-
Clinical and Translational Science May 2024Apomorphine, used to treat OFF episodes in patients with Parkinson's disease (PD), is typically administered via subcutaneous injections. Administration of an oromucosal...
Apomorphine, used to treat OFF episodes in patients with Parkinson's disease (PD), is typically administered via subcutaneous injections. Administration of an oromucosal solution could offer a non-invasive and user-friendly alternative. This two-part clinical study evaluated the safety, tolerability, pharmacokinetics (PK), and dose proportionality of a novel apomorphine hydrochloride oromucosal solution, as well as its relative bioavailability to subcutaneous apomorphine injection and apomorphine sublingual film. In part A of the study, 12 patients with PD received 2 mg oromucosal apomorphine (4% weight/volume) and 2 mg subcutaneous apomorphine in a randomized order, followed by 4 and 8 mg oromucosal apomorphine. In part B of the study, 13 patients with PD received 7 mg oromucosal apomorphine (7% weight/volume) and 30 mg sublingual apomorphine in a randomized order, followed by 14 mg oromucosal apomorphine. Washout between dose administrations in both study parts was at least 2 days. Safety, tolerability, and PK were assessed pre- and post-dose. Both study parts showed that oromucosal apomorphine was generally well-tolerated. Observed side effects were typical for apomorphine administration and included asymptomatic orthostatic hypotension, yawning, fatigue, and somnolence. Oromucosal apomorphine exposure increased with dose, although less than dose proportional. The mean (SD) maximum exposure reached with 14 mg oromucosal apomorphine was 753.0 (298.6) ng*min/mL (area under the plasma concentration-time curve from zero to infinity) and 8.0 (3.3) ng/mL (maximum plasma concentration). This was comparable to exposure reached after 2 mg subcutaneous apomorphine and approximately half of the exposure observed with 30 mg sublingual apomorphine. In summary, clinically relevant plasma concentrations could be reached in PD patients without tolerability issues.
Topics: Aged; Female; Humans; Male; Middle Aged; Administration, Oral; Administration, Sublingual; Antiparkinson Agents; Apomorphine; Biological Availability; Cross-Over Studies; Dose-Response Relationship, Drug; Injections, Subcutaneous; Parkinson Disease; Adult; Aged, 80 and over
PubMed: 38712716
DOI: 10.1111/cts.13796 -
American Journal of Hypertension May 2024To compare pharmacological treatment of hypotension and orthostatic hypotension (OH) initiated based upon a blood pressure (BP) threshold, regardless of symptoms (TXT),...
BACKGROUND
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).
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
PubMed: 38712567
DOI: 10.1093/ajh/hpae057 -
European Heart Journal Open May 2024The pathophysiology of orthostatic hypotension (OH), a common clinical condition, associated with adverse outcomes, is incompletely understood. We examined the...
AIMS
The pathophysiology of orthostatic hypotension (OH), a common clinical condition, associated with adverse outcomes, is incompletely understood. We examined the relationship between OH and circulating endostatin, an endogenous angiogenesis inhibitor with antitumour effects proposed to be involved in blood pressure (BP) regulation.
METHODS AND RESULTS
We compared endostatin levels in 146 patients with OH and 150 controls. A commercial chemiluminescence sandwich immunoassay was used to measure circulating levels of endostatin. Linear and multivariate logistic regressions were conducted to test the association between endostatin and OH. Endostatin levels were significantly higher in OH patients (59 024 ± 2513 pg/mL) vs. controls (44 090 ± 1978pg/mL, < 0.001). A positive linear correlation existed between endostatin and the magnitude of systolic BP decline upon standing ( < 0.001). Using multivariate analysis, endostatin was associated with OH (adjusted odds ratio per 10% increase of endostatin in the whole study population = 1.264, 95% confidence interval 1.141-1.402), regardless of age, sex, prevalent cancer, and cardiovascular disease, as well as traditional cardiovascular risk factors.
CONCLUSION
Circulating endostatin is elevated in patients with OH and may serve as a potential clinical marker of increased cardiovascular risk in patients with OH. Our findings call for external validation. Further research is warranted to clarify the underlying pathophysiological mechanisms.
