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Wu Y, Feng W, Chen Q, He M, Bai H, Peng R, Liang B, Ma M, Tuo N, Zheng L. Impact of scheduled water intake on mild cognitive impairment in patients with orthostatic hypotension. Sci Rep 2025; 15:10269. [PMID: 40133603 PMCID: PMC11937325 DOI: 10.1038/s41598-025-94818-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Accepted: 03/17/2025] [Indexed: 03/27/2025] Open
Abstract
Orthostatic blood pressure (BP) dysregulation can impair cerebral blood perfusion and cognition. Water intake prevents syncope caused by orthostatic hypotension (OHypo) and improves orthostatic tolerance. However, research on scheduled water intake's effect on the association between OHypo and cognition is limited. This study aimed to investigate the impact of scheduled water intake on orthostatic BP dysregulation and mild cognitive impairment (MCI). This cross-sectional study was conducted in rural Fuxin, Liaoning Province, China, using cohort data. Water intake patterns were self-reported, and orthostatic BP was measured. MCI was assessed with the Chinese version of the Montreal Cognitive Assessment-Basic (MoCA-BC).Latent class mixed models were applied to identify systolic BP trajectory patterns. Logistic regression was used to examine the association between orthostatic BP abnormality and MCI, adjusting for potential confounders and including an interaction term for orthostatic BP abnormality and water intake regularity. Linear regression was used to analyze the relationship between orthostatic BP abnormality and total MoCA-BC score. Subgroup analyses were conducted based on age and water intake regularity. The study included 1576 participants: 1236 (78.4%) had normal recovery, 234 (14.8%) had delayed recovery, 36 (2.3%) had OHypo, and 70 (4.5%) had orthostatic hypertension. The average age was 63.2 ± 7.7 years, with a daily water intake of 1612.5 ± 978.8 ml; 1055 (66.9%) were female. Unscheduled water intake significantly interacted with OHypo on MCI (OR 5.82; 95% CI 1.17-35.34; P = 0.039). After adjusting for confounders, scheduled water intake was associated with a lower OR of MCI in those with OHypo (OR 0.11; 95% CI 0.02-0.44; P = 0.003), while unscheduled water intake showed no significant association (OR 0.99; 95% CI 0.41-2.57; P = 0.985). Scheduled water intake is linked to a lower risk of MCI in individuals with OHypo, suggesting a protective role. Promoting scheduled water intake might be inversely associated with MCI in OHypo patients. Further longitudinal studies are needed to confirm these findings and understand the mechanisms involved.
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Affiliation(s)
- Yani Wu
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wenjing Feng
- Hainan Provincial Center for Disease Control and Prevention (Hainan Academy of Preventive Medicine), Haikou, China
| | - Qian Chen
- Department of Electroencephalography, Shengjing Hospital of China Medical University, Shenyang, China
| | - Mengyao He
- Department of Biostatistics and Epidemiology, School of Public Health, China Medical University, Shenyang, China
| | - He Bai
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ruiheng Peng
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bin Liang
- Department of Cardiovascular Medicine, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Mingfeng Ma
- Department of Cardiovascular Medicine, Fenyang Hospital Affiliated With Shanxi Medical University, Fenyang, Shanxi, China.
| | - Nan Tuo
- Clinical Research Centre, The International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Liqiang Zheng
- Hainan Branch, Shanghai Children's Medical Center, School of Medicine,Shanghai Jiao Tong University, Sanya, China.
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Khalil I, Sayad R, Kedwany AM, Sayed HH, Caprara ALF, Rissardo JP. Cardiovascular dysautonomia and cognitive impairment in Parkinson's disease (Review). MEDICINE INTERNATIONAL 2024; 4:70. [PMID: 39355336 PMCID: PMC11443310 DOI: 10.3892/mi.2024.194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 09/03/2024] [Indexed: 10/03/2024]
Abstract
Cognitive impairment is a prevalent non-motor symptom of Parkinson's disease (PD), which can result in significant disability and distress for patients and caregivers. There is a marked variation in the timing, characteristics and rate at which cognitive decline occurs in patients with PD. This decline can vary from normal cognition to mild cognitive impairment and dementia. Cognitive impairment is associated with several pathophysiological mechanisms, including the accumulation of β-amyloid and tau in the brain, oxidative stress and neuroinflammation. Cardiovascular autonomic dysfunctions are commonly observed in patients with PD. These dysfunctions play a role in the progression of cognitive impairment, the incidents of falls and even in mortality. The majority of symptoms of dysautonomia arise from changes in the peripheral autonomic nervous system, including both the sympathetic and parasympathetic nervous systems. Cardiovascular changes, including orthostatic hypotension, supine hypertension and abnormal nocturnal blood pressure (BP), can occur in both the early and advanced stages of PD. These changes tend to increase as the disease advances. The present review aimed to describe the cognitive changes in the setting of cardiovascular dysautonomia and to discuss strategies through which these changes can be modified and managed. It is a multifactorial process usually involving decreased blood flow to the brain, resulting in the development of cerebral ischemic lesions, an increased presence of abnormal white matter signals in the brain, and a potential influence on the process of neurodegeneration in PD. Another possible explanation is this association being independent observations of PD progression. Patients with clinical symptoms of dysautonomia should undergo 24-h ambulatory BP monitoring, as they are frequently subtle and underdiagnosed.
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Affiliation(s)
- Ibrahim Khalil
- Faculty of Medicine, Alexandria University, Alexandria 5372066, Egypt
| | - Reem Sayad
- Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | | | - Hager Hamdy Sayed
- Department of Nuclear Medicine, Assuit University, Assuit 71515, Egypt
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Kim KT, Lee JH, Hong JP, Park JW, Lee SU, Park E, Kim BJ, Kim JS. Blood Pressure Variability and Ocular Vestibular-Evoked Myogenic Potentials Are Independently Associated With Orthostatic Hypotension. J Clin Neurol 2024; 20:571-579. [PMID: 39505309 PMCID: PMC11543387 DOI: 10.3988/jcn.2024.0092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Revised: 06/03/2024] [Accepted: 07/19/2024] [Indexed: 11/08/2024] Open
Abstract
BACKGROUND AND PURPOSE We delineated the association between otolithic dysfunction and blood pressure (BP) variability. METHODS We prospectively recruited 145 consecutive patients (age=71 [59-79] years, median [interquartile range]; 76 females) with orthostatic intolerance between December 2021 and December 2023 at a tertiary hospital in South Korea. Each patient underwent evaluations of cervical and ocular vestibular-evoked myogenic potentials (oVEMPs), 24-h noninvasive ambulatory BP monitoring (ABPM), and a head-up tilt-table test using the Finometer device. As measures of BP variability, the standard deviations (SDs) of the systolic BP (SBPSD) and the diastolic BP were calculated based on serial ABPM recordings. Patients were divided into those with orthostatic hypotension (OH, n=68) and those with a normal head-up tilt-table test despite orthostatic intolerance (NOI, n=77) groups. RESULTS A multivariable logistic regression analysis showed that OH was associated with bilateral oVEMP abnormalities (p=0.021), SBPSD (p=0.012), and female sex (p=0.004). SBPSD was higher in patients with OH than in those with NOI (p<0.001), and was not correlated with n1-p1 amplitude (p=0.491) or normalized p13-n23 amplitude (p=0.193) in patients with OH. The sensitivity and specificity for differentiating OH from NOI were 72.1% and 67.5%, respectively, at a cutoff value of 12.7 mm Hg for SBPSD, with an area under the receiver operating characteristic curve of 0.73. CONCLUSIONS Bilaterally deficient oVEMP responses may be associated with OH regardless of 24-h BP variability, reflecting the integrity of the otolith-autonomic reflex during orthostasis. Alternatively, 24-h BP variability is predominantly regulated by the baroreflex, which also participates in securing orthostatic tolerance complementary to the vestibulo-autonomic reflex.
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Affiliation(s)
- Keun-Tae Kim
- Department of Neurology, Korea University Medical Center, Seoul, Korea
| | - Jeong-Heon Lee
- Department of Neurology, Korea University Medical Center, Seoul, Korea
| | - Jun-Pyo Hong
- Department of Neurology, Korea University Medical Center, Seoul, Korea
| | - Jin-Woo Park
- Department of Neurology, Korea University Medical Center, Seoul, Korea
| | - Sun-Uk Lee
- Department of Neurology, Korea University Medical Center, Seoul, Korea
- Neurotology and Neuro-ophthalmology Laboratory, Korea University Medical Center, Seoul, Korea.
| | - Euyhyun Park
- Neurotology and Neuro-ophthalmology Laboratory, Korea University Medical Center, Seoul, Korea
- Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Korea
| | - Byung-Jo Kim
- Department of Neurology, Korea University Medical Center, Seoul, Korea
- BK21 FOUR Program in Learning Health Systems, Korea University, Seoul, Korea
| | - Ji-Soo Kim
- Dizziness Center, Clinical Neuroscience Center, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Neurology, Seoul National University College of Medicine, Seoul, Korea
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Kominami K, Akino M, Kanai M. Efficacy of Neuro-muscular Electrical Stimulation for Orthostatic Hypotension Associated with Long-term Disuse and Diabetic Autonomic Neuropathy: A Case Report. Phys Ther Res 2024; 27:180-185. [PMID: 39866392 PMCID: PMC11756561 DOI: 10.1298/ptr.e10298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 07/16/2024] [Indexed: 01/28/2025]
Abstract
Patient Background: A 75-year-old man had difficulty moving around at home because of loss of appetite and neglect of medication for several days. He was brought to the emergency room and admitted on the same day with a diagnosis of dehydration and diabetic ketoacidosis. He started physical therapy (PT), had frequent fainting and presyncope due to hypotension, and had difficulty leaving bed. The patient was transferred to our hospital to continue PT. Test results on admission were as follows: short physical performance battery (SPPB) [points], 1/12 points; chair stand 5 times (CS5) [sec], not possible; functional independent measure (FIM) [points], 66/126; standing test: blood pressure (BP) [mmHg], 130/60/HR [beats per minute], 76 in supine, 90/56/79 in sitting, 70/-/79 in standing. PROCESS After transfer, BP continued to fall markedly and he frequently fainted and required assistance with nearly all activities of daily living (ADL). Neuromuscular electrical stimulation (NMES) of the thigh and lower leg was performed five times a week for 30 min. After approximately 3 days of NMES, BP decreased slowly, presyncopic symptoms disappeared, and he could leave bed more frequently and for longer periods. The patient became independent in ADL and was discharged on Day 142. Results at discharge were as follows: SPPB, 11/12; CS5, 13.5; FIM, 114/126. DISCUSSION Although NMES is not effective for orthostatic hypotension (OH) associated with diabetic autonomic neuropathy (DAN), stabilization of BP early after the introduction of NMES may have been due to its peripheral sympathetic nerve-stimulating effect. CONCLUSION The combination of exercise therapy and NMES for OH caused by DAN can alleviate hypotension.
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Affiliation(s)
| | - Masatoshi Akino
- Department of Internal Medicine, Sapporo Kiyota Hospital, Japan
| | - Motoshi Kanai
- Department of Internal Medicine, Sanseikai Kitano Hospital, Japan
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Fedorowski A, Fanciulli A, Raj SR, Sheldon R, Shibao CA, Sutton R. Cardiovascular autonomic dysfunction in post-COVID-19 syndrome: a major health-care burden. Nat Rev Cardiol 2024; 21:379-395. [PMID: 38163814 DOI: 10.1038/s41569-023-00962-3] [Citation(s) in RCA: 43] [Impact Index Per Article: 43.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/13/2023] [Indexed: 01/03/2024]
Abstract
Cardiovascular autonomic dysfunction (CVAD) is a malfunction of the cardiovascular system caused by deranged autonomic control of circulatory homeostasis. CVAD is an important component of post-COVID-19 syndrome, also termed long COVID, and might affect one-third of highly symptomatic patients with COVID-19. The effects of CVAD can be seen at both the whole-body level, with impairment of heart rate and blood pressure control, and in specific body regions, typically manifesting as microvascular dysfunction. Many severely affected patients with long COVID meet the diagnostic criteria for two common presentations of CVAD: postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. CVAD can also manifest as disorders associated with hypotension, such as orthostatic or postprandial hypotension, and recurrent reflex syncope. Advances in research, accelerated by the COVID-19 pandemic, have identified new potential pathophysiological mechanisms, diagnostic methods and therapeutic targets in CVAD. For clinicians who daily see patients with CVAD, knowledge of its symptomatology, detection and appropriate management is more important than ever. In this Review, we define CVAD and its major forms that are encountered in post-COVID-19 syndrome, describe possible CVAD aetiologies, and discuss how CVAD, as a component of post-COVID-19 syndrome, can be diagnosed and managed. Moreover, we outline directions for future research to discover more efficient ways to cope with this prevalent and long-lasting condition.
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Affiliation(s)
- Artur Fedorowski
- Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
- Department of Medicine, Karolinska Institute, Stockholm, Sweden.
- Department of Clinical Sciences, Lund University, Malmö, Sweden.
| | | | - Satish R Raj
- Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Robert Sheldon
- Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Cyndya A Shibao
- Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Richard Sutton
- Department of Clinical Sciences, Lund University, Malmö, Sweden
- Department of Cardiology, Hammersmith Hospital, National Heart & Lung Institute, Imperial College, London, UK
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Yang M, Peng R, Wang Z, Li M, Song Y, Niu J, Ji Y. Epidemiology and Risk Factors for Orthostatic Hypotension and Its Severity in Residents Aged > 60 years: A Cross-Sectional Study. Int J Hypertens 2024; 2024:9945051. [PMID: 38445022 PMCID: PMC10914424 DOI: 10.1155/2024/9945051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 02/06/2024] [Accepted: 02/10/2024] [Indexed: 03/07/2024] Open
Abstract
This cross-sectional study investigated the epidemiology and risk factors associated with orthostatic hypotension (OH) and its severity in older adults residing in the Jizhou community of Tianjin and the Jimei community of Xiamen. The study, conducted from March to September 2019, involved adults aged over 60. A comprehensive questionnaire survey was administered, resulting in the enrolment of 4383 older adults. The overall prevalence of OH was found to be 11.7% (516 out of 4383). Notably, a significant gender difference was observed, with a prevalence of 10% among males (194 out of 1926) and 13.1% among females (322 out of 2457) (P=0.002). Among individuals with OH, 332 exhibited mild symptoms, 64 had moderate OH, 58 had severe OH cases, and 50 have very severe OH. Multivariable logistic regression analysis revealed that being female, widowed, engaging in general social activities, and a history of hypertension, migraines, heart disease, cerebrovascular disease, and mental health conditions (anxiety and depression) were independently associated with OH. Ordinal logistic regression analysis further confirmed that hypertension, migraine, and a history of general anesthesia surgery were independently associated with the severity of OH. This study highlights a relatively high prevalence of OH among older adults in the Jizhou community of Tianjin and the Jimei community of Xiamen, China. The identified risk factors, particularly social activities, and hypertension, significantly influence the severity of OH. Further examination is required to corroborate these findings and investigate potential interventions.
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Affiliation(s)
- Mingni Yang
- Department of Neurology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, China
| | - Ruiqiang Peng
- Department of Neurology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, China
| | - Zetuo Wang
- Department of Neurology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, China
| | - Miaoduan Li
- Department of Neurology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, China
| | - Yehua Song
- Department of Neurology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, China
| | - Jianping Niu
- Department of Neurology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, China
| | - Yong Ji
- Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Department of Neurology, Tianjin Dementia Institute, Tianjin Huanhu Hospital, Tianjin, China
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Ye Y, Murdock DJ, Chen C, Liedtke W, Knox CA. Epidemiology of myasthenia gravis in the United States. Front Neurol 2024; 15:1339167. [PMID: 38434198 PMCID: PMC10907989 DOI: 10.3389/fneur.2024.1339167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 02/01/2024] [Indexed: 03/05/2024] Open
Abstract
Introduction Global studies of epidemiology of myasthenia gravis (MG) have pointed to increasing prevalence of this rare autoimmune disorder affecting the neuromuscular synapse; however, no new data for the USA were available for decades. We aimed to estimate the incidence rate and prevalence of MG in a large-scale insured US population. Methods We conducted a population-based retrospective cohort study to estimate the annual incidence and prevalence of MG cases in the USA during 2017. Using a previously validated algorithm, we identified cases of MG in two Truven Health MarketScan databases, which during 2017 included a sample of approximately 20 million commercially insured and Medicare recipients, plus 10 million Medicaid recipients. We report crude incidence and prevalence and calculated age-and sex-standardized estimates for the USA based on the 2017 American Community Survey. We estimated the number of adult cases during 2021 by extrapolating from the stratified estimates to the population size from the 2021 American Community Survey. Results From the US commercially/Medicare-insured cohort, we calculated an age-and sex-standardized incidence of 68.5 new cases per million person-years with an adjusted prevalence of 316.4 per million. Within the Medicaid-insured population, similar yet slightly lower numbers emerged: the adjusted incidence was 49.7 new cases per million person-years, and the adjusted prevalence rate was 203.7 cases per million. Given our results, we were able to estimate that there were approximately 82,715 US adults living with MG in 2021 (or an estimated 320.2 cases per million adults in the USA). We observed a strong effect of age and sex when stratifying the identified incidence rate and prevalence, with a pattern of female preponderance among the younger age brackets, a male preponderance for older cases in the commercially/Medicare-insured cohort, and the disease incidence and prevalence steadily increasing with age. Discussion Our updated US population-based estimates of MG epidemiology demonstrate an increase in the previously reported incidence and prevalence from over 20 years ago, in keeping with developments in westernized, industrialized countries. Notable findings of steadily increasing prevalence with age, driven by robust increases in elderly males, prompts questions for basic-translational research, therapeutics, and public health.
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Affiliation(s)
- Yun Ye
- The Division of Epidemiology, The Ohio State University, Columbus, OH, United States
| | | | - Chao Chen
- Regeneron Pharmaceuticals, Inc., Tarrytown, NY, United States
| | | | - Caitlin A. Knox
- Regeneron Pharmaceuticals, Inc., Tarrytown, NY, United States
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Chen B, Yang W, Luo Y, Tan EK, Wang Q. Non-pharmacological and drug treatment of autonomic dysfunction in multiple system atrophy: current status and future directions. J Neurol 2023; 270:5251-5273. [PMID: 37477834 DOI: 10.1007/s00415-023-11876-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 07/11/2023] [Accepted: 07/11/2023] [Indexed: 07/22/2023]
Abstract
Multiple system atrophy (MSA) is a sporadic, fatal, and rapidly progressive neurodegenerative disease of unknown etiology that is clinically characterized by autonomic failure, parkinsonism, cerebellar ataxia, and pyramidal signs in any combination. Early onset and extensive autonomic dysfunction, including cardiovascular dysfunction characterized by orthostatic hypotension (OH) and supine hypertension, urinary dysfunction characterized by overactive bladder and incomplete bladder emptying, sexual dysfunction characterized by sexual desire deficiency and erectile dysfunction, and gastrointestinal dysfunction characterized by delayed gastric emptying and constipation, are the main features of MSA. Autonomic dysfunction greatly reduces quality of life and increases mortality. Therefore, early diagnosis and intervention are urgently needed to benefit MSA patients. In this review, we aim to discuss the systematic treatment of autonomic dysfunction in MSA, and focus on the current methods, starting from non-pharmacological methods, such as patient education, psychotherapy, diet change, surgery, and neuromodulation, to various drug treatments targeting autonomic nerve and its projection fibers. In addition, we also draw attention to the interactions among various treatments, and introduce novel methods proposed in recent years, such as gene therapy, stem cell therapy, and neural prosthesis implantation. Furthermore, we elaborate on the specific targets and mechanisms of action of various drugs. We would like to call for large-scale research to determine the efficacy of these methods in the future. Finally, we point out that studies on the pathogenesis of MSA and pathophysiological mechanisms of various autonomic dysfunction would also contribute to the development of new promising treatments and concepts.
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Affiliation(s)
- BaoLing Chen
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Gongye Road 253, Guangzhou, 510282, Guangdong, People's Republic of China
| | - Wanlin Yang
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Gongye Road 253, Guangzhou, 510282, Guangdong, People's Republic of China
| | - Yuqi Luo
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Gongye Road 253, Guangzhou, 510282, Guangdong, People's Republic of China
| | - Eng-King Tan
- Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore, Singapore.
- Duke-NUS Medical School, Singapore, Singapore.
| | - Qing Wang
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Gongye Road 253, Guangzhou, 510282, Guangdong, People's Republic of China.
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Kim D, Kim N, Lee Y, Kim S, Kwon J. Sound stimulation using the individual's heart rate to improve the stability and homeostasis of the autonomic nervous system. Physiol Rep 2023; 11:e15816. [PMID: 37726255 PMCID: PMC10509153 DOI: 10.14814/phy2.15816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 08/23/2023] [Accepted: 08/24/2023] [Indexed: 09/21/2023] Open
Abstract
OBJECTIVES In this study, we explain the role of enhancing the stability and homeostasis of the autonomic nervous system (ANS) by proposing the average heart rate sound resonance (aHRSR), a sound stimulation to prevent imbalance of ANS due to dynamic movement. The effect of aHRSR on ANS was analyzed through the time and frequency domain of heart rate variability (HRV) using the photoplethysmogram data (PPG) of 22 participants (DUIRB-202109-12). METHOD When the subjects performed dynamic movements that could cause changes in the ANS, HRV indicators using PPG data for 5 min before and after the movements were analyzed according to the presence or absence of aHRSR. The standard deviation of the NN intervals (SDNN), the square root of the mean squared differences of the NN intervals (RMSSD), low-frequency band (LF), and high-frequency band (HF), which represent sympathetic and parasympathetic nerve activity, were used as indicators, where SNDD and LF represent total ANS and sympathetic activity, while RMSSD and HF represent parasympathetic activity. RESULTS As the effects of aHRSR on dynamic movement, the recovery time of RR interval was advanced by about 15 s, SDNN increased from ([44.16 ± 13.11] to [47.85 ± 15.16]) ms, and RMSSD increased from ([23.73 ± 9.95] to [31.89 ± 12.48]) ms (p < 0.05), increasing the stability of the ANS and reducing instability. The effect of homeostasis of the ANS according to aHRSR is also shown in reducing the change rate of LF from (-13.83 to -8.83) %, and the rate of change of HF from (10.59 to 3.27) %. CONCLUSIONS These results suggest that aHRSR can affect the cardiovascular system by assisting physiological movements that occur during dynamic movement.
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Affiliation(s)
- Daechang Kim
- Department of Medical BiotechnologyDongguk UniversityGyeonggi‐doKorea
| | - Nahyeon Kim
- Department of Medical BiotechnologyDongguk UniversityGyeonggi‐doKorea
| | - Younju Lee
- Department of Medical BiotechnologyDongguk UniversityGyeonggi‐doKorea
| | - Sungmin Kim
- Department of Medical BiotechnologyDongguk UniversityGyeonggi‐doKorea
| | - Jiyean Kwon
- Department of Medical Device and HealthcareDongguk UniversitySeoulKorea
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Kim KT, Lee SU, Kim JB, Choi JY, Kim BJ, Kim JS. Augmented ocular vestibular-evoked myogenic potentials in postural orthostatic tachycardia syndrome. Clin Auton Res 2023; 33:479-489. [PMID: 37115468 DOI: 10.1007/s10286-023-00943-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 04/08/2023] [Indexed: 04/29/2023]
Abstract
PURPOSE To delineate the association between otolith function and changes in mean orthostatic blood pressure (BP) and heart rate (HR) in patients with postural orthostatic tachycardia syndrome (POTS). METHODS Forty-nine patients with POTS were prospectively recruited. We analyzed the results of ocular vestibular-evoked myogenic potentials (oVEMPs) and cervical vestibular-evoked myogenic potentials (cVEMPs), as well as head-up tilt table tests using a Finometer. The oVEMP and cVEMP responses were obtained using tapping stimuli and 110 dB tone-burst sounds, respectively. We measured maximal changes in 5-s averaged systolic BP (SBP), diastolic BP (DBP), and heart rate (HR) within 15 s and during 10 min after tilting. We compared the results with those of 20 age- and sex-matched healthy participants. RESULTS The n1-p1 amplitude of oVEMPs was larger in patients with POTS than in healthy participants (p = 0.001), whereas the n1 latency (p = 0.280) and interaural difference (p = 0.199) did not differ between the two. The n1-p1 amplitude was a positive predictor for POTS (odds ratio 1.07, 95% confidence interval 1.01-1.13, p = 0.025). Body weight (p = 0.007) and n1-p1 amplitude of oVEMP (p = 0.019) were positive predictors for ΔSBP15s in POTS, whereas aging was a negative predictor (p = 0.005). These findings were not observed in healthy participants. CONCLUSIONS Augmented utricular inputs may be associated with a relative predominance of sympathetic over vagal control of BP and HR, especially for an early response during orthostasis in patients with POTS. Overt sympathoexcitation due to exaggerated utricular input and lack of readaptation may be associated with the pathomechanism of POTS.
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Affiliation(s)
- Keun-Tae Kim
- Department of Neurology, Korea University Medical Center, 73 Goryeodae-ro, Seongbuk-gu, Seoul, 02841, South Korea
| | - Sun-Uk Lee
- Department of Neurology, Korea University Medical Center, 73 Goryeodae-ro, Seongbuk-gu, Seoul, 02841, South Korea.
| | - Jung-Bin Kim
- Department of Neurology, Korea University Medical Center, 73 Goryeodae-ro, Seongbuk-gu, Seoul, 02841, South Korea
| | - Jeong-Yoon Choi
- Department of Neurology, Seoul National University College of Medicine, Seoul, South Korea
- Dizziness Center, Clinical Neuroscience Center, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Byung-Jo Kim
- Department of Neurology, Korea University Medical Center, 73 Goryeodae-ro, Seongbuk-gu, Seoul, 02841, South Korea
- BK21 FOUR Program in Learning Health Systems, Korea University, Seoul, South Korea
| | - Ji-Soo Kim
- Department of Neurology, Seoul National University College of Medicine, Seoul, South Korea
- Dizziness Center, Clinical Neuroscience Center, Seoul National University Bundang Hospital, Seongnam, South Korea
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Hoxhaj P, Shah S, Muyolema Arce VE, Khan W, Sadeghzadegan A, Singh S, Collado GF, Goyal A, Khawaja I, Botlaguduru D, Razzaq W, Abdin ZU, Gupta I. Ampreloxetine Versus Droxidopa in Neurogenic Orthostatic Hypotension: A Comparative Review. Cureus 2023; 15:e38907. [PMID: 37303338 PMCID: PMC10257554 DOI: 10.7759/cureus.38907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/11/2023] [Indexed: 06/13/2023] Open
Abstract
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 nOH in 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 droxidopa and two studies focused on ampreloxetine. These two drugs were analyzed and compared based on the collected individual study results. Treatment of nOH in Parkinson'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 research which will help us to improve the therapeutic approach for patients with nOH and Parkinson's disease.
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Affiliation(s)
| | - Shruti Shah
- Internal Medicine, Byramjee Jeejeeboy (BJ) Medical College, Pune, IND
| | | | | | | | - Saumya Singh
- Internal Medicine, Gujarat Medical Education & Research Society (GMERS) Medical College and Hospital, Gujarat, IND
| | - Gaudy F Collado
- Internal Medicine, Fleet Medical Unit, Philippine Fleet, Philippine Navy, Cavite City, PHL
| | - Abhishek Goyal
- Internal Medicine, Kasturba Medical College, Manipal, Manipal, IND
| | - Imran Khawaja
- Internal Medicine, Ayub Medical Institute, Abbottabad, PAK
| | | | - Waleed Razzaq
- Internal Medicine, Services Hospital Lahore, Lahore, PAK
| | - Zain U Abdin
- Medicine, District Head Quarters Hospital, Faisalabad, PAK
| | - Ishita Gupta
- Medicine, Dr. Rajendra Prasad Government Medical College, Tanda, IND
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12
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Utricular dysfunction in patients with orthostatic hypotension. Clin Auton Res 2022; 32:431-444. [PMID: 36074194 DOI: 10.1007/s10286-022-00890-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Accepted: 08/22/2022] [Indexed: 01/31/2023]
Abstract
PURPOSE To delineate the association between otolithic dysfunction and orthostatic hypotension (OH). METHODS We retrospectively reviewed the medical records of 382 patients who presented with orthostatic dizziness at a tertiary dizziness center between July 2017 and December 2021. Patients were included for analyses when they had completed ocular (oVEMP) and/or cervical vestibular-evoked myogenic potentials (cVEMP), and head-up tilt table test with a Finometer (n = 155). We compared the results between the patients with OH (n = 38) and those with NOI (normal head-up tilt table test despite orthostatic intolerance, n = 117). RESULTS Thirty-eight patients with OH were further categorized as either classic (n = 30), delayed (n = 7), or initial (n = 1) types. Multivariable logistic regression showed that OH was associated with high baseline systolic BP (p = 0.046), presence of heart failure (p = 0.016), and unilateral oVEMP abnormalities (p = 0.016). n1 latency of oVEMP were negatively correlated with the maximal changes of systolic blood pressure (BP) in 15 s ([Formula: see text]SBP15s, p = 0.013), 3 min ([Formula: see text]SBP3min, p = 0.005) and 10 min ([Formula: see text]SBP10min, p = 0.002). In contrast, the n1-p1 amplitude was positively correlated with [Formula: see text]SBP15s (p = 0.029). Meanwhile, p13 latency of cVEMP was negatively correlated with [Formula: see text]SBP10min (p = 0.018). CONCLUSIONS Our study provides evidence of utricular dysfunction related to OH.
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13
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Polverino P, Ajčević M, Catalan M, Bertolotti C, Furlanis G, Marsich A, Buoite Stella A, Accardo A, Manganotti P. Comprehensive telemedicine solution for remote monitoring of Parkinson's disease patients with orthostatic hypotension during COVID-19 pandemic. Neurol Sci 2022; 43:3479-3487. [PMID: 35301614 PMCID: PMC8930064 DOI: 10.1007/s10072-022-05972-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 02/21/2022] [Indexed: 12/04/2022]
Abstract
OBJECTIVE Orthostatic hypotension (OH) represents a frequent but under-recognized phenomenon in Parkinson's disease (PD). During COVID-19 pandemic, Information and Communication Technologies (ICT) have become pivotal in the management of chronic diseases like PD, not only to assess motor impairment, but also for vital signs monitoring. This pilot study aimed to propose a real-time remote home-monitoring system and protocol for PD patients with OH. METHODS Vital parameters were acquired by wireless devices and transmitted to an ICT platform, providing data and smart notifications to the healthcare provider through an interactive web portal. Eight patients with idiopathic PD and OH underwent 5-day monitoring. Data about OH episodes, therapeutic interventions, impact on daily activities, and patient satisfaction were collected and analyzed. RESULTS The proposed solution allowed the identification of 65 OH episodes and subsequent medical interventions. Thirty-five episodes were asymptomatic, especially in the postprandial and in the afternoon recordings. Systolic-blood-pressure (SBP) and diastolic-blood-pressure (DBP) were significantly lower in symptomatic episodes, while the pressure drops resulted significantly higher in presence of symptoms. High usability and patient satisfaction scores were observed. CONCLUSION The proposed home-monitoring system and protocol have proved to provide useful information and to allow prompt interventions in the management of PD patients with OH during COVID-19 pandemic.
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Affiliation(s)
- Paola Polverino
- Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Strada di Fiume, 447-34149, Trieste, Italy
| | - Miloš Ajčević
- Department of Engineering and Architecture, University of Trieste, Via A. Valerio, 10-34127, Trieste, Italy
| | - Mauro Catalan
- Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Strada di Fiume, 447-34149, Trieste, Italy
| | - Claudio Bertolotti
- Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Strada di Fiume, 447-34149, Trieste, Italy
| | - Giovanni Furlanis
- Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Strada di Fiume, 447-34149, Trieste, Italy
| | | | - Alex Buoite Stella
- Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Strada di Fiume, 447-34149, Trieste, Italy
| | - Agostino Accardo
- Department of Engineering and Architecture, University of Trieste, Via A. Valerio, 10-34127, Trieste, Italy
| | - Paolo Manganotti
- Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste - ASUGI, University of Trieste, Strada di Fiume, 447-34149, Trieste, Italy.
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14
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Suri JS, Paul S, Maindarkar MA, Puvvula A, Saxena S, Saba L, Turk M, Laird JR, Khanna NN, Viskovic K, Singh IM, Kalra M, Krishnan PR, Johri A, Paraskevas KI. Cardiovascular/Stroke Risk Stratification in Parkinson's Disease Patients Using Atherosclerosis Pathway and Artificial Intelligence Paradigm: A Systematic Review. Metabolites 2022; 12:metabo12040312. [PMID: 35448500 PMCID: PMC9033076 DOI: 10.3390/metabo12040312] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 03/25/2022] [Accepted: 03/29/2022] [Indexed: 12/20/2022] Open
Abstract
Parkinson’s disease (PD) is a severe, incurable, and costly condition leading to heart failure. The link between PD and cardiovascular disease (CVD) is not available, leading to controversies and poor prognosis. Artificial Intelligence (AI) has already shown promise for CVD/stroke risk stratification. However, due to a lack of sample size, comorbidity, insufficient validation, clinical examination, and a lack of big data configuration, there have been no well-explained bias-free AI investigations to establish the CVD/Stroke risk stratification in the PD framework. The study has two objectives: (i) to establish a solid link between PD and CVD/stroke; and (ii) to use the AI paradigm to examine a well-defined CVD/stroke risk stratification in the PD framework. The PRISMA search strategy selected 223 studies for CVD/stroke risk, of which 54 and 44 studies were related to the link between PD-CVD, and PD-stroke, respectively, 59 studies for joint PD-CVD-Stroke framework, and 66 studies were only for the early PD diagnosis without CVD/stroke link. Sequential biological links were used for establishing the hypothesis. For AI design, PD risk factors as covariates along with CVD/stroke as the gold standard were used for predicting the CVD/stroke risk. The most fundamental cause of CVD/stroke damage due to PD is cardiac autonomic dysfunction due to neurodegeneration that leads to heart failure and its edema, and this validated our hypothesis. Finally, we present the novel AI solutions for CVD/stroke risk prediction in the PD framework. The study also recommends strategies for removing the bias in AI for CVD/stroke risk prediction using the PD framework.
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Affiliation(s)
- Jasjit S. Suri
- Stroke Monitoring and Diagnostic Division, AtheroPoint™, Roseville, CA 95661, USA; (A.P.); (I.M.S.)
- Correspondence: ; Tel.: +1-(916)-749-5628
| | - Sudip Paul
- Department of Biomedical Engineering, North Eastern Hill University, Shillong 793022, India; (S.P.); (M.A.M.)
| | - Maheshrao A. Maindarkar
- Department of Biomedical Engineering, North Eastern Hill University, Shillong 793022, India; (S.P.); (M.A.M.)
| | - Anudeep Puvvula
- Stroke Monitoring and Diagnostic Division, AtheroPoint™, Roseville, CA 95661, USA; (A.P.); (I.M.S.)
- Annu’s Hospitals for Skin & Diabetes, Gudur 524101, India
| | - Sanjay Saxena
- Department of CSE, International Institute of Information Technology, Bhuneshwar 751003, India;
| | - Luca Saba
- Department of Radiology, University of Cagliari, 09121 Cagliari, Italy;
| | - Monika Turk
- Deparment of Neurology, University Medical Centre Maribor, 1262 Maribor, Slovenia;
| | - John R. Laird
- Heart and Vascular Institute, Adventist Health St. Helena, St. Helena, CA 94574, USA;
| | - Narendra N. Khanna
- Department of Cardiology, Indraprastha APOLLO Hospitals, New Delhi 110001, India;
| | - Klaudija Viskovic
- Department of Radiology and Ultrasound, University Hospital for Infectious Diseases, 10000 Zagreb, Croatia;
| | - Inder M. Singh
- Stroke Monitoring and Diagnostic Division, AtheroPoint™, Roseville, CA 95661, USA; (A.P.); (I.M.S.)
| | - Mannudeep Kalra
- Department of Radiology, Harvard Medical School, Boston, MA 02115, USA;
| | | | - Amer Johri
- Department of Medicine, Division of Cardiology, Queen’s University, Kingston, ON K7L 3N6, Canada;
| | - Kosmas I. Paraskevas
- Department of Vascular Surgery, Central Clinic of Athens, 106 80 Athens, Greece;
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15
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Fedorowski A, Ricci F, Hamrefors V, Sandau KE, Chung TH, Muldowney JAS, Gopinathannair R, Olshansky B. Orthostatic Hypotension: Management of a Complex, But Common, Medical Problem. Circ Arrhythm Electrophysiol 2022; 15:e010573. [PMID: 35212554 PMCID: PMC9049902 DOI: 10.1161/circep.121.010573] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Orthostatic hypotension (OH), a common, often overlooked, disorder with many causes, is associated with debilitating symptoms, falls, syncope, cognitive impairment, and risk of death. Chronic OH, a cardinal sign of autonomic dysfunction, increases with advancing age and is commonly associated with neurodegenerative and autoimmune diseases, diabetes, hypertension, heart failure, and kidney failure. Management typically involves a multidisciplinary, patient-centered, approach to arrive at an appropriate underlying diagnosis that is causing OH, treating accompanying conditions, and providing individually tailored pharmacological and nonpharmacological treatment. We propose a novel streamlined pathophysiological classification of OH; review the relationship between the cardiovascular disease continuum and OH; discuss OH-mediated end-organ damage; provide diagnostic and therapeutic algorithms to guide clinical decision making and patient care; identify current gaps in knowledge and try to define future research directions. Using a case-based learning approach, specific clinical scenarios are presented highlighting various presentations of OH to provide a practical guide to evaluate and manage patients who have OH.
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Affiliation(s)
- Artur Fedorowski
- Dept of Clinical Sciences, Lund University, Malmö
- Dept of Cardiology, Karolinska University Hospital, Stockholm, Sweden
| | - Fabrizio Ricci
- Dept of Clinical Sciences, Lund University, Malmö
- Dept of Neuroscience, Imaging & Clinical Sciences, “G.d’Annunzio” University, Chieti-Pescara
- Casa di Cura Villa Serena, Città Sant’Angelo, Italy
| | - Viktor Hamrefors
- Dept of Clinical Sciences, Lund University, Malmö
- Dept of Internal Medicine, Skåne University Hospital, Malmö, Sweden
| | | | - Tae Hwan Chung
- Dept of Physical Medicine & Rehabilitation, Johns Hopkins University School of Medicine, Baltimore, MD
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16
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Stock JM, Chelimsky G, Edwards DG, Farquhar WB. Dietary sodium and health: How much is too much for those with orthostatic disorders? Auton Neurosci 2022; 238:102947. [PMID: 35131651 PMCID: PMC9296699 DOI: 10.1016/j.autneu.2022.102947] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 11/09/2021] [Accepted: 01/16/2022] [Indexed: 10/19/2022]
Abstract
High dietary salt (NaCl) increases blood pressure (BP) and can adversely impact multiple target organs including the vasculature, heart, kidneys, brain, autonomic nervous system, skin, eyes, and bone. However, patients with orthostatic disorders are told to increase their NaCl intake to help alleviate symptoms. While there is evidence to support the short-term benefits of increasing NaCl intake in these patients, there are few studies assessing the benefits and side effects of long-term high dietary NaCl. The evidence reviewed suggests that high NaCl can adversely impact multiple target organs, often independent of BP. However, few of these studies have been performed in patients with orthostatic disorders. We conclude that the recommendation to increase dietary NaCl in patients with orthostatic disorders should be done with care, keeping in mind the adverse impact on dietary NaCl in people without orthostatic disorders. Modest, rather than robust, increases in NaCl intake may be sufficient to alleviate symptoms but also minimize any long-term negative effects.
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Affiliation(s)
- Joseph M Stock
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, United States of America
| | - Gisela Chelimsky
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States of America
| | - David G Edwards
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, United States of America
| | - William B Farquhar
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, United States of America.
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17
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Advances in the Pathophysiology and Management of Supine Hypertension in Patients with Neurogenic Orthostatic Hypotension. Curr Hypertens Rep 2022; 24:45-54. [PMID: 35230654 PMCID: PMC9553128 DOI: 10.1007/s11906-022-01168-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/15/2021] [Indexed: 12/21/2022]
Abstract
PURPOSE OF REVIEW Patients with neurogenic orthostatic hypotension (OH) frequently have hypertension in the supine position (sHTN). We review the controversies surrounding the need and safety of treating sHTN in patients with OH. RECENT FINDINGS The presence of sHTN complicates the management of OH because treatment of one can worsen the other. New approaches have been developed to treat OH without worsening sHTN by preferentially improving standing blood pressure, such as medications that harness the patient's residual sympathetic tone like pyridostigmine and atomoxetine, and devices such as an automated abdominal binder that targets the inappropriate splanchnic venous pooling causing OH. There is a reluctance to treat sHTN for fear of increasing the risks of falls and syncope associated with OH, thought to be more immediate and dangerous than the late complications of organ damage associated with sHTN. This, however, does not take into account that nighttime sHTN induces natriuresis, volume loss, and begets daytime orthostatic hypotension. It is possible to treat sHTN in ways that reduce the risk of worsening OH. Furthermore, novel approaches, such as the use of local heat can control nighttime sHTN, reduce nocturia, and improve OH. Although continued progress is needed, recent findings offer hope that we can treat nocturnal sHTN and at the same time improve daytime OH, lessening the controversy whether to treat or not sHTN.
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18
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Sunayama T, Maeda D, Matsue Y, Kagiyama N, Jujo K, Saito K, Kamiya K, Saito H, Ogasawara Y, Maekawa E, Konishi M, Kitai T, Iwata K, Wada H, Hiki M, Dotare T, Kasai T, Nagamatsu H, Ozawa T, Izawa K, Yamamoto S, Aizawa N, Yonezawa R, Oka K, Momomura SI, Minamino T. Prognostic value of postural hypotension in hospitalized patients with heart failure. Sci Rep 2022; 12:2802. [PMID: 35181724 PMCID: PMC8857283 DOI: 10.1038/s41598-022-06760-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 02/04/2022] [Indexed: 11/08/2022] Open
Abstract
Although postural hypotension (PH) is reportedly associated with mortality in the general population, the prognostic value for heart failure is unclear. This was a post-hoc analysis of FRAGILE-HF, a prospective multicenter observational study focusing on frailty in elderly patients with heart failure. Overall, 730 patients aged ≥ 65 years who were hospitalized with heart failure were enrolled. PH was defined by evaluating seated PH, and was defined as a fall of ≥ 20 mmHg in systolic and/or ≥ 10 mmHg in diastolic blood pressure within 3 min after transition from a supine to sitting position. The study endpoints were all-cause death and heart failure readmission at 1 year. Predictive variables for the presence of PH were also evaluated. PH was observed in 160 patients (21.9%). Patients with PH were more likely than those without PH to be male with a New York Heart Association classification of III/IV. Logistic regression analysis showed that male sex, severe heart failure symptoms, and lack of administration of angiotensin-converting enzyme inhibitors were independently associated with PH. PH was not associated with 1-year mortality, but was associated with a lower incidence of readmission after discharge after adjustment for other covariates. In conclusion, PH was associated with reduced risk of heart failure readmission but not with 1-year mortality in older patients with heart failure.
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Affiliation(s)
- Tsutomu Sunayama
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Daichi Maeda
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
- Department of Cardiology, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Yuya Matsue
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
- Cardiovascular Respiratory Sleep Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
| | - Nobuyuki Kagiyama
- Department of Cardiology, The Sakakibara Heart Institute of Okayama, Okayama, Japan
- Department of Digital Health and Telemedicine R&D, Juntendo University, Tokyo, Japan
- Department of Cardiovascular Biology and Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan
| | - Kentaro Jujo
- Department of Cardiology, Nishiarai Heart Center Hospital, Tokyo, Japan
| | - Kazuya Saito
- Department of Rehabilitation, The Sakakibara Heart Institute of Okayama, Okayama, Japan
| | - Kentaro Kamiya
- Department of Rehabilitation, School of Allied Health Sciences, Kitasato University, Sagamihara, Japan
| | - Hiroshi Saito
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
- Department of Rehabilitation, Kameda Medical Center, Kamogawa, Japan
| | - Yuki Ogasawara
- Department of Nursing, The Sakakibara Heart Institute of Okayama, Okayama, Japan
| | - Emi Maekawa
- Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Masaaki Konishi
- Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan
| | - Takeshi Kitai
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
- Department of Rehabilitation, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Kentaro Iwata
- Department of Rehabilitation, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Hiroshi Wada
- Department of Cardiovascular Medicine, Saitama Medical Center, Jichi Medical University, Saitama, Japan
| | - Masaru Hiki
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Taishi Dotare
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Takatoshi Kasai
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
- Cardiovascular Respiratory Sleep Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Hirofumi Nagamatsu
- Department of Cardiology, Tokai University School of Medicine, Isehara, Japan
| | - Tetsuya Ozawa
- Department of Rehabilitation, Odawara Municipal Hospital, Odawara, Japan
| | - Katsuya Izawa
- Department of Rehabilitation, Kasukabe Chuo General Hospital, Kasukabe, Japan
| | - Shuhei Yamamoto
- Department of Rehabilitation, Shinshu University Hospital, Matsumoto, Japan
| | - Naoki Aizawa
- Department of Cardiovascular Medicine, Nephrology and Neurology, University of the Ryukyus, Okinawa, Japan
| | - Ryusuke Yonezawa
- Rehabilitation Center, Kitasato University Medical Center, Kitamoto, Japan
| | - Kazuhiro Oka
- Department of Rehabilitation, Saitama Citizens Medical Center, Saitama, Japan
| | | | - Tohru Minamino
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
- Japan Agency for Medical Research and Development-Core Research for Evolutionary Medical Science and Technology (AMED-CREST), Japan Agency for Medical Research and Development, Tokyo, Japan
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19
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Tanzer TD, Brouard T, Pra SD, Warren N, Barras M, Kisely S, Brooks E, Siskind D. Treatment strategies for clozapine-induced hypotension: a systematic review. Ther Adv Psychopharmacol 2022; 12:20451253221092931. [PMID: 35633931 PMCID: PMC9136453 DOI: 10.1177/20451253221092931] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 03/22/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug effects, including hypotension and dizziness, which have a negative impact on quality of life and treatment compliance. Available evidence for the management of clozapine-induced hypotension is scant. OBJECTIVES Due to limited guidance on the safety and efficacy of pharmacological treatments for clozapine-induced hypotension, we set out to systematically review and assess the evidence for the management of clozapine-induced hypotension and provide guidance to clinicians, patients, and carers. DESIGN We undertook a systematic review of the safety and efficacy of interventions for clozapine-induced hypotension given the limited available evidence. DATA SOURCES AND METHODS PubMed, Embase, PsycINFO, CINAHL, and the Cochrane trial Registry were searched from inception to November 2021 for literature on the treatment strategies for clozapine-induced hypotension and dizziness using a PROSPERO pre-registered search strategy. For orthostatic hypotension, we developed a management framework to assist in the choice of intervention. RESULTS We identified nine case studies and four case series describing interventions in 15 patients. Hypotension interventions included temporary clozapine dose reduction, non-pharmacological treatments, and pharmacological treatments. Midodrine, fludrocortisone, moclobemide and Bovril® combination, and etilefrine were associated with improvement in symptoms or reduction in orthostatic hypotension. Angiotensin II, arginine vasopressin, and noradrenaline successfully restored and maintained mean arterial pressure in critical care situations. A paradoxical reaction of severe hypotension was reported with adrenaline use. CONCLUSION Orthostatic hypotension is a common side effect during clozapine titration. Following an assessment of the titration schedule, salt and fluid intake, and review of hypertensive and nonselective α1-adrenergic agents, first-line treatment should be a temporary reduction in clozapine dose or non-pharmacological interventions. If orthostatic hypotension persists, fludrocortisone should be trialled with monitoring of potassium levels and sodium and fluid intake. Midodrine may be considered second-line or where fludrocortisone is contraindicated or poorly tolerated. For patients on clozapine with hypotension in critical care settings, the use of adrenaline to maintain mean arterial pressure should be avoided. REGISTRATION PROSPERO (Registration No. CRD42020191530).
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Affiliation(s)
| | - Thomas Brouard
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Samuel Dal Pra
- Metro South Addiction and Mental Health Services, Brisbane, QLD, Australia
| | - Nicola Warren
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Michael Barras
- Department of Pharmacy, Princess Alexandra Hospital, Brisbane, QLD, Australia School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia
| | - Steve Kisely
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Emily Brooks
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Dan Siskind
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
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20
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De Gioannis R, Ewald AC, Gerlach DA, Heusser K, Hoffmann F, Frings-Meuthen P, Heer M, Tank J, Jordan J. Effects of short-term hypercaloric nutrition on orthostatic tolerance in healthy individuals: a randomized controlled crossover study. Clin Auton Res 2022; 32:423-430. [PMID: 36195683 PMCID: PMC9719449 DOI: 10.1007/s10286-022-00900-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 09/21/2022] [Indexed: 01/31/2023]
Abstract
Reduced-caloric intake lowers blood pressure through sympathetic inhibition, and worsens orthostatic tolerance within days. Conversely, hypercaloric nutrition augments sympathetic activity and blood pressure. Because dietary interventions could be applied in patients with syncope, we tested the hypothesis that short-term hypercaloric dieting improves orthostatic tolerance. In a randomized crossover trial, 20 healthy individuals (7 women, 26.7 ± 8 years, 22.6 ± 2 kg/m2) followed a 4-day hypercaloric (25% increase of energy intake by fat) or normocaloric nutritional plan, with a washout period of at least 23 days between interventions. We then performed head-up tilt table testing with incremental lower body negative pressure while recording beat-by-beat blood pressure and heart rate. The primary endpoint was orthostatic tolerance defined as time to presyncope. Time to presyncope during combined head-up tilt and lower body negative pressure did not differ between hypercaloric and normocaloric dieting (median 23.19 versus 23.04 min, ratio of median 1.01, 95% CI of ratio 0.5-1.9). Heart rate, blood pressure, heart rate variability, and blood pressure variability in the supine position and during orthostatic testing did not differ between interventions. We conclude that 4 days of moderate hypercaloric nutrition does not significantly improve orthostatic tolerance in healthy individuals. Nevertheless, given the important interaction between energy balance and cardiovascular autonomic control in the brain, caloric intake deserves more attention as a potential contributor and treatment target for orthostatic intolerance.
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Affiliation(s)
- Riccardo De Gioannis
- Institute of Aerospace Medicine, German Aerospace Center (DLR), Linder Hoehe, 51147, Cologne, Germany
- Faculty of Medicine, Department III for Internal Medicine, Heart Center, University Hospital of Cologne, Cologne, Germany
| | - Ann C Ewald
- Institute of Aerospace Medicine, German Aerospace Center (DLR), Linder Hoehe, 51147, Cologne, Germany
| | - Darius A Gerlach
- Institute of Aerospace Medicine, German Aerospace Center (DLR), Linder Hoehe, 51147, Cologne, Germany
| | - Karsten Heusser
- Institute of Aerospace Medicine, German Aerospace Center (DLR), Linder Hoehe, 51147, Cologne, Germany
| | - Fabian Hoffmann
- Institute of Aerospace Medicine, German Aerospace Center (DLR), Linder Hoehe, 51147, Cologne, Germany
- Faculty of Medicine, Department III for Internal Medicine, Heart Center, University Hospital of Cologne, Cologne, Germany
| | - Petra Frings-Meuthen
- Institute of Aerospace Medicine, German Aerospace Center (DLR), Linder Hoehe, 51147, Cologne, Germany
| | - Martina Heer
- IU International University of Applied Sciences, Erfurt, Germany
| | - Jens Tank
- Institute of Aerospace Medicine, German Aerospace Center (DLR), Linder Hoehe, 51147, Cologne, Germany
| | - Jens Jordan
- Institute of Aerospace Medicine, German Aerospace Center (DLR), Linder Hoehe, 51147, Cologne, Germany.
- Chair of Aerospace Medicine, University of Cologne, Cologne, Germany.
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21
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Zhu S, Li H, Xu X, Luo Y, Deng B, Guo X, Guo Y, Yang W, Wei X, Wang Q. The Pathogenesis and Treatment of Cardiovascular Autonomic Dysfunction in Parkinson's Disease: What We Know and Where to Go. Aging Dis 2021; 12:1675-1692. [PMID: 34631214 PMCID: PMC8460297 DOI: 10.14336/ad.2021.0214] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 02/14/2021] [Indexed: 12/15/2022] Open
Abstract
Cardiovascular autonomic dysfunctions (CAD) are prevalent in Parkinson’s disease (PD). It contributes to the development of cognitive dysfunction, falls and even mortality. Significant progress has been achieved in the last decade. However, the underlying mechanisms and effective treatments for CAD have not been established yet. This review aims to help clinicians to better understand the pathogenesis and therapeutic strategies. The literatures about CAD in patients with PD were reviewed. References for this review were identified by searches of PubMed between 1972 and March 2021, with the search term “cardiovascular autonomic dysfunctions, postural hypotension, orthostatic hypotension (OH), supine hypertension (SH), postprandial hypotension, and nondipping”. The pathogenesis, including the neurogenic and non-neurogenic mechanisms, and the current pharmaceutical and non-pharmaceutical treatment for CAD, were analyzed. CAD mainly includes four aspects, which are OH, SH, postprandial hypotension and nondipping, among them, OH is the main component. Both non-neurogenic and neurogenic mechanisms are involved in CAD. Failure of the baroreflex circulate, which includes the lesions at the afferent, efferent or central components, is an important pathogenesis of CAD. Both non-pharmacological and pharmacological treatment alleviate CAD-related symptoms by acting on the baroreflex reflex circulate. However, pharmacological strategy has the limitation of failing to enhance baroreflex sensitivity and life quality. Novel OH treatment drugs, such as pyridostigmine and atomoxetine, can effectively improve OH-related symptoms via enhancing residual sympathetic tone, without adverse reactions of supine hypertension. Baroreflex impairment is a crucial pathological mechanism associated with CAD in PD. Currently, non-pharmacological strategy was the preferred option for its advantage of enhancing baroreflex sensitivity. Pharmacological treatment is a second-line option. Therefore, to find drugs that can enhance baroreflex sensitivity, especially via acting on its central components, is urgently needed in the scientific research and clinical practice.
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Affiliation(s)
- Shuzhen Zhu
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Hualing Li
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Xiaoyan Xu
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Yuqi Luo
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Bin Deng
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Xingfang Guo
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Yang Guo
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Wucheng Yang
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Xiaobo Wei
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Qing Wang
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
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22
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Pirooznia SK, Rosenthal LS, Dawson VL, Dawson TM. Parkinson Disease: Translating Insights from Molecular Mechanisms to Neuroprotection. Pharmacol Rev 2021; 73:33-97. [PMID: 34663684 DOI: 10.1124/pharmrev.120.000189] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Parkinson disease (PD) used to be considered a nongenetic condition. However, the identification of several autosomal dominant and recessive mutations linked to monogenic PD has changed this view. Clinically manifest PD is then thought to occur through a complex interplay between genetic mutations, many of which have incomplete penetrance, and environmental factors, both neuroprotective and increasing susceptibility, which variably interact to reach a threshold over which PD becomes clinically manifested. Functional studies of PD gene products have identified many cellular and molecular pathways, providing crucial insights into the nature and causes of PD. PD originates from multiple causes and a range of pathogenic processes at play, ultimately culminating in nigral dopaminergic loss and motor dysfunction. An in-depth understanding of these complex and possibly convergent pathways will pave the way for therapeutic approaches to alleviate the disease symptoms and neuroprotective strategies to prevent disease manifestations. This review is aimed at providing a comprehensive understanding of advances made in PD research based on leveraging genetic insights into the pathogenesis of PD. It further discusses novel perspectives to facilitate identification of critical molecular pathways that are central to neurodegeneration that hold the potential to develop neuroprotective and/or neurorestorative therapeutic strategies for PD. SIGNIFICANCE STATEMENT: A comprehensive review of PD pathophysiology is provided on the complex interplay of genetic and environmental factors and biologic processes that contribute to PD pathogenesis. This knowledge identifies new targets that could be leveraged into disease-modifying therapies to prevent or slow neurodegeneration in PD.
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Affiliation(s)
- Sheila K Pirooznia
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering (S.K.P., V.L.D., T.M.D.), Departments of Neurology (S.K.P., L.S.R., V.L.D., T.M.D.), Departments of Physiology (V.L.D.), Solomon H. Snyder Department of Neuroscience (V.L.D., T.M.D.), Department of Pharmacology and Molecular Sciences (T.M.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana (S.K.P., V.L.D., T.M.D.); and Diana Helis Henry Medical Research Foundation, New Orleans, Louisiana (S.K.P., V.L.D., T.M.D.)
| | - Liana S Rosenthal
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering (S.K.P., V.L.D., T.M.D.), Departments of Neurology (S.K.P., L.S.R., V.L.D., T.M.D.), Departments of Physiology (V.L.D.), Solomon H. Snyder Department of Neuroscience (V.L.D., T.M.D.), Department of Pharmacology and Molecular Sciences (T.M.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana (S.K.P., V.L.D., T.M.D.); and Diana Helis Henry Medical Research Foundation, New Orleans, Louisiana (S.K.P., V.L.D., T.M.D.)
| | - Valina L Dawson
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering (S.K.P., V.L.D., T.M.D.), Departments of Neurology (S.K.P., L.S.R., V.L.D., T.M.D.), Departments of Physiology (V.L.D.), Solomon H. Snyder Department of Neuroscience (V.L.D., T.M.D.), Department of Pharmacology and Molecular Sciences (T.M.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana (S.K.P., V.L.D., T.M.D.); and Diana Helis Henry Medical Research Foundation, New Orleans, Louisiana (S.K.P., V.L.D., T.M.D.)
| | - Ted M Dawson
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering (S.K.P., V.L.D., T.M.D.), Departments of Neurology (S.K.P., L.S.R., V.L.D., T.M.D.), Departments of Physiology (V.L.D.), Solomon H. Snyder Department of Neuroscience (V.L.D., T.M.D.), Department of Pharmacology and Molecular Sciences (T.M.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana (S.K.P., V.L.D., T.M.D.); and Diana Helis Henry Medical Research Foundation, New Orleans, Louisiana (S.K.P., V.L.D., T.M.D.)
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23
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Do T, Diamond S, Green C, Warren M. Nutritional Implications of Patients with Dysautonomia and Hypermobility Syndromes. Curr Nutr Rep 2021; 10:324-333. [PMID: 34510391 PMCID: PMC8435108 DOI: 10.1007/s13668-021-00373-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/17/2021] [Indexed: 09/04/2024]
Abstract
PURPOSE OF REVIEW Dysautonomia and hypermobility syndrome are two distinct but often overlapping clinical conditions that are recognized for their complex multiorgan system afflictions. The purpose of this review is to investigate dietary strategies to reduce symptoms and augment quality of life in this growing patient population. RECENT FINDINGS There is increasing evidence supporting dietary modifications to include food rich in probiotics and prebiotics, along with fiber supplements to reduce gastrointestinal symptoms. Adequate salt and fluid intake may reduce orthostatic hypotension symptoms. Dietary supplements may help with osteoarticular, musculoskeletal, and fatigue symptoms. Individualized diet strategies and supplements can reduce the multiorgan system symptoms observed in dysautonomia and hypermobility syndrome.
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Affiliation(s)
- Toan Do
- Internal Medicine, Oregon Health & Science University, Portland, OR, USA.
| | - Sarah Diamond
- Division of Gastroenterology & Hepatology, Oregon Health & Science University, Portland, OR, USA
| | - Caitlin Green
- Division of Gastroenterology & Hepatology, Medical University of South Carolina, Charleston, SC, USA
| | - Malissa Warren
- Department of Surgery, Oregon Health & Science University, Portland, OR, USA.
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24
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Abstract
Advanced Parkinson disease (PD) is associated with treatment-related motor fluctuations and reduced ability to perform activities of daily living. Progression of non-motor symptoms and medication-induced adverse effects complicate focused approach to motor symptom management, frequently accelerating reduced quality of life. It is thus critical for clinicians to consider disease progression versus therapeutic contributions when balancing management decisions. Such an approach requires careful recognition of inflection points resulting from therapeutic decisions and should prompt consideration of reduced pharmacologic burden and increased reliance on non-pharmacologic strategies in advanced disease. The successful approach to advanced PD requires a multidisciplinary effort focused on improving the patient's and family's quality of life, sometimes requiring sacrifice of motor symptom benefit. Here, we emphasize management strategies in advanced PD, focusing on the need to balance the therapeutic approach across advancing motor symptoms, progressive non-motor features, and potential pharmacologic adverse effects.
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Affiliation(s)
- Helen Hwang
- Department of Neurology, 7548Washington University School of Medicine, St Louis, MO, USA
| | - Scott A Norris
- Department of Neurology, 7548Washington University School of Medicine, St Louis, MO, USA
- Department of Radiology, 7548Washington University School of Medicine, St Louis, MO, USA
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25
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Rocha EA, Mehta N, Távora-Mehta MZP, Roncari CF, Cidrão AADL, Elias Neto J. Dysautonomia: A Forgotten Condition - Part II. Arq Bras Cardiol 2021; 116:981-998. [PMID: 34008826 PMCID: PMC8121459 DOI: 10.36660/abc.20200422] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 11/04/2020] [Indexed: 12/15/2022] Open
Affiliation(s)
- Eduardo Arrais Rocha
- Hospital Universitário Walter Cantídio da Universidade Federal do Ceará (UFC) - Programa de Pós-graduação em Ciências Cardiovasculares da Faculdade de Medicina da UFC, Fortaleza, CE - Brasil
| | - Niraj Mehta
- Universidade Federal do Paraná, Curitiba, PR - Brasil.,Clínica de Eletrofisiologia do Paraná, Curitiba, PR - Brasil
| | | | - Camila Ferreira Roncari
- Departamento de Fisiologia e Farmacologia - Faculdade de Medicina da Universidade Federal do Ceará (UFC), Fortaleza, CE - Brasil
| | - Alan Alves de Lima Cidrão
- Programa de Pós-graduação em Ciências Cardiovasculares da Faculdade de Medicina da UFC, Fortaleza, CE - Brasil
| | - Jorge Elias Neto
- Serviço de Eletrofisiologia do Vitória Apart Hospital, Vitória, ES - Brasil
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26
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Katsi V, Papakonstantinou I, Solomou E, Antonopoulos AS, Vlachopoulos C, Tsioufis K. Management of Hypertension and Blood Pressure Dysregulation in Patients with Parkinson's Disease-a Systematic Review. Curr Hypertens Rep 2021; 23:26. [PMID: 33961147 DOI: 10.1007/s11906-021-01146-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/16/2021] [Indexed: 12/17/2022]
Abstract
PURPOSE OF REVIEW The aim of this review article was to summarize the cardiovascular and blood pressure profile regarding Parkinson disease patients and to provide an update on the recent advancements in the field of the diagnosis and management of blood pressure abnormalities in these patients. Our goal was to guide physicians to avoid pitfalls in current practice while treating patients with Parkinson disease and blood pressure abnormalities. For this purpose, we searched bibliographic databases (PubMed, Google Scholar) for all publications published on blood pressure effects in Parkinson disease until May 2020. Furthermore, we highlight some thoughts and potential perspectives for the next possible steps in the field. RECENT FINDINGS Blood pressure dysregulation in patients with Parkinson's disease has several implications in clinical practice and presents an ongoing concern. Compared with chronic essential hypertension, the syndrome of combined neurogenic orthostatic hypotension and supine hypertension in Parkinson's disease has received little attention. If left untreated, hypertension may lead to cardiovascular disease whereas hypotension may lead to fall-related complications, with tremendous impact on the quality of life of affected individuals. The effect of blood Epressure control and the risk of death from cardiovascular disease in Parkinson disease are largely unexplored. Blood pressure abnormalities in Parkinson disease present bidirectional relationship and the rationale for treating and controlling hypertension in persons with Parkinson disease and concurrent neurogenic orthostatic hypotension and/or supine hypertension is compelling. Further research is warranted in order to clarify the mechanisms, clinical implications, and potential reversibility of compromised cardiovascular function, in persons with Parkinson disease.
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Affiliation(s)
- Vasiliki Katsi
- Cardiology Department, Hippokration General Hospital, Athens, Greece. .,Internal Medicine, Evangelismos Hospital, Athens, Greece.
| | - Ilias Papakonstantinou
- Cardiology Department, Hippokration General Hospital, Athens, Greece.,Internal Medicine, Evangelismos Hospital, Athens, Greece
| | - Eirini Solomou
- Cardiology Department, Hippokration General Hospital, Athens, Greece.,Internal Medicine, Evangelismos Hospital, Athens, Greece
| | - Alexios S Antonopoulos
- Cardiology Department, Hippokration General Hospital, Athens, Greece.,Internal Medicine, Evangelismos Hospital, Athens, Greece
| | - Charalambos Vlachopoulos
- Cardiology Department, Hippokration General Hospital, Athens, Greece.,Internal Medicine, Evangelismos Hospital, Athens, Greece
| | - Konstantinos Tsioufis
- Cardiology Department, Hippokration General Hospital, Athens, Greece.,Internal Medicine, Evangelismos Hospital, Athens, Greece
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27
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Christopoulos EM, Tran J, Hillebrand SL, Lange PW, Iseli RK, Meskers CGM, Maier AB. Initial orthostatic hypotension and orthostatic intolerance symptom prevalence in older adults: A systematic review. Int J Cardiol Hypertens 2021; 8:100071. [PMID: 33884364 PMCID: PMC7803043 DOI: 10.1016/j.ijchy.2020.100071] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 11/13/2020] [Accepted: 12/04/2020] [Indexed: 11/25/2022] Open
Abstract
Background Initial orthostatic hypotension is a clinically relevant syndrome in older adults which has been associated with symptoms of orthostatic intolerance. The aim of this systematic review was to determine the prevalence of orthostatic intolerance symptoms in older adults with initial orthostatic hypotension. Methods MEDLINE (from 1946), EMBASE (from 1974) and Cochrane were searched to December 6th, 2019 using the terms "initial orthostatic hypotension", "postural hypotension" and "older adults". Study selection involved the following criteria: published in English; mean or median age ≥ 65 years and diagnosis of initial orthostatic hypotension encompassed a decrease in systolic blood pressure by ≥ 40 mmHg and/or diastolic blood pressure by ≥ 20 mmHg within a maximum of 1 min following a postural change. Results Of 8311 articles, 12 articles reporting initial orthostatic hypotension prevalence in 3446 participants with a mean age of 75 (6 SD) years (56.5% female) were included. Five initial orthostatic hypotension definition variations were utilised and symptoms were reported in six articles (968 participants, mean age 73.4 (6.1 SD) years, 56% female). The prevalence of symptoms in older adults with initial orthostatic hypotension ranged from 24 to 100% and was dependent on variations in timing or the inclusion of symptoms in the initial orthostatic hypotension definition. Conclusions Where orthostatic intolerance symptoms were reported, a large proportion of older adults with a diagnosis of initial orthostatic hypotension were symptomatic. However, the literature on initial orthostatic hypotension and orthostatic intolerance symptoms is scarce and a variety of definitions of initial orthostatic hypotension are utilised.
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Affiliation(s)
- Elena M Christopoulos
- Department of Medicine and Aged Care, @AgeMelbourne, The Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia
| | - Jennifer Tran
- Department of Medicine and Aged Care, @AgeMelbourne, The Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia
| | - Sarah L Hillebrand
- Department of Human Movement Sciences, @AgeAmsterdam, Faculty of Behavioural and Movement Sciences, VU University Amsterdam, Amsterdam Movement Sciences, Amsterdam, the Netherlands
| | - Peter W Lange
- Department of Medicine and Aged Care, @AgeMelbourne, The Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia
| | - Rebecca K Iseli
- Department of Medicine and Aged Care, @AgeMelbourne, The Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia
| | - Carel G M Meskers
- Department of Rehabilitation Medicine, Amsterdam UMC, VU University Medical Center, Amsterdam Movement Sciences, Amsterdam, the Netherlands
| | - Andrea B Maier
- Department of Medicine and Aged Care, @AgeMelbourne, The Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia.,Department of Human Movement Sciences, @AgeAmsterdam, Faculty of Behavioural and Movement Sciences, VU University Amsterdam, Amsterdam Movement Sciences, Amsterdam, the Netherlands
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28
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Logan A, Freeman J, Pooler J, Kent B, Gunn H, Billings S, Cork E, Marsden J. Effectiveness of non-pharmacological interventions to treat orthostatic hypotension in elderly people and people with a neurological condition: a systematic review. JBI Evid Synth 2021; 18:2556-2617. [PMID: 32773495 DOI: 10.11124/jbisrir-d-18-00005] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
OBJECTIVE The objective of this review was to summarize the best available evidence regarding the effectiveness of non-pharmacological interventions to treat orthostatic hypotension (OH) in elderly people and people with a neurological condition. INTRODUCTION Orthostatic hypotension is common in elderly people and people with a neurological condition and can interfere with or limit rehabilitation. Non-pharmacological interventions to treat OH could allow for longer and earlier mobilization, which is recommended in national clinical guidelines for rehabilitation in the acute or sub-acute phase following stroke or other neurological conditions. INCLUSION CRITERIA The review considered people aged 50 years and older, and people aged 18 years and elderly people with a neurological condition. Non-pharmacological interventions to treat OH included compression garments, neuromuscular stimulation, physical counter-maneuvers, aerobic or resistance exercises, sleeping with head tilted up, increasing fluid and salt intake, and timing and size of meals. The comparator was usual care, no intervention, pharmacological interventions, or other non-pharmacological interventions. Outcome measures included systolic blood pressure, diastolic blood pressure, heart rate, cerebral blood flow, observed/perceived symptoms, duration of standing or sitting in minutes, tolerance of therapy, functional ability, and adverse events/effects. METHODS Databases for published and unpublished studies available in English up to April 2018 with no lower date limit were searched. Critical appraisal was conducted using standardized instruments from JBI. Data were extracted using standardized tools designed for quantitative studies. Where appropriate, studies were included in a meta-analysis; otherwise, data were presented in a narrative form due to heterogeneity. RESULTS Forty-three studies - a combination of randomized controlled trials (n = 13), quasi-experimental studies (n = 28), a case control study (n = 1), and a case report (n = 1) - with 1069 participants were included. Meta-analyses of three interventions (resistance exercise, electrical stimulation, and lower limb compression bandaging) showed no significant effect of these interventions. Results from individual studies indicated physical maneuvers such as leg crossing, leg muscle pumping/contractions, and bending forward improved orthostatic hypotension. Abdominal compression improved OH. Sleeping with head up in combination with pharmacological treatment was more effective than sleeping with head up alone. Eating smaller, more frequent meals was effective. Drinking 480 mL of water increased blood pressure. CONCLUSIONS The review found mixed results for the effectiveness of non-pharmacological interventions to treat OH in people aged 50 years and older, and people with a neurological condition. There are several non-pharmacological interventions that may be effective in treating OH, but not all have resulted in clinically meaningful changes in outcome. Some may not be suitable for people with moderate to severe disability; therefore, it is important for clinicians to consider the patient's abilities and impairments when considering which non-pharmacological interventions to implement.
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Affiliation(s)
- Angela Logan
- School of Health Professions, Faculty of Health, Peninsula Allied Health Centre, Plymouth University, Plymouth, UK.,Stroke and Neurology Therapy Team, Cornwall Partnership Foundation NHS Trust, Camborne Redruth Community Hospital, Cornwall, UK.,The University of Plymouth Centre for Innovations in Health and Social Care: A JBI Centre of Excellence
| | - Jennifer Freeman
- School of Health Professions, Faculty of Health, Peninsula Allied Health Centre, Plymouth University, Plymouth, UK.,The University of Plymouth Centre for Innovations in Health and Social Care: A JBI Centre of Excellence
| | - Jillian Pooler
- Faculty of Health, Peninsula Medical and Dentistry Schools, Plymouth, UK
| | - Bridie Kent
- The University of Plymouth Centre for Innovations in Health and Social Care: A JBI Centre of Excellence.,School of Nursing and Midwifery, Faculty of Health, Plymouth University, Plymouth, UK
| | - Hilary Gunn
- School of Health Professions, Faculty of Health, Peninsula Allied Health Centre, Plymouth University, Plymouth, UK
| | - Sarah Billings
- Stroke Rehabilitation Unit, Livewell Southwest, Mount Gould Hospital, Plymouth, UK
| | - Emma Cork
- Stroke Rehabilitation Department, Northern Devon Healthcare Trust, Northern Devon District Hospital, Barnstaple, UK
| | - Jonathan Marsden
- School of Health Professions, Faculty of Health, Peninsula Allied Health Centre, Plymouth University, Plymouth, UK.,The University of Plymouth Centre for Innovations in Health and Social Care: A JBI Centre of Excellence
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29
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Abstract
PURPOSE OF REVIEW Cardiovascular autonomic dysfunction (AD) among cancer survivors is increasingly being recognized. However, the mechanisms and incidence are poorly understood. In this review, the clinical features, diagnostic modalities, proposed mechanisms, and currently available treatments of cardiovascular AD in cancer survivors are described. RECENT FINDINGS Much of our current understanding of cardiovascular AD is based on disease states such as diabetes, multisystem atrophy, and Parkinson's disease. Several non-invasive tests, measurements, and scoring systems have been developed as surrogates for autonomic function, with some even demonstrating associations with all-cause mortality. The mechanism of cardiovascular AD specifically in the cancer population, however, has not been directly studied. The etiology of cardiovascular AD in cancer survivors is likely multifactorial, and proposed mechanisms include direct nerve damage by chemoradiation, the pro-inflammatory state associated with malignancy, and paraneoplastic syndromes. It may also be that cardiovascular AD is an early marker of global cardiomyopathy rather than its own condition. Current pharmacologic options for cardiovascular AD are extrapolated from how it has been treated in other disease processes, and these agents have not been studied in the cancer population or compared head-to-head. Cardiovascular AD in cancer survivors can cause significant debilitation and may be associated with all-cause mortality. Current diagnostic modalities have several limitations, such as standardization and validity. However, given the nonspecific nature of cardiovascular AD, these tools provide an objective marker for diagnosis and tracking treatment response. While the mechanism of cardiovascular AD in cancer survivors has not been directly studied, it may be useful to evoke mechanisms of cardiovascular AD in other disease states such as diabetes, Parkinson's disease, and multisystem atrophy in addition to identifying unique conditions associated with malignancy like a pro-inflammatory state. Until further studies are performed, management of cardiovascular AD as seen in other disease states may serve as a guide for symptom management in cancer survivors.
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30
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A Case Report of Pediatric Paraneoplastic Dysautonomia. Pediatr Emerg Care 2020; 36:e742-e744. [PMID: 30045352 DOI: 10.1097/pec.0000000000001558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
We present the case of a 16-year-old girl who presented with severe refractory orthostatic hypotension secondary to pandysautonomia. Initially, she was treated for Guillain-Barré syndrome given clinical symptoms and increased protein on cerebrospinal fluid, but the severity of symptoms and lack of response to intravenous immunoglobulin prompted further evaluation for an autoimmune etiology. She was ultimately diagnosed with paraneoplastic neuropathy secondary to Hodgkin lymphoma. Paraneoplastic neurologic phenomena are rare, occurring in just 0.01% of cancers, and prompt recognition is crucial for initiating appropriate therapy. Rapid progression of severe disabling symptoms should raise suspicion for an underlying malignancy. The patient had limited response to splanchnic vasoconstrictors in addition to α-agonists, anticholinergics, and mineralocorticoids until initiation of modified Hodgkin lymphoma directed chemotherapy plus rituximab.
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31
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Li L, Li H, He L, Chen H, Li Y. Study on the Relationship Between Orthostatic Hypotension and Heart Rate Variability, Pulse Wave Velocity Index, and Frailty Index in the Elderly: A Retrospective Observational Study. Front Cardiovasc Med 2020; 7:603957. [PMID: 33330668 PMCID: PMC7728663 DOI: 10.3389/fcvm.2020.603957] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 10/27/2020] [Indexed: 11/13/2022] Open
Abstract
Background: Orthostatic hypotension (OH) is a common disease of the elderly. It is generally believed that the pathogenesis of OH is related to the impairment of autonomic nerve function and the decreased vascular capacity regulation. This study aims to explore the relationship between OH and heart rate variability (HRV) parameters, which reflects autonomic nerve function; ankle-brachial pressure index (ABI), which reflects the degree of vascular stenosis; pulse wave velocity (PWV) index, which reflects vascular stiffness; and frailty index (FI), which reflects the overall health status of the elderly. Methods: From January to September 2018, 24-h HOLTER monitoring, PWV, and ABI were performed in 108 elderly patients with OH and 64 elderly patients who underwent physical examination in our hospital. Analysis software was used to record the subject's standard deviation of the cardiac cycle (SDNN), the standard deviation of the 5-min average cardiac cycle (SDANN), the square root of the average square sum of consecutive n-interval differences (rMSSD), the percentage of the number of adjacent cardiac interval differences >50 ms (pNN50), low frequency (LF), high frequency (HF), very low frequency (VLF), and low frequency/high frequency ratio (LF/HF). Then, FI was evaluated qualitatively and quantitatively in the form of a scale. Results: There was no statistical difference between the two groups on the basis of age, sex, body mass index (BMI), low-density lipoprotein (LDL), resting heart rate, blood pressure, fasting blood glucose, long-term medication, etc. There were significant differences in PWV, SDNN, LF, VLF, and LF/HF between the two groups (P < 0.05). The risk factor of OH in the qualitative (P = 0.04) and quantitative (P = 0.007) index FI was higher in the OH group than in the control group. The risk factors of OH were PWV, SDNN, VLF, LF/HF, and FI, where FI was positively correlated and LF/HF was negatively correlated. Conclusions: The pathogenesis of OH is related to vascular stiffness, imbalance of autonomic nerve regulation, and its comprehensive health status in the elderly. However, arteriosclerosis has not been confirmed as an independent risk factor. Clinical Trial Registration: Retrospectively registered, http://www.chictr.org.cn.
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Affiliation(s)
- Lun Li
- Department of Cardiology, Tongji Medical College, Wuhan Fourth Hospital, Puai Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Huanhuan Li
- Department of Cardiology, Tongji Medical College, Wuhan Fourth Hospital, Puai Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Li He
- Department of Cardiology, Tongji Medical College, Wuhan Fourth Hospital, Puai Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Hongyan Chen
- Department of Physical Examination, Tongji Medical College, Wuhan Fourth Hospital, Puai Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Yunqiao Li
- Department of Geriatrics, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
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Nardone R, Höller Y, Brigo F, Versace V, Sebastianelli L, Florea C, Schwenker K, Golaszewski S, Saltuari L, Trinka E. Spinal cord involvement in Lewy body-related α-synucleinopathies. J Spinal Cord Med 2020; 43:832-845. [PMID: 30620687 PMCID: PMC7808259 DOI: 10.1080/10790268.2018.1557863] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022] Open
Abstract
Context: Lewy body (LB)-related α-synucleinopathy (LBAS) is the neuropathological hallmark of several neurodegenerative diseases such as Parkinson disease (PD), but it is also found in neurologically asymptomatic subjects. An abnormal accumulation of α-synuclein has been reported also in the spinal cord, but extent and significance of the spinal cord involvement are still poorly defined. Objective: We aimed to review the studies addressing the spinal cord involvement of LBAS in healthy subjects and in patients with PD or other neurodegenerative diseases. Methods: A MEDLINE search was performed using following terms: "spinal cord", " α-synucleinopathy", "α-synuclein", "Lewy body", "Parkinson's disease", "multiple system atrophy", "neurodegenerative disorder". Results: LBAS in the spinal cord is associated with that of the medullary reticular formation and locus ceruleus in the brainstem but not with that in the olfactory bulb and amygdala. The intermediolateral columns of the thoracic and sacral cord are the most frequently and severely affected region of the spinal cord. LBAS occurs in centrally projecting spinal cord neurons integrating pain, in particular from lower body periphery. It also involves the sacral parasympathetic nucleus innervating the smooth muscles of the bladder and distal colon and the Onuf's nucleus innervating the striated sphincters. The spinal cord lesions may thus play a crucial role in the genesis of frequent non-motor symptoms such as pain, urinary symptoms, bowel dysfunction, autonomic failure including orthostatic hypotension and sexual disturbances. Moreover, these may also contribute to the motor symptoms, since α-synuclein inclusions have been observed in the pyramidal tracts of patients with PD and multiple system atrophy. Conclusion: Recognition of this peculiar spinal cord pathology may help in the management of the related symptoms in subjects affected by α-synucleinopathies.
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Affiliation(s)
- Raffaele Nardone
- Department of Neurology, Franz Tappeiner Hospital, Merano, Italy,Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria,Spinal Cord Injury and Tissue Regeneration Center, Salzburg, Austria,Karl Landsteiner Institut für Neurorehabilitation und Raumfahrtneurologie, Salzburg, Austria,Correspondence to: Dr. Raffaele Nardone, Department of Neurology, “F. Tappeiner” Hospital, Merano, Via Rossini, Merano, BZ 5 39012, Italy; Ph: 0473/264616, 0473/264449. Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/yscm
| | - Yvonne Höller
- Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria
| | - Francesco Brigo
- Department of Neurology, Franz Tappeiner Hospital, Merano, Italy,Department of Neuroscience, Biomedicine and Movement Science, University of Verona, Verona, Italy
| | - Viviana Versace
- Department of Neurorehabilitation, Hospital of Vipiteno, Vipiteno, Italy,Research Unit for Neurorehabilitation South Tyrol, Bolzano, Italy
| | - Luca Sebastianelli
- Department of Neurorehabilitation, Hospital of Vipiteno, Vipiteno, Italy,Research Unit for Neurorehabilitation South Tyrol, Bolzano, Italy
| | - Cristina Florea
- Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria
| | - Kerstin Schwenker
- Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria,Karl Landsteiner Institut für Neurorehabilitation und Raumfahrtneurologie, Salzburg, Austria
| | - Stefan Golaszewski
- Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria,Karl Landsteiner Institut für Neurorehabilitation und Raumfahrtneurologie, Salzburg, Austria
| | - Leopold Saltuari
- Department of Neurorehabilitation, Hospital of Vipiteno, Vipiteno, Italy,Research Unit for Neurorehabilitation South Tyrol, Bolzano, Italy,Department of Neurology, Hochzirl Hospital, Zirl, Austria
| | - Eugen Trinka
- Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria,Spinal Cord Injury and Tissue Regeneration Center, Salzburg, Austria,Centre for Cognitive Neurosciences Salzburg, Salzburg, Austria,University for Medical Informatics and Health Technology, UMIT, Hall in Tirol, Austria
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Li X, Shi R, Meng Q, Zhang X, Chen X. Does arterial stiffness affect orthostatic hypotension among high-altitude Tibetans? Postgrad Med 2020; 133:173-180. [PMID: 32926805 DOI: 10.1080/00325481.2020.1823683] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVE This study aimed to investigate the association between arterial stiffness and orthostatic hypotension (OH) and orthostatic blood pressure (BP) changes among Tibetans living at high altitude. METHODS A total of 630 high-altitude Tibetans were included (56.53 ± 10.16 years; 246 men). Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). OH was defined as a decrease in systolic BP (SBP) >20 mmHg or a decrease in diastolic BP (DBP) >10 mmHg after 1 min or 3 min of moving from supine to standing position. RESULTS The prevalence of OH in this population was 6.3%. Compared with subjects without OH, the subjects with OH had a higher baPWV (P < 0.001). Multiple logistical regression found that baPWV was significantly associated with the occurrence of OH (OR 1.147, CI 95% 1.028-1.280, P = 0.014). Spearman correlation analysis showed that baPWV was negatively associated with orthostatic changes in SBP and DBP(r = -0.256, P < 0.001 and r = -0.194, P < 0.001, respectively). Further multiple stepwise linear regression analysis showed that baPWV was independently correlated with orthostatic BP changes (SBP: β = -0.599, P < 0.001; DBP: β = -0.333, P < 0.001). Moreover, increased baPWV was correlated with attenuation of orthostatic heart rate changes. No significant association was observed between hematocrit or hemoglobin concentration and OH. CONCLUSION BaPWV was significantly associated with the occurrence of OH and orthostatic changes in the SBP and DBP, which suggests that arterial stiffness may be a potential mechanism of impaired hemodynamic response to orthostatic challenges among high-altitude Tibetans.
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Affiliation(s)
- Xinran Li
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Rufeng Shi
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Qingtao Meng
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xin Zhang
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiaoping Chen
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Ortiz JF, Betté S, Tambo W, Tao F, Cozar JC, Isaacson S. Multiple System Atrophy - Cerebellar Type: Clinical Picture and Treatment of an Often-Overlooked Disorder. Cureus 2020; 12:e10741. [PMID: 33173654 PMCID: PMC7645310 DOI: 10.7759/cureus.10741] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Multiple system atrophy (MSA) is a rare, progressive, fatal, neurodegenerative disorder. There are two main types: the parkinsonian type (MSA-P) and cerebellar type (MSA-C). The disease usually presents with genitourinary dysfunction, orthostatic hypotension, and rapid eye movement (REM) sleep behavior disorder. Patients rapidly develop balance, speech, and coordination abnormalities. We present a review of the clinical picture and the actualized treatment modalities of the MSA cerebellar type. For the study methods, a PubMed search was done using the following medical subject headings (MeSH) terms: “multiple system atrophy/therapy". Inclusion criteria included studies in English, full papers, human studies, and publications in the last 30 years. Case reports and series were excluded. A total of 157 papers were extracted after applying the inclusion and exclusion criteria, and 41 papers were included for the discussion of this review. This review underlines the therapeutic strategies as well as the clinical picture of multiple system atrophy, and how MSA-C and MSA-P differ from each other. We discussed this review in four topics: ataxia, autonomic dysfunction (neurogenic orthostatic hypotension and urinary disorders), parkinsonism, and REM sleep disorder. In conclusion, the treatment of MSA-C is mainly symptomatic; there are not many studies on MSA-C. The ataxic component and fewer parkinsonian symptoms are the main difference of MSA-C as opposed to MSA-P.
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Affiliation(s)
- Juan Fernando Ortiz
- Neurology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Sagari Betté
- Neurology, Parkinson's Disease and Movement Disorder Center of Boca Raton, Boca Raton, USA
| | - Willians Tambo
- Neurology, Universidad San Francisco de Quito, Quito, ECU
| | - Feiyang Tao
- Neurology, School of Medicine, University of California, Irvine, Irvine, USA
| | - Jazmin Carolina Cozar
- Medicine, Universidad de las Américas, Quito, ECU.,Family Medicine, Open Door Family Medical Center, Portchester, USA
| | - Stuart Isaacson
- Neurology, Parkinson's Disease and Movement Disorder Center of Boca Raton, Boca Raton, USA
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Liu D, Flory J, Lin A, Offin M, Falcon CJ, Murciano-Goroff YR, Rosen E, Guo R, Basu E, Li BT, Harding JJ, Iyer G, Jhaveri K, Gounder MM, Shukla NN, Roberts SS, Glade-Bender J, Kaplanis L, Schram A, Hyman DM, Drilon A. Characterization of on-target adverse events caused by TRK inhibitor therapy. Ann Oncol 2020; 31:1207-1215. [PMID: 32422171 PMCID: PMC8341080 DOI: 10.1016/j.annonc.2020.05.006] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 05/04/2020] [Accepted: 05/05/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The tropomyosin receptor kinase (TRK) pathway controls appetite, balance, and pain sensitivity. While these functions are reflected in the on-target adverse events (AEs) observed with TRK inhibition, these AEs remain under-recognized, and pain upon drug withdrawal has not previously been reported. As TRK inhibitors are approved by multiple regulatory agencies for TRK or ROS1 fusion-positive cancers, characterizing these AEs and corresponding management strategies is crucial. PATIENTS AND METHODS Patients with advanced or unresectable solid tumors treated with a TRK inhibitor were retrospectively identified in a search of clinical databases. Among these patients, the frequency, severity, duration, and management outcomes of AEs including weight gain, dizziness or ataxia, and withdrawal pain were characterized. RESULTS Ninety-six patients with 15 unique cancer histologies treated with a TRK inhibitor were identified. Weight gain was observed in 53% [95% confidence interval (CI), 43%-62%] of patients and increased with time on TRK inhibition. Pharmacologic intervention, most commonly with glucagon-like peptide 1 analogs or metformin, appeared to result in stabilization or loss of weight. Dizziness, with or without ataxia, was observed in 41% (95% CI, 31%-51%) of patients with a median time to onset of 2 weeks (range, 3 days to 16 months). TRK inhibitor dose reduction was the most effective intervention for dizziness. Pain upon temporary or permanent TRK inhibitor discontinuation was observed in 35% (95% CI, 24%-46%) of patients; this was more common with longer TRK inhibitor use. TRK inhibitor reinitiation was the most effective intervention for withdrawal pain. CONCLUSIONS TRK inhibition-related AEs including weight gain, dizziness, and withdrawal pain occur in a substantial proportion of patients receiving TRK inhibitors. This safety profile is unique relative to other anticancer therapies and warrants careful monitoring. These on-target toxicities are manageable with pharmacologic intervention and dose modification.
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Affiliation(s)
- D Liu
- Department of Pharmacy, Memorial Sloan Kettering Cancer Center, New York, USA
| | - J Flory
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA; Department of Medicine, Weill Cornell Medical College, New York, USA
| | - A Lin
- Department of Medicine, Weill Cornell Medical College, New York, USA; Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - M Offin
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA; Department of Medicine, Weill Cornell Medical College, New York, USA
| | - C J Falcon
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Y R Murciano-Goroff
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
| | - E Rosen
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
| | - R Guo
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
| | - E Basu
- Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - B T Li
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA; Department of Medicine, Weill Cornell Medical College, New York, USA
| | - J J Harding
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA; Department of Medicine, Weill Cornell Medical College, New York, USA
| | - G Iyer
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA; Department of Medicine, Weill Cornell Medical College, New York, USA
| | - K Jhaveri
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA; Department of Medicine, Weill Cornell Medical College, New York, USA
| | - M M Gounder
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA; Department of Medicine, Weill Cornell Medical College, New York, USA
| | - N N Shukla
- Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, USA
| | - S S Roberts
- Department of Medicine, Weill Cornell Medical College, New York, USA; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, USA
| | - J Glade-Bender
- Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, USA
| | - L Kaplanis
- Department of Nursing, Memorial Sloan Kettering Cancer Center, New York, USA
| | - A Schram
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA; Department of Medicine, Weill Cornell Medical College, New York, USA
| | - D M Hyman
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA; Department of Medicine, Weill Cornell Medical College, New York, USA
| | - A Drilon
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA; Department of Medicine, Weill Cornell Medical College, New York, USA.
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Kalra DK, Raina A, Sohal S. Neurogenic Orthostatic Hypotension: State of the Art and Therapeutic Strategies. CLINICAL MEDICINE INSIGHTS-CARDIOLOGY 2020; 14:1179546820953415. [PMID: 32943966 PMCID: PMC7466888 DOI: 10.1177/1179546820953415] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 07/31/2020] [Indexed: 11/22/2022]
Abstract
Neurogenic orthostatic hypotension (nOH) is a subtype of orthostatic hypotension in which patients have impaired regulation of standing blood pressure due to autonomic dysfunction. Several primary and secondary causes of this disease exist. Patients may present with an array of symptoms making diagnosis difficult. This review article addresses the epidemiology, pathophysiology, causes, clinical features, and management of nOH. We highlight various pharmacological and non-pharmacological approaches to treatment, and review the recent guidelines and our approach to nOH.
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Affiliation(s)
- Dinesh K Kalra
- Division of Cardiology, Rush University Medical Center, Chicago, IL, USA
| | - Anvi Raina
- Department of Medicine, Rush University Medical Center, Chicago, IL, USA
| | - Sumit Sohal
- Division of Internal Medicine, AMITA Health Saint Francis Hospital, Evanston, IL, USA
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Alghalayini K. Value of ambulatory blood pressure measurement in diagnosing hypotension in hypertensive diabetic patients with medication-controlled BP. JRSM Cardiovasc Dis 2020; 9:2048004020930883. [PMID: 32595964 PMCID: PMC7298423 DOI: 10.1177/2048004020930883] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 05/02/2020] [Accepted: 05/11/2020] [Indexed: 01/01/2023] Open
Abstract
Background Hypotension is a common clinical finding in diabetic patients on anti-hypertensive medications. In the absence of clearly defined and documented hypotensive episodes, clinicians are faced with the challenge of modifying antihypertensive medication in potentially symptomatic diabetic patients. Objective To determine the value of ambulatory blood pressure monitor (ABPM) in diagnosing hypotensive episodes in hypertensive diabetic patients with medication-controlled blood pressure. Patients and methods The records of all hypertensive diabetic patients with medication-controlled were obtained between 2017 and 2018. Patients' demographic data, comorbid conditions, hypotensive symptoms and echocardiography results were obtained and compared to office-based blood pressure and ABPM. Results Of 926 patients screened in the department of medicine outpatient clinics, 231 patients had diabetes and hypertension and were taking antihypertension medications, so only 86 patients were recruited. Using 24 h ABPM, hypotensive events were documented in 65 (75.6%) patients without correlated hypotensive symptoms in the patient sheet. Patients who had hypotensive episodes recorded by ABPM tended to have these between 5 and 10 a.m. and were significantly older - 60.71 versus 58.76 (P = .022) - and more likely to have lower ejection fractions by echocardiography 46.31 versus 62.85 (EF) (P < .001). Conclusion In treated hypertensive diabetic patients with antihypertensive medication, ABPM may be beneficial in capturing bouts of asymptomatic (silent) hypotension readings that occur in the out-of-hospital setting. Diabetic patients with controlled hypertension based on office reading showed a significant number of asymptomatic hypotensive readings detected with ambulatory BP monitoring that can have a role in following up such patients.
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Affiliation(s)
- Kamal Alghalayini
- Department of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
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Sasaki H, Kawamura N, Dyck PJ, Dyck PJB, Kihara M, Low PA. Spectrum of diabetic neuropathies. Diabetol Int 2020; 11:87-96. [PMID: 32206478 PMCID: PMC7082443 DOI: 10.1007/s13340-019-00424-7] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 12/29/2019] [Indexed: 02/06/2023]
Abstract
The diabetic state results in neuropathy. The main causative mechanism is hyperglycemia, although microvascular involvement, hypertriglyceridemia, as well as genetic and immune mechanisms may be contributory. There is a growing spectrum of types of diabetic neuropathies that differ based on the type of fibers involved (e.g. myelinated, unmyelinated, autonomic, somatic), distribution of nerves involved, and mechanisms of neuropathy. The most common type is distal sensory neuropathy (DSN), which affects the distal ends of large myelinated fibers, more often sensory than motor, and is often asymptomatic. The next-most common is distal small fiber neuropathy (DSFN), which largely affects the unmyelinated fibers and carries the phenotype of burning feet syndrome. Diabetic autonomic neuropathy (DAN) occurs when widespread involvement of autonomic unmyelinated fibers occurs, and patients can be incapacitated with orthostatic hypotension as well as neurogenic bladder and bowel involvement. Radiculoplexus diabetic neuropathy causes proximal weakness and pain, usually in the lower extremity, and has a combination of immune, inflammatory, and vascular mechanisms. The nerve roots and plexus are involved. These patients present with proximal weakness of a subacute onset, often with severe pain and some autonomic failure. Finally, rapid and sustained reduction of blood glucose can result in treatment-induced diabetic neuropathy (TIND), which largely affects the sensory and autonomic fibers. This occurs if HbA1c is rapidly reduced within 3 months, and the likelihood is proportional to the original A1c and the size of the reduction.
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Affiliation(s)
| | | | - Peter J. Dyck
- Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 USA
| | - P. James B. Dyck
- Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 USA
| | | | - Phillip A. Low
- Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 USA
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Kim JB, Kim H, Sung JH, Baek SH, Kim BJ. Heart-Rate-Based Machine-Learning Algorithms for Screening Orthostatic Hypotension. J Clin Neurol 2020; 16:448-454. [PMID: 32657066 PMCID: PMC7354974 DOI: 10.3988/jcn.2020.16.3.448] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 04/05/2020] [Accepted: 04/08/2020] [Indexed: 12/15/2022] Open
Abstract
Background and Purpose Many elderly patients are unable to actively stand up by themselves and have contraindications to performing the head-up tilt test (HUTT). We aimed to develop screening algorithms for diagnosing orthostatic hypotension (OH) before performing the HUTT. Methods This study recruited 663 patients with orthostatic intolerance (78 with and 585 without OH, as confirmed by the HUTT) and compared their clinical characteristics. Univariate and multivariate analyses were performed to investigate potential predictors of an OH diagnosis. Machine-learning algorithms were applied to determine whether the accuracy of OH prediction could be used for screening OH without performing the HUTT. Results Differences between expiration and inspiration (E-I differences), expiration:inspiration ratios (E:I ratios), and Valsalva ratios were smaller in patients with OH than in those without OH. The univariate analysis showed that increased age and baseline systolic blood pressure (BP) as well as decreased E-I difference, E:I ratio, and Valsalva ratio were correlated with OH. In the multivariate analysis, increased baseline systolic BP and decreased Valsalva ratio were found to be independent predictors of OH. Using those variables as input features, the classification accuracies of the support vector machine, k-nearest neighbors, and random forest methods were 84.4%, 84.4%, and 90.6%, respectively. Conclusions We have identified clinical parameters that are strongly associated with OH. Machine-learning analysis using those parameters was highly accurate in differentiating OH from non-OH patients. These parameters could be useful screening factors for OH in patients who are unable to perform the HUTT.
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Affiliation(s)
- Jung Bin Kim
- Department of Neurology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Hayom Kim
- Department of Neurology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Joo Hye Sung
- Department of Neurology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Seol Hee Baek
- Department of Neurology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Byung Jo Kim
- Department of Neurology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.
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Byun JI, Kim DY, Moon J, Shin HR, Sunwoo JS, Lee WJ, Lee HS, Park KI, Lee ST, Jung KH, Jung KY, Kim M, Lee SK, Chu K. Efficacy of atomoxetine versus midodrine for neurogenic orthostatic hypotension. Ann Clin Transl Neurol 2019; 7:112-120. [PMID: 31856425 PMCID: PMC6952305 DOI: 10.1002/acn3.50968] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Revised: 11/21/2019] [Accepted: 11/22/2019] [Indexed: 11/11/2022] Open
Abstract
Objective The efficacy and safety of 1‐month atomoxetine and midodrine therapies were compared. Three‐month atomoxetine and combination therapies were investigated for additional benefits. Methods This prospective open‐label randomized trial included 50 patients with symptomatic neurogenic orthostatic hypotension (nOH). The patients received either atomoxetine 18 mg daily or midodrine 5 mg twice daily and were evaluated 1 and 3 months later. Those who still met the criteria for nOH at 1 month received both midodrine and atomoxetine for an additional 2 months, and if not, they continued their initial medication. The primary outcome was an improvement in orthostatic blood pressure (BP) drop (maximum BP change from supine to 3 min after standing) at 1 month. The secondary endpoints were symptom scores, percentage of patients with nOH at 1 and 3 months. Results Patients with midodrine or atomoxetine treatment showed comparative improvement in the orthostatic BP drop, and overall only 26.2% of the patients had nOH at 1 month, which was similar between the treatment groups. Only atomoxetine resulted in significant symptomatic improvements at 1 month. For those without nOH at 1 month, there was additional symptomatic improvement at 3 months with their initial medication. For those with nOH at 1 month, the combination treatment resulted in no additional improvement. Mild‐to‐moderate adverse events were reported by 11.6% of the patients. Interpretation One‐month atomoxetine treatment was effective and safe in nOH patients. Atomoxetine improved orthostatic BP changes as much as midodrine and was better in terms of ameliorating nOH symptoms.
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Affiliation(s)
- Jung-Ick Byun
- Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovations, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.,Department of Neurology, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea.,Program in Neuroscience, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Do-Yong Kim
- Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovations, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jangsup Moon
- Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovations, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.,Program in Neuroscience, Seoul National University College of Medicine, Seoul, Republic of Korea.,Rare Disease Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hye-Rim Shin
- Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovations, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.,Program in Neuroscience, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jun-Sang Sunwoo
- Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovations, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.,Department of Neurosurgery, Seoul National University Hospital, Seoul, Republic of Korea
| | - Woo-Jin Lee
- Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovations, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.,Program in Neuroscience, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Han-Sang Lee
- Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovations, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.,Program in Neuroscience, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Kyung-Il Park
- Department of Neurology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea
| | - Soon-Tae Lee
- Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovations, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.,Program in Neuroscience, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Keun-Hwa Jung
- Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovations, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.,Program in Neuroscience, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ki-Young Jung
- Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovations, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.,Program in Neuroscience, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Manho Kim
- Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovations, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.,Program in Neuroscience, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sang Kun Lee
- Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovations, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.,Program in Neuroscience, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Kon Chu
- Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovations, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.,Program in Neuroscience, Seoul National University College of Medicine, Seoul, Republic of Korea
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41
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Abstract
Parkinson disease (PD) is associated with a variety of motor and non-motor clinical manifestations, including cardiovascular autonomic dysfunction. Neurogenic orthostatic hypotension (nOH) is a potentially serious manifestation of cardiovascular sympathetic failure that occurs in approximately 30% of patients with PD. Here we review the pathophysiology and effects of the condition as well as treatment considerations for patients with PD and nOH. Screening for nOH using orthostatic symptom questionnaires, orthostatic blood pressure measurements, and specialized autonomic testing is beneficial for the identification of symptomatic and asymptomatic cases because cardiac sympathetic denervation and nOH can occur even at early (premotor) stages of PD. Symptoms of nOH, such as orthostatic lightheadedness, in patients with PD, have been shown to adversely affect patient safety (with increased risk of falls) and quality of life and should prompt treatment with non-pharmacologic and, occasionally, pharmacologic measures. Patients with nOH are also at increased risk of supine hypertension, which requires balancing various management strategies. FUNDING: Lundbeck (Deerfield, IL).
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Affiliation(s)
| | - Phillip A Low
- Department of Neurology, Mayo Clinic, Rochester, MN, USA
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42
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Robinson L, Kimpinski K. Neurogenic orthostatic hypotension impairs information processing speed and attention. Physiol Behav 2019; 211:112682. [PMID: 31526820 DOI: 10.1016/j.physbeh.2019.112682] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 09/11/2019] [Accepted: 09/12/2019] [Indexed: 11/15/2022]
Abstract
Neurogenic orthostatic hypotension (NOH) is characterized by a drop in systolic blood pressure (SBP) ≥20 mmHg or diastolic blood pressure (DBP) ≥10 mmHg within three minutes of upright posture. NOH is common in the elderly population. This group of individuals is at an increased risk for deficits in multiple cognitive domains such as information processing speed (IPS) and attention. The objective of the current study was to investigate the change in IPS and attention during head-up tilt (HUT) in patients with NOH compared to controls. Cognitive function was assessed in the supine and HUT positions using the symbol digit modalities test (SDMT) which assesses IPS and the Stroop Test which measures attention. 40 participants completed the study, 20 controls (age 64.50 ± 9.25) and 20 NOH patients (age 69.55 ± 7.43) with associated conditions of Parkinson's disease (n = 11), multiple systems atrophy (n = 3), early Lewy body dementia (n = 1) and idiopathic NOH (n = 5). NOH patients had no difference in IPS between supine (43.20 ± 15.26) and HUT (42.90 ± 14.33; p = .77). Controls had significantly faster IPS in the HUT position (69.90 ± 12.02) compared to supine (63.55 ± 9.96; p < .001). NOH patients had significantly slower IPS in both the supine and HUT position compared to controls (p < .001). Attention in the HUT position was significantly worse in NOH patients (-14.86 ± 8.96) compared to controls (-8.68 ± 7.13; p = .029). During HUT, NOH patients experienced a significant decrease in mean SBP by -64.11 ± 18.96 from baseline, whereas controls only had a mean decrease of -5.69 ± 7.65. It is evident that NOH patients have impaired IPS and attention compared to controls and likely plays an important role in the morbidity of these individuals.
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Affiliation(s)
| | - Kurt Kimpinski
- School of Kinesiology, Western University, London, ON, Canada; Department of Clinical Neurological Sciences, Rm B7-140, University Hospital, London Health Sciences Centre, 339 Windermere Road, London, ON N6A 5A5, Canada; Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
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43
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Cohen A, Vidal JS, Roca F, Rananja H, Hernandorena I, Coude du Foresto L, Seux ML, Rigaud AS, Hanon O, Duron E. Feasibility and Determinants of Orthostatic Hypotension Self-measurement at Home in an Elderly Community-Dwelling Population. Am J Hypertens 2019; 32:824-832. [PMID: 31045224 DOI: 10.1093/ajh/hpz066] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Revised: 02/25/2019] [Accepted: 04/19/2019] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Orthostatic hypotension (OH) measurement reproducibility is poor. Our objectives were to assess feasibility of self-detection home-measured OH (HOH) and HOH determinants. METHODS Subjects older than 65 years, attending a geriatric outpatient clinic, able to understand the HOH protocol: 3 blood pressure (BP) measures after 5 minutes of seating and BP measures after 1 and 3 minutes of standing, each morning and evening for 3 consecutive days were lent a validated digital automatic sphygmomanometer. Reports containing at least 4 correct measurements were deemed a success. Factors associated with HOH were studied. RESULTS HOH feasibility was 82.8% (241 subjects) with no difference between participants who failed or succeeded. Among the 241 subjects (mean age (SD) = 78.0 (8.3) years old; 62.1% of women), 139 were free of HOH, 70 had 1 HOH episode and 32 had 2 or more HOH episodes. Hypertension, dementia, atrial fibrillation, diabetes, and heart failure were found in 70.0%, 10.4%, 9.4%, 8.8%, and 3.4% of cases, respectively. Subjects were treated with antihypertensive, benzodiazepine, statin medication in 47.3%, 9.3%, 7.4% of cases, respectively, and 42.4% experienced polypharmacy. HOH episodes were associated with dementia (P = 0.01), presence of OH during the geriatric outpatient clinic assessment (P = 0.0002), statin therapy (P = 0.04), and polypharmacy (P = 0.0002). In multivariate analysis, benzodiazepine (OR (95% CI) = 2.59 (1.10-6.08) and statin medication (OR (95% CI) = 1.92 (1.10-3.33)) remained significantly associated with HOH. CONCLUSIONS HOH had a good feasibility and relevant determinants. A study to address the predictive value of HOH will be conducted.
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Affiliation(s)
- Adrien Cohen
- Service de Gériatrie, AP-HP, Hôpital Broca, Paris, France
- EA 4468, Sorbonne Paris Cité, Université Paris Descartes, Paris, France
| | - Jean-Sébastien Vidal
- Service de Gériatrie, AP-HP, Hôpital Broca, Paris, France
- EA 4468, Sorbonne Paris Cité, Université Paris Descartes, Paris, France
| | - Frédéric Roca
- Service de Gériatrie, AP-HP, Hôpital Broca, Paris, France
- EA 4468, Sorbonne Paris Cité, Université Paris Descartes, Paris, France
- Service de médecine interne gériatrique, CHU Rouen, Rouen, France
| | - Hanta Rananja
- Service de Gériatrie, AP-HP, Hôpital Broca, Paris, France
- EA 4468, Sorbonne Paris Cité, Université Paris Descartes, Paris, France
| | - Intza Hernandorena
- Service de Gériatrie, AP-HP, Hôpital Broca, Paris, France
- EA 4468, Sorbonne Paris Cité, Université Paris Descartes, Paris, France
| | - Laurent Coude du Foresto
- Service de Gériatrie, AP-HP, Hôpital Broca, Paris, France
- EA 4468, Sorbonne Paris Cité, Université Paris Descartes, Paris, France
| | - Marie-Laure Seux
- Service de Gériatrie, AP-HP, Hôpital Broca, Paris, France
- EA 4468, Sorbonne Paris Cité, Université Paris Descartes, Paris, France
| | - Anne-Sophie Rigaud
- Service de Gériatrie, AP-HP, Hôpital Broca, Paris, France
- EA 4468, Sorbonne Paris Cité, Université Paris Descartes, Paris, France
| | - Olivier Hanon
- Service de Gériatrie, AP-HP, Hôpital Broca, Paris, France
- EA 4468, Sorbonne Paris Cité, Université Paris Descartes, Paris, France
| | - Emmanuelle Duron
- Service de Gériatrie, AP-HP, Hôpital Broca, Paris, France
- APHP, Hôpital Paul Brousse, Villejuif, Paris, France
- Université Paris-Sud XI, Le Kremlin-Bicêtre, Paris, France
- Centre de recherche en Epidémiologie et Santé des Populations, INSERM UMR-1178, Université Paris-Sud XI, Le Kremlin Bicêtre, Paris, France
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44
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Abstract
In this chapter, we describe the history, presentation, diagnosis and treatment of pure autonomic failure (PAF). The pathology underlying this condition is thought to involve the deposition of alpha synuclein in the autonomic ganglia leading to diminished norepinephrine release and progressive autonomic dysfunction. We focus on various neurophysiological tests that may be used to evaluate the function of the peripheral autonomic nervous system including quantitative sudomotor axon reflex testing, thermoregulatory sweat testing, and others. These may help evaluate and diagnose various disorders of autonomic failure and neurogenic orthostatic hypotension including multiple system atrophy and Parkinson's disease dysautonomia. Management of PAF, including the therapeutic role of recent advances in pharmacologic treatment, is discussed.
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45
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Abstract
PURPOSE OF REVIEW Autonomic dysfunction is common in dementia, particularly in the Lewy body dementias. This review considers the evidence for autonomic dysfunction in dementia, common symptoms and potential management options. RECENT FINDINGS Autonomic dysfunction has been shown in Alzheimer's disease and Lewy body dementias. Common symptoms include orthostatic dizziness, syncope, falls, urinary tract symptoms and constipation. Non-pharmacological management of orthostatic hypotension should include bolus water drinking. Pharmacological management may include the use of midodrine or droxidopa although the latter is not available in Europe. Atomoxetine is a noradrenaline reuptake inhibitor which may be useful if further clinical trials become available. Management of constipation may include the use o f probiotics, osmotic laxatives such as macrogol and chloride type 2 channel activators such as lubiprostone. Management of urinary tract symptoms may include the use of mirabegron. There is a dearth of clinical trials for autonomic dysfunction in dementia and most of the evidence is imputed from trials in Parkinson's disease. However, pragmatic recommendations may be made. There is a need for controlled clinical trials in people with dementia.
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Affiliation(s)
- Louise M Allan
- Institute of Health Research, College of Medicine and Health, University of Exeter, South Cloisters Building, St Luke's Campus, Heavitree Road, Exeter, EX1 2LU, UK.
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46
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Physical and Edema Therapy Management of Amyloidosis in the Acute Care Setting: A Case Report. REHABILITATION ONCOLOGY 2019. [DOI: 10.1097/01.reo.0000000000000129] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
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Pérez-Lloret S, Quarracino C, Otero-Losada M, Rascol O. Droxidopa for the treatment of neurogenic orthostatic hypotension in neurodegenerative diseases. Expert Opin Pharmacother 2019; 20:635-645. [PMID: 30730771 DOI: 10.1080/14656566.2019.1574746] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION L-threo-3,4-dihydroxyphenylserine (droxidopa), a pro-drug metabolized to norepinephrine in nerve endings and other tissues, has been commercially available in Japan since 1989 for treating orthostatic hypotension symptoms in Parkinson's disease (PD) patients with a Hoehn & Yahr stage III rating, as well as patients with Multiple System Atrophy (MSA), familial amyloid polyneuropathy, and hemodialysis. Recently, the FDA has approved its use in symptomatic neurogenic orthostatic hypotension (NOH). Areas covered: The authors review the effects of droxidopa in NOH with a focus on the neurodegenerative diseases PD, MSA, and pure autonomic failure (PAF). Expert opinion: A few small and short placebo-controlled clinical trials in NOH showed significant reductions in the manometric drop in blood pressure (BP) after posture changes or meals. Larger Phase III studies showed conflicting results, with two out of four trials meeting their primary outcome and thus suggesting a positive yet short-lasting effect of the drug on OH Questionnaire composite score, light-headedness/dizziness score, and standing BP during the first two treatment-weeks. Results appear essentially similar in PD, MSA, and PAF. The FDA granted droxidopa approval in the frame of an 'accelerated approval program' provided further studies are conducted to assess its long-term effects on OH symptoms.
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Affiliation(s)
- Santiago Pérez-Lloret
- a Instituto de Investigaciones Cardiológicas , University of Buenos Aires, National Research Council (ININCA-UBA-CONICET) , Buenos Aires , Argentina.,b Department of Physiology , School of Medicine, University of Buenos Aires (UBA) , Buenos Aires , Argentina
| | - Cecilia Quarracino
- a Instituto de Investigaciones Cardiológicas , University of Buenos Aires, National Research Council (ININCA-UBA-CONICET) , Buenos Aires , Argentina
| | - Matilde Otero-Losada
- a Instituto de Investigaciones Cardiológicas , University of Buenos Aires, National Research Council (ININCA-UBA-CONICET) , Buenos Aires , Argentina
| | - Olivier Rascol
- c Services de Pharmacologie Clinique et Neurosciences, Centre d'Investigation Clinique CIC 1436, NS-Park/FCRIN Network, NeuroToul COEN Center , Université de Toulouse UPS, CHU de Toulouse, INSERM , Toulouse , France
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48
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The Orthostatic Discriminant and Severity Scale (ODSS): an assessment of orthostatic intolerance. Clin Auton Res 2019; 30:69-77. [PMID: 30604164 DOI: 10.1007/s10286-018-00586-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 12/21/2018] [Indexed: 10/27/2022]
Abstract
PURPOSE To assess the ability of the Orthostatic Discriminant and Severity Scale (ODSS) to distinguish symptoms of orthostatic intolerance from non-orthostatic symptoms. METHODS Clinical evaluations and questionnaire responses were collected in 73 healthy controls and 132 patients referred to the Autonomic Disorders Clinic from September 1, 2016, through April 30, 2018, for queries regarding autonomic dysfunction. A receiver operating characteristic (ROC) curve analysis was used to interpret sensitivity and specificity and to determine cutoff scores for symptom assessment. Inter-item reliability was assessed using Cronbach's alpha. To calculate positive and negative predictive powers, patient data were collected in a single-blinded fashion where the researcher collecting questionnaire data was blinded to the clinical evaluation and diagnosis. Predictive powers were calculated using a chi-squared cross-tabulation. RESULTS The orthostatic and non-orthostatic symptoms scores produced ROC curves with an area under the curve of 0.89 and 0.79, respectively. The orthostatic scores yielded a positive and negative predictive power value of 73% and 81%, respectively. Combined, the ODSS identified patients with and without orthostatic symptoms with an overall accuracy of 76%. The reliability of the ODSS was significant, with a Cronbach's alpha of 0.88, and all dichotomous items were deemed worthy of retention following an inter-item reliability assessment. CONCLUSIONS The ODSS demonstrated a strong ability to distinguish patients with and without orthostatic intolerance and demonstrated sensitivity and specificity equivalent to that of other standardized measures. Overall, the ODSS produces symptom scores that are both reliable and useful for both research and clinical practice.
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49
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Yadav R, Rukmani M, Pal P, Sathyaprabha T. Clinical management of neurogenic orthostatic hypotension. ANNALS OF MOVEMENT DISORDERS 2019. [DOI: 10.4103/aomd.aomd_24_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
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50
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Min M, Shi T, Sun C, Liang M, Zhang Y, Wu Y, Sun Y. The association between orthostatic hypotension and dementia: A meta-analysis of prospective cohort studies. Int J Geriatr Psychiatry 2018; 33:1541-1547. [PMID: 30247788 DOI: 10.1002/gps.4964] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Accepted: 07/22/2018] [Indexed: 01/23/2023]
Abstract
OBJECTIVES As for the association between orthostatic hypotension (OH) and dementia, results of published studies are inconsistent; therefore, current substantive conclusions have yet been obtained. This meta-analysis was conducted in hopes of producing progress in this topic. METHODS A systematic database search was performed towards electronic databases including Chinese Biomedical Database, PubMed, Web of Science, Wiley Online Library, ScienceDirect, and the Cochrane Library. Five prospective cohort studies were included. Summary hazard ratio (HR) estimates with 95% confidence intervals (CIs) were calculated by random-effects model. Statistical heterogeneity was assessed with the Cochran Q test and I2 statistic. A sensitivity analysis was also conducted in this meta-analysis. RESULTS A 22.4% higher prevalence of dementia in subjects with OH was obtained (adjusted pooled HR was 1.224; 95% CI: 1.106-1.354; P < .001). This meta-analysis also showed significant associations between OH and 2 dementia subtypes: Alzheimer disease (adjusted pