up trial will help to clarify the effectiveness, tolerability, and feasibility of this intervention at home and can guide at-home implementation.Trial registrationClinicalTrials.gov NCT05551377; Date of registration: September 22, 2022.

FRI218 Von Hippel-Lindau With Pheochromocytoma And Severe Orthostatic Hypotension

Abstract Disclosure: N. Ebrahimi: None. C.G. Rivas Pajuelo: None. R. Habibi: None. S. Tariq: None. S.A. Penquite: None. Introduction: Von Hippel-Lindau (VHL) syndrome clinically manifests with benign and malignant tumors across multiple organ systems including the cerebellum, retina, kidney, and adrenal glands. Pheochromocytoma occurs in 25-30% of patients with VHL. Up to 50% of patients with pheochromocytoma present with hypertension or paroxysmal hypertension, although patients can be normotensive on presentation. Patients with pheochromocytoma are often severely volume depleted due to chronic vasoconstriction. Here we present a case of VHL with pheochromocytoma complicated by profound orthostatic hypotension after initiation of alpha-blockade. Case Presentation: A 32-year-old man presented for evaluation of progressive headache and diplopia. Patient was normotensive on initial presentation with BP 129/80mmHg. Brain MRI with contrast subsequently revealed a posterior fossa cystic mass with an avidly enhancing central nodule concerning for hemangioblastoma. Given these findings, a CT chest/abdomen/pelvis was obtained, which demonstrated a 4.6 x 5.0 cm right adrenal mass, several enhancing renal lesions, and multiple cystic lesions throughout the pancreas. This constellation of radiological findings was clinically concerning for VHL. Further endocrinologic work-up revealed plasma metanephrines 663 pg/mL (insert reference range here), plasma catecholamines 770 pg/mL (insert reference range here), which confirmed the diagnosis of pheochromocytoma. Alpha blockade was initiated with doxazosin 4 mg BID, and a high sodium diet (insert g/day). Shortly after initiation of doxazosin, patient developed severe orthostatic hypotension despite salt loading and volume resuscitation. Ultimately doxazosin was discontinued, and surgery was postponed due to severe symptomatic orthostatic hypotension limiting patient’s ability to get out of bed. High sodium diet was continued on hospital discharge and alpha-adrenergic blockade was later re-initiated which patient is tolerating well. Patient is pending adrenalectomy in the coming weeks. Discussion: Orthostatic hypotension in pheochromocytoma is expected due to volume depletion from chronic vasoconstriction. Alpha adrenergic blockade is required to alleviate hypertension, allow for adequate volume expansion, and to prevent a hypertensive crisis intraoperatively. Clinicians should be aware of the commercially available alpha-adrenergic antagonists and when they should be temporarily discontinued. There is no preferred alpha-adrenergic antagonist agent, however doxazosin has shown to cause less orthostatic hypotension and does not have such an antihypertensive effect as of Phenoxybenzamine. Presentation: Friday, June 16, 2023

163 Examining the appropriateness of tilt-testing within a community integrated care hub for older persons services

Abstract Background Tilt-testing has been widely used in acute hospitals for more than 20 years in Ireland. Its use in community settings has been promoted in recent years with the development of the National Integrated Care Programme for Older Persons (NICPOP). In our integrated care hub our focus lies in the assessment of falls and frailty. We propose to examine if the current rational for performing tilt-testing has showed a diagnostic yield. Methods We retrospectively reviewed all tilt reports in the ambulatory care hub from November 2021 to May 2023. We examined the rationale for ordering the test, the number of patients who received a diagnosis of Orthostatic Hypotension (OH) and treatment that was commenced. Results 59 tilt reports were examined between the 18 month period. The average age of the patients were 83 (range 68–93). The male to female ratio was 1:1.3. All patients had an indicator for testing. The 5 indicators that emerged were falls, syncope, orthostatic intolerance, lying and standing blood pressure drop and dizziness. 11/59 (19%) patients had one indicator, 18/59 (31%) patients had two indicators, 15/59 (25%) patients had three indicators and 15/59 (25%) patients had four indicators for performing a tilt. OH was diagnosed in 36/59 (61%) patients of whom 9/36 (25%) had symptomatic OH during both HUT and AS, 8/36 (22%) had symptoms during HUT alone, 6/36 (17%) had symptoms during AS and 9/36 (25%) were asymptomatic throughout testing. 4/36 (11%) had no documentation regarding their symptoms during tilting. De-prescribing was performed in 16/36 (44%) patients and Midodrine was commenced in 18/36 (50%) patients with fludrocortisone being started on 2/36 (6%) patients. Conclusion We demonstrated a high yield from the tilt-test investigations and in combination with Ambulatory BP monitoring had a significant number of medications de-prescribed. The greater preponderance of more than one indicator for tilt-testing was greater than what we perceived.

A Case Report of Dizziness with Postural Hypotension Improved by Korean Medicine Treatment

Background: Postural hypotension refers to a drop in systolic blood pressure of 20 mmHg or diastolic blood pressure of 10 mmHg or more within three minutes after standing up from lying down. Symptoms of postural hypotension not only include dizziness and blurred vision but also fatigue, cognitive decline, leg weakness, headache, and, in severe cases, fainting. Postural hypotension is a phenomenon that occurs in about 6% of the total population, and in Korea, the number of patients with postural hypotension is continuously increasing. Both pharmacological and non-drug therapies, which are treatment methods for this disease, do not show a satisfactory symptom improvement effect.Case summary: A 65-year-old male patient who visited the hospital complaining of dizziness and paresthesia due to postural hypotension was treated with acupuncture, moxibustion, and herbal medicine. For symptom evaluation, the numeric rating scale (NRS) of each symptom was used, and blood pressure change according to posture was measured. After treatment, the NRSs of dizziness and dysesthesia were decreased, and blood pressure changes according to posture was improved.Conclusion: This case report suggests that Korean medicine treatment, including acupuncture, electro-acupuncture, moxibustion, and herbal medicine, can be an effective treatment for dizziness with postural hypotension.

Pacemaker Implants and Their Influence on the Daily Life of Patients with Dementia with Lewy Bodies: A Qualitative Case Study.

Dementia with Lewy bodies (DLB) is an incurable form of dementia associated with detriments to the daily life of patients and carers from their family. Symptoms of orthostatic hypotension, syncope, and falls are supportive of DLB diagnosis. These symptoms may also be present among people with sick sinus syndrome (SSS), and subsequent pacemaker treatment to manage bradyarrhythmia is associated with improved cognitive function. The prevalence of SSS seems to be higher among people with underlying Lewy body pathology compared to the general age-matched population (5.2% vs. 0.17%). To our knowledge, how people with DLB and their family carers may experience pacemaker treatment to manage bradyarrhythmia has not been previously reported. Therefore, the aim of this study was to explore how people with DLB experience daily life following a pacemaker implant to manage associated symptoms of bradyarrhythmia. A qualitative case study design was used. Two men with DLB and their spouse carers were repeatedly interviewed as a dyad within 1year following implant of a dual-chamber rate-adaptive (DDD-CLS) pacemaker to manage SSS in the men. Content analysis was used to assess the qualitative interview data collected. Three categories emerged: (1) gaining control, (2) maintaining a social life, and (3) being influenced by concurrent diseases. Less syncope/falls and remote pacemaker monitoring increased a sense of control in everyday life, while perceived physical and/or cognitive improvements influenced social participation. The men were still affected by concurrent diseases, which continuously influenced each couple's daily life. Identifying and managing concurrent bradyarrhythmia through a pacemaker implant could improve well-being for people with DLB.

Enrolling patients in Cardiac Amyloid Reaching for Extended Survival (CARES) trials: Two placebo-controlled, double-blind, randomized, international phase 3 trials assessing CAEL-101 in patients with Mayo stage IIIa or stage IIIb AL amyloidosis.

TPS8071 Background: Light-chain (AL) amyloidosis is a rare, progressive, systemic disorder caused by plasma cell dyscrasia (PCD). Amyloid fibrils deposit in organs leading to progressive organ damage and death. Prognosis is poor for patients with cardiac involvement. Median survival is 24 and 4 months for patients in Mayo Stages IIIa and IIIb (based on the 2013 European Modification of the Mayo 2004 staging criteria), respectively. The standard of care (SoC) is anti-PCD therapy to suppress amyloid fibril generation. As yet, there are no therapies that remove deposited fibrils. CAEL-101 is a monoclonal antibody that binds to amyloid fibrils and may facilitate their systemic removal, improve organ function, and patient survival. These ongoing trials will evaluate the efficacy and safety of CAEL-101 as first-in-class treatment to reduce amyloid burden in patients with cardiac AL amyloidosis. Notably, 301 (Mayo Stage IIIb) is the first randomized, placebo-controlled efficacy clinical trial to formally assess the effects of a pharmacological in this severely ill population. Because the median expected survival for Mayo Stage IIIb patients is far shorter than for Mayo Stage IIIa patients, the resulting sample size required for the Mayo Stage IIIb study is less than for the Mayo Stage IIIa study. The objective of these trials is to evaluate the efficacy and safety of CAEL-101 when administered concurrently with SoC anti-PCD therapy in treatment-naïve patients with cardiac AL amyloidosis in Mayo Stages IIIb (NCT04504825; 301) or IIIa (NCT04512235; 302). Methods: These international, multicenter, double-blind, randomized, phase 3 trials, initiated in 2020, are enrolling patients at &gt; 100 sites in &gt; 20 countries. Newly diagnosed adults with AL amyloidosis stage IIIb or IIIa measurable hematologic disease, and histopathological diagnosis of amyloidosis with cardiac involvement are eligible. Patients with other forms of amyloidosis, symptomatic orthostatic hypotension, or supine systolic blood pressure &lt; 90 mm Hg are ineligible. Patients in Mayo Stages IIIb (N = 124) and IIIa (N = 267) are being randomized 2:1 to receive once-weekly IV infusions of CAEL-101 (1000 mg/m2) or placebo for 4 weeks, followed by maintenance dosing every 2 weeks. In these event-driven studies, treatment will continue to a minimum of 101 and 79 events for 301 and 302, respectively. Patients will receive concurrent institutional SoC anti-PCD therapy at the discretion of the investigator. Overall survival (primary endpoint) will be analyzed via time-to-event log-rank statistics. Secondary endpoints include functional outcomes, quality of life, and echocardiography. Clinical trial information: NCT04504825 , NCT04512235 .

Ampreloxetine Versus Droxidopa in Neurogenic Orthostatic Hypotension: A Comparative Review.

Neurogenic orthostatic hypotension (nOH) is a disabling problem of autonomic dysfunction in patients with Parkinson's disease, which is associated with poor quality of life and higher mortality rates. The purpose of this literature review was to explore and compare the efficacy and safety of droxidopa (an existing treatment) and ampreloxetine (a newer medication) in the treatment of nOH. We used a mixed-method literature review that addresses the epidemiology, pathophysiology, and pharmacological and non-pharmacological management of nOHin Parkinson's disease in a general way, with a more exploratory approach to droxidopa- and ampreloxetine-controlled trial studies. We included a total of 10 studies of randomized controlled trials with eight studies focused on droxidopaand two studies focused on ampreloxetine. These two drugs were analyzed and compared based on the collected individual study results. Treatment of nOH inParkinson's disease patients with droxidopa or ampreloxetine showed clinically meaningful and statistically significant improvements relative to placebo on the components of the OHSA (Orthostatic Hypotension Symptom Assessment) composite score and OHDAS (Orthostatic Hypotension Daily Activity Scale composite scores) composite score. Droxidopa had an improved effect on daily activities, with an associated increase in standing systolic blood pressure (BP), but the long-term efficacy of droxidopa has not been documented. Standing systolic BP was maintained by ampreloxetine and worsened after the withdrawal phase. This highlights the importance of conducting further researchwhich will help us to improve the therapeutic approach for patients with nOH and Parkinson's disease.

Gadolinium enhancement in cervical dorsal roots in a patient with acute autonomic and sensory neuropathy: a case report

BackgroundWe report an enhancement of the dorsal roots on gadolinium-enhanced cervical magnetic resonance imaging (MRI) in a patient with acute autonomic and sensory neuropathy (AASN).Case presentationA 38-year-old woman visited our university hospital for dizziness and fainting while rising from sitting or lying down and a tingling sensation in the whole body, including her limbs, torso, and abdomen, which was sustained for 15 days. The patient had hyperalgesia in nearly her entire body and slight motor weakness in her bilateral upper and lower limbs. Autonomic dysfunction was confirmed using autonomic testing. Furthermore, the nerve conduction study showed an absence of sensory nerve action potentials in all evaluated peripheral nerves. Cervical MRI was performed 18 days after dysautonomia onset. In the axial T1-gadolinum-enhanced MRIs, enhancement in cervical ventral and dorsal nerve roots and the posterior column of the spinal cord were observed, and the axial T2-weighted MRI showed high signal intensity in the posterior column of the cervical spinal cord. Considering the clinical, electrophysiological and imaging findings, the patient was diagnosed with AASN. A total dose of 90 g (2 g/kg) of intravenous immunoglobulin was administered over 5 days. At the follow-up at 4 years after AASN symptom onset, the hyperalgesia and orthostatic hypotension symptoms improved. However, her systolic blood pressure intermittently decreased to < 80 mmHg.ConclusionGadolinium-enhanced MRI may facilitate the accurate and prompt diagnosis of AASN.

Randomised controlled trials of antihypertensive therapy: does exclusion of orthostatic hypotension alter treatment effect? A systematic review and meta-analysis.

Management of antihypertensive therapy is challenging in patients with symptomatic orthostatic hypotension, a population often excluded from randomised controlled trials of antihypertensive therapy. In this systematic review and meta-analysis, we sought to determine whether the association of antihypertensive therapy and adverse events (e.g. falls, syncope), differed among trials that included or excluded patients with orthostatic hypotension. We performed a systematic review and meta-analysis of randomised controlled trials comparing blood pressure lowering medications to placebo, or different blood pressure targets on falls or syncope outcomes and cardiovascular events. A random-effects meta-analysis was used to estimate a pooled treatment-effect overall in subgroups of trials that excluded patients with orthostatic hypotension and trials that did not exclude patients with orthostatic hypotension, and tested P for interaction. The primary outcome was fall events. 46 trials were included, of which 18 trials excluded orthostatic hypotension and 28 trials did not. The incidence of hypotension was significantly lower in trials that excluded participants with orthostatic hypotension (1.3% versus 6.2%, P < 0.001) but not incidences of falls (4.8% versus 8.8%; P = 0.40) or syncope (1.5% versus 1.8%; P = 0.67). Antihypertensive therapy was not associated with an increased risk of falls in trials that excluded (OR 1.00, 95% CI; 0.89-1.13) or included (OR 1.02, 95% CI; 0.88-1.18) participants with orthostatic hypotension (P for interaction = 0.90). The exclusion of patients with orthostatic hypotension does not appear to affect the relative risk estimates for falls and syncope in antihypertensive trials.

Dynamic Alterations in Cerebral Hemodynamics Measured by Portable Near-Infrared Spectroscopy in Orthostatic Hypotension and Intolerance.

We aimed to evaluate dynamic alterations in cerebral total hemoglobin concentration (HbT) in individuals with orthostatic hypotension (OH) and orthostatic intolerance (OI) symptoms using a portable near-infrared spectroscopy (NIRS) system. Participants comprised 238 individuals (mean age, 47.9 years) without a history of cardiovascular, neurodegenerative, or cerebrovascular diseases, including those with unexplained OI symptoms and healthy volunteers. Participants were categorized by the presence of OH based on the supine-to-stand blood pressure (BP) drop and OI symptoms using on OH questionnaires: classic OH (OH-BP), OH symptoms alone (OH-Sx), and control groups. Random case-control matching sets were constructed, resulting in 16 OH-BP and 69 OH-Sx-control sets. The time-derivative of HbT change in the prefrontal cortex during the squat-to-stand maneuver was measured using a portable NIRS system. There were no differences in demographics, baseline BP, and heart rate among matched sets. The peak time of maximum slope variation in HbT change, indicating the recovery rate and speed of cerebral blood volume (CBV) change, was significantly longer in OH-Sx and OH-BP groups than in the control group under transition to a standing position after squatting. In the OH-BP subgrouping, the peak time of maximum slope variation in HbT change was significantly longer only in OH-BP with OI symptoms, but did not differ between OH-BP without OI symptoms and controls. Our results suggest that OH and OI symptoms are associated with dynamic alterations in cerebral HbT. Regardless of the severity of the postural BP drop, OI symptoms are associated with prolonged CBV recovery.

GUIDED BREATHING EXERCISE MODULATES BLOOD PRESSURE FOR PEOPLE WITH SPINAL CORD INJURY

BACKGROUND People with Spinal Cord Injury (SCI) often suffer from autonomic dysfunction, including orthostatic intolerance. These effects can be similar to those that astronauts experience while exposed to microgravity. To improve post-flight orthostatic intolerance, and other symptoms of autonomic dysfunction, scientists at NASA designed a biofeedback protocol, Autogenic Feedback Training Exercise (AFTE). AFTE combines specific autogenic exercises (e.g., self-suggestion of warmth in the hands) with biofeedback of multiple physiological responses (i.e., blood pressure [BP], heart rate, body temperature, breathing rate). We modified this protocol by adding guided breathing exercises and immersive virtual reality (VR) and tested it among people with and without SCI. The study aims to determine if AFTE is viable for improving autonomic dysfunction in individuals with SCI. We hypothesize that participants with SCI will improve symptoms of orthostatic hypotension and be able to modulate BP toward normotensive values after eight sessions of AFTE. METHODS/DESIGN A convenience sample of five (n=5) participants with chronic cervical SCI: two women (body weight 90+/−13Kg, height 164+/−2Cm, age 48+/−18), three men (body weight 96+/−37, height 180+/−5Kg, age 40+/−28) and four (n=4) participants without SCI: two women (body weight 57+/−9 Kg, height 164+/ 9 Cm, age 22+/−1) and two men (body weight 78 Kg +/−18, height 182 cm +/−5, age 27+/−2) participated in the study. Training consisted of eight 3-minute cycles of alternating relaxing then stimulating breathing, interoception (i.e., noticing inner body sensation), and VR. The relaxing breathing to lower BP consisted of making the “mmm” sound with three long nasal exhales to lower blood pressure. The stimulating breathing to raise BP consisted of three series of ten quick nasal exhales. After each of the eight cycles, participants were given feedback on whether they met their goal of increasing of decreasing MAP 5 mmHg during stimulation or relaxation cycles respectively. Training was performed twice a week for five weeks. RESULTS Participants successfully modulated their BP during the breathing exercise portion of the training. Participants reported they were able to use the technique at home after training was completed. CONCLUSIONS Guided breathing exercises could provide a readily available method of BP modification without side effects, potentially enabling more exercise compliance for people with SCI.

Effect of Lower Limb vs. Abdominal Compression on Mobility in Orthostatic Hypotension: A Single-Blinded, Randomized, Controlled, Cross-Over Pilot Study in Parkinson's Disease.

Orthostatic hypotension (OH) in Parkinson's disease (PD) is frequent and associated with impairments in quality of life and reduced activities of daily living. Abdominal binders (AB) and compression stockings (CS) have been shown to be effective non-pharmacological treatment options. Here, we investigate the effect of AB versus CS on physical activity using a digital mobility outcome (sit to stand [STS] frequency) collected in the usual environment as a primary endpoint. We enrolled 16 PD patients with at least moderate symptomatic OH. In a randomized, single-blinded, controlled, crossover design, participants were assessed without OH treatment over 1 week (baseline), then were given AB or CS for 1 week and subsequently switched to the other treatment arm. The primary outcome was the number of real-life STS movements per hour as assessed with a lower back sensor. Secondary outcomes included real-life STS duration, mean/systolic/diastolic blood pressure drop (BPD), orthostatic hypotension questionnaire (OHQ), PD quality of life (PDQ-39), autonomic symptoms (SCOPA-AUT), non-motor symptoms (NMSS), MDS-UPDRS, and activities of daily living (ADL/iADL). Real-life STS frequency on CS was 4.4±4.1 per hour compared with 3.6±2.2 on AB and 3.6±1.8 without treatment (p = 1.0). Concerning the secondary outcomes, NMSS showed significant improvement with CS and AB. OHQ and SCOPA-AUT improved significantly with AB but not CS, and mean BPD drop worsened with CS but not AB. Mean STS duration, PDQ-39, MDS-UPDRS, ADL, and iADL did not significantly change. Both AB and CS therapies do not lead to a significant change of physical activity in PD patients with at least moderate symptomatic OH. Secondary results speak for an effect of both therapies concerning non-motor symptoms, with superiority of AB therapy over CS therapy.

Hypotensive unawareness in Parkinson's disease-related autonomic dysfunction.

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.

Dual-phase 18 F-FP-CIT positron emission tomography and cardiac 123 I-MIBG scintigraphy of Parkinson's disease patients with GBA mutations: evidence of the body-first type?

Parkinson's disease (PD) with glucocerebrosidase (GBA) gene mutation (GBA-PD) is known to show more rapid clinical progression than sporadic PD without GBA mutation (sPD). This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter uptake and cardiac meta-iodobenzylguanidine (MIBG) uptake of GBA-PD in comparison to sPD. Through next-generation sequencing analysis targeting 41 genes, a total of 16 GBA-PD and 24 sPD patients (sex, age matched) were enrolled in the study, and the clinical, dual-phase [18 F]-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (1 8 F-FP-CIT) positron emission tomography (PET)and cardiac 123 I-MIBG scintigraphy results were compared between the two groups. The GBA-PD group had higher rates of rapid eye movement sleep behavior disorder, orthostatic hypotension and neuropsychiatric symptoms than the sPD group. Early-phase 18 F-FP-CIT PETshowed significantly lower standard uptake value ratio on bilateral posterior parietal cortex (0.94 ± 0.05 vs. 1.02 ± 0.04, p=0.011) and part of the occipital cortex (p < 0.05) in the GBA-PD group than the sPD group. In striatal dopamine transporter uptake, the regional standard uptake value ratio, asymmetry index and caudate-to-putamen ratio were similar between the two groups. The GBA-PD group had a lower heart-to-mediastinum uptake ratio in 123 I-MIBG scintigraphy than the sPD group. The GBA-PD patients showed decreased regional perfusion in the bilateral posterior parietal and occipital cortex. Cardiac sympathetic denervation and non-motor symptoms (orthostatic hypotension, rapid eye movement sleep behavior disorder) were more common in GBA-PD than sPD. These findings suggest that GBA-PD patients have more widespread peripheral (extranigral) α-synuclein accumulation, representing a body-first PD subtype.

ODP016 A case of adrenal incidentaloma in a patient with latent tuberculosis

Abstract An adrenal incidentaloma can be either a nonfunctioning adrenocortical adenoma or may cause disease, such as adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastasis. However, less commonly, it can be a manifestation of infection such as tuberculosis. The case is a 40-year-old male who emigrated from China two years ago, referred to the endocrine clinic after he was found to have a 3 cm right adrenal macroadenoma on MRCP after hospitalization for acute cholecystitis. The patient was also found to have positive Quantiferon, but CXR was clear. He was started on isoniazid therapy for latent tuberculosis and was later switched to rifampin postoperatively. One month after hospital discharge, he was evaluated by Endocrinology. Vital signs, including BP were normal with no symptoms of dizziness or orthostatic hypotension. He had no symptoms of adrenal insufficiency or excess. Electrolytes, renal, liver function tests, and CBC were within normal. Albumin was 4.3g/dL(RR 3.4-5). Fasting 8 AM labs: ACTH 9 pg/mL (RR 0-47), cortisol 10.10 ug/dL (RR 5.3-22.5), DHEA S 130 mcg/dL (RR 80-560), plasma metanephrines and normetanephrines and midnight salivary cortisol were normal, aldosterone 10 ng/dL, renin 1.49 ng/mL/h with ARR of 6.7. Adrenal CT w/wo contrast showed right adrenal mass with absolute washout 78% and relative washout 53% consistent with adenoma, as well as bilateral subcentimeter lipid rich adenomas and marked mesenteric lymphadenopathy. Mycobacterium tuberculosis complex spreads to the adrenal glands hematogenously. Clinical manifestations of adrenal insufficiency in tuberculosis may take years to take effect, after 90% of gland destruction occurs. The majority of patients with active or recently acquired disease (&amp;lt;2 years) have bilateral adrenal enlargement, while calcification and atrophy is found with remote infection or inactive disease. The adrenals can be enlarged in patients with pulmonary tuberculosis even without active involvement of the glands solely due to stress and inflammation. The hypothalamic-pituitary-adrenal (HPA) axis can be activated or even under-activated in active pulmonary tuberculosis. Cortisol levels return to baseline after anti-tuberculous treatment. Rarely tuberculosis can cause adrenal incidentaloma. Adrenal biopsy is not necessary for primary adrenal insufficiency with bilateral adrenal enlargement in a patient with proven extra-adrenal tuberculosis. However, about 12% of patients with adrenal tuberculosis have no evidence of active extra-adrenal tuberculosis. Adrenal biopsy was refused but is generally necessary in these patients to prove adrenal involvement by tuberculosis. Our case highlights the fact that tuberculosis should be considered in the differential of adrenal masses. Reference: Fassnacht M, Arlt W, Bancos I, et al. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2016 Aug;175(2): G1-G34. doi: 10.1530/EJE-16-0467. PMID: 27390021. Presentation: No date and time listed