PubMed: 38708290
DOI: 10.1093/ehjopen/oeae030 -
Parkinsonism & Related Disorders Apr 2024Anti-immunoglobulin-like cell adhesion molecule 5 (IgLON5) disease is a rare autoimmune encephalitis that can mimic progressive supranuclear palsy or corticobasal...
INTRODUCTION
Anti-immunoglobulin-like cell adhesion molecule 5 (IgLON5) disease is a rare autoimmune encephalitis that can mimic progressive supranuclear palsy or corticobasal syndrome. Moreover, anti-IgLON5 disease can present with symptoms characteristic of multiple system atrophy (MSA), such as cerebellar ataxia and autonomic dysfunction. However, the clinical features of anti-IgLON5 disease resembling MSA have not been well established.
METHODS
We enrolled 35 patients with suspected MSA for whom anti-IgLON5 antibody tests were requested. We evaluated immunoglobulin G (IgG) against IgLON5 using cell-based assays. We also summarized the clinical characteristics of patients who were positive for anti-IgLON5 antibodies.
RESULTS
We identified serum and cerebrospinal fluid anti-IgLON5 antibodies in three patients. These patients had many clinical features characteristic of MSA, including parkinsonism, cerebellar ataxia, severe orthostatic hypotension, acute respiratory failure, sleep parasomnia, vocal cord paralysis, and pyramidal tract signs. Clinical features atypical for MSA were myorhythmia, horizontal eye movement restriction, fasciculations, and painful muscle cramps.
CONCLUSION
Anti-IgLON5 disease may be an important differential diagnosis of MSA. A comprehensive physical examination, including assessments of eye movement, lower motor neuron signs, and atypical involuntary movements, is important to avoid misdiagnosis.
PubMed: 38701719
DOI: 10.1016/j.parkreldis.2024.106992 -
Journal of Parkinson's Disease 2024Autonomic dysfunction precedes endothelial dysfunction in Parkinson's disease (PD) and causes blood pressure and circulation abnormalities that are highly disruptive to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Autonomic dysfunction precedes endothelial dysfunction in Parkinson's disease (PD) and causes blood pressure and circulation abnormalities that are highly disruptive to one's quality of life. While exercise interventions have proven helpful for motor symptoms of PD, improving associated non-motor symptoms is limited. Low-intensity resistance training with blood flow restriction (LIRT-BFR) improves autonomic dysfunction in non-PD patients and high-intensity resistance training (HIRT) is recommended for motor symptom improvements for people with PD (PwPD).
OBJECTIVE
To determine the effects of LIRT-BFR and HIRT on homocysteine and autonomic and endothelial function in PwPD and to determine the hemodynamic loads during LIRT-BFR and HIRT in PwPD using a novel exercise protocol.
METHODS
Thirty-eight PwPD were assigned LIRT-BFR, HIRT or to a control (CNTRL) group. The LIRT-BFR and HIRT groups exercised three days per week for four weeks. The LIRT-BFR protocol used 60% limb occlusion pressure (LOP) and performed three sets of 20 repetitions at 20% of the one-repetition maximum (1RM). The HIRT group performed three sets of eight repetitions at 80% 1RM. The CNTRL group was asked to continue their normal daily routines.
RESULTS
LIRT-BFR significantly improved orthostatic hypotension (p = 0.026), homocysteine levels (p < 0.001), peripheral circulation (p = 0.003), supine blood pressure (p = 0.028) and heart rate variability (p = 0.041); LIRT-BFR improved homocysteine levels (p < 0.018), peripheral circulation (p = 0.005), supine blood pressure (p = 0.007) and heart rate variability (p = 0.047) more than HIRT; and hemodynamic loads for LIRT-BFR and HIRT were similar.
CONCLUSIONS
LIRT-BFR may be more effective than HIRT for autonomic and endothelial function improvements in PwPD and hemodynamic loads may be lessened in LIRT-BFR protocols using single-joint exercises with intermittent blood flow restriction. Further research is needed to determine if non-motor symptoms improve over time and if results are sustainable.
Topics: Humans; Resistance Training; Parkinson Disease; Male; Female; Aged; Middle Aged; Endothelium, Vascular; Autonomic Nervous System; Blood Flow Restriction Therapy; Homocysteine; Heart Rate; Blood Pressure
PubMed: 38701159
DOI: 10.3233/JPD-230259 -
Movement Disorders Clinical Practice Jun 2024Blood pressure control in Parkinson's disease (PD) under subthalamic deep brain stimulation (STN-DBS) is influenced by several intertwined aspects, including autonomic...
BACKGROUND
Blood pressure control in Parkinson's disease (PD) under subthalamic deep brain stimulation (STN-DBS) is influenced by several intertwined aspects, including autonomic failure and levodopa treatment.
OBJECTIVE
To evaluate the effect of chronic STN-DBS, levodopa, and their combination on cardiovascular autonomic functions in PD.
METHODS
We performed cardiovascular reflex tests (CRTs) before and 6-months after STN-DBS surgery in 20 PD patients (pre-DBS vs. post-DBS). CRTs were executed without and with medication (med-OFF vs. med-ON).
RESULTS
CRT results and occurrence of neurogenic orthostatic hypotension (OH) did not differ between pre- and post-DBS studies in med-OFF condition. After levodopa intake, the BP decrease during HUTT was significantly greater compared to med-OFF, both at pre-DBS and post-DBS evaluation. Levodopa-induced OH was documented in 25% and 5% of patients in pre-DBS/med-ON and post-DBS/med-ON study.
CONCLUSION
Chronic stimulation did not influence cardiovascular responses, while levodopa exerts a relevant hypotensive effect. The proportion of patients presenting levodopa-induced OH decreases after STN-DBS surgery.
Topics: Humans; Parkinson Disease; Deep Brain Stimulation; Male; Female; Middle Aged; Aged; Levodopa; Autonomic Nervous System; Antiparkinson Agents; Blood Pressure; Subthalamic Nucleus; Hypotension, Orthostatic
PubMed: 38698586
DOI: 10.1002/mdc3.14060 -
Physiology & Behavior Jul 2024Postural change from supine or sitting to standing up leads to displacement of 300 to 1000 mL of blood from the central parts of the body to the lower limb, which causes... (Review)
Review
Postural change from supine or sitting to standing up leads to displacement of 300 to 1000 mL of blood from the central parts of the body to the lower limb, which causes a decrease in venous return to the heart, hence decrease in cardiac output, causing a drop in blood pressure. This may lead to falling down, syncope, and in general reducing the quality of daily activities, especially in the elderly and anyone suffering from nervous system disorders such as Parkinson's or orthostatic hypotension (OH). Among different modalities to study brain function, functional near-infrared spectroscopy (fNIRS) is a neuroimaging method that optically measures the hemodynamic response in brain tissue. Concentration changes in oxygenated hemoglobin (HbO2) and deoxygenated hemoglobin (HHb) are associated with brain neural activity. fNIRS is significantly more tolerant to motion artifacts compared to fMRI, PET, and EEG. At the same time, it is portable, has a simple structure and usage, is safer, and much more economical. In this article, we systematically reviewed the literature to examine the history of using fNIRS in monitoring brain oxygenation changes caused by sudden changes in body position and its relationship with the blood pressure changes. First, the theory behind brain hemodynamics monitoring using fNIRS and its advantages and disadvantages are presented. Then, a study of blood pressure variations as a result of postural changes using fNIRS is described. It is observed that only 58 % of the references concluded a positive correlation between brain oxygenation changes and blood pressure changes. At the same time, 3 % showed a negative correlation, and 39 % did not show any correlation between them.
Topics: Humans; Spectroscopy, Near-Infrared; Brain; Blood Pressure; Posture; Hemodynamics
PubMed: 38697274
DOI: 10.1016/j.physbeh.2024.114574 -
The Journal of Spinal Cord Medicine May 2024Reduced ocular perfusion pressure (OPP) from hypotension and consistent OPP variability due to blood pressure (BP) fluctuations are predisposing factors for glaucoma....
BACKGROUND
Reduced ocular perfusion pressure (OPP) from hypotension and consistent OPP variability due to blood pressure (BP) fluctuations are predisposing factors for glaucoma. Low resting BP and orthostatic hypotension (OH) in spinal cord injury (SCI) patients may increase the risk of glaucoma post-injury. This study investigated BP, intraocular pressure (IOP), and OPP changes between supine and sitting positions in SCI and normal individuals.
METHODS
Twenty SCI cases (high paraplegia, T1-T6 = 6; low paraplegia, T7-L3 = 14) and matched controls (1:1) were included. Systolic and diastolic BP (SBP and DBP) were measured digitally, and IOP with rebound tonometry. Measurements were taken one minute apart in both positions. Mean arterial pressure (MAP) was calculated, and OPP was determined using position-specific formulas.
RESULTS
No SCI subjects exhibited OH. Both groups experienced significant BP increment ( < 0.05) from supine to sitting. SBP increased by 4.4 ± 8.4 mmHg (SCI) and 3.6 ± 6.2 mmHg (normal), while DBP increased by 4.2 ± 5.1 mmHg (SCI) and 6.7 ± 5.5 mmHg (normal). IOP and OPP decreased significantly ( < 0.05) after postural change in both groups, yet differences between them were not significant. Analysis by injury level revealed lower parameter values in high paraplegia than in low paraplegia, with the latter group showing a more significant reduction in OPP after postural change.
CONCLUSION
Postural changes differently affect BP, IOP, and OPP in SCI compared to normal individuals, with variations based on the level of SCI. While not directly assessing glaucoma, the study offers insights into ocular hemodynamics in SCI compared to normals.
PubMed: 38695735
DOI: 10.1080/10790268.2024.2345446 -
Kardiochirurgia I Torakochirurgia... Mar 2024Although primary spontaneous pneumothorax is a common disease in young adults, each thoracic surgery department performs different procedures for its management.
INTRODUCTION
Although primary spontaneous pneumothorax is a common disease in young adults, each thoracic surgery department performs different procedures for its management.
AIM
The optimal time of postoperative mobilization is not yet standardized in lung surgery.
MATERIAL AND METHODS
This study included male patients with a primary spontaneous pneumothorax who underwent wedge resection of the upper lobe of the lungs via uniportal video-assisted thoracoscopic surgery. Patients were encouraged to stand up within the first postoperative hour. Mobilization was defined as standing and walking at least 100 m from the bed. If orthostatic hypotension occurred, mobilization was postponed for 30 min. Immediately after surgery, intravenous fluids were discontinued, and patients were instructed to drink water. The analgesic treatment needs, length of hospitalization, drainage, and discharge times were recorded.
RESULTS
A total of 43 patients were operated on by the same surgeon. All operations were ended with uniportal video-assisted thoracoscopic surgery. Wedge resection is most commonly indicated for recurrent ipsilateral pneumothorax. Patients walked 345 (range: 150-510) m on the department corridor following bed rest. Paracetamol (2 g) and dexketoprofen (100 mg) were intravenously administered as postoperative analgesia to 76.7% of patients. Narcotic drugs were not needed.
CONCLUSIONS
Mobilization was recommended in the first hour following uniportal video-assisted thoracoscopic surgery for primary spontaneous pneumothorax.
PubMed: 38693989
DOI: 10.5114/kitp.2024.138497 -
Primary Care Jun 2024Autonomic disorders can present with hypotension, gastrointestinal, genitourinary symptoms, and heat intolerance. Diabetes is the most common causes of autonomic...
Autonomic disorders can present with hypotension, gastrointestinal, genitourinary symptoms, and heat intolerance. Diabetes is the most common causes of autonomic failure, and management should focus on glucose control to prevent developing autonomic symptoms. The most prevalent cause of dysautonomia, or autonomic dysfunction, is Postural Orthostatic Tachycardia Syndrome (POTS). Autonomic testing characterizes causes for nonspecific symptoms but is not necessary in patients with classic presentations. Treatment for autonomic dysfunction and failure focus on discontinuing offending medications, behavioral modification, and pharmacologic therapy to decrease symptom severity. Autonomic failure has no cure; therefore, the focus remains on improving quality of life.
Topics: Humans; Autonomic Nervous System Diseases; Postural Orthostatic Tachycardia Syndrome; Primary Health Care; Quality of Life
PubMed: 38692780
DOI: 10.1016/j.pop.2024.02.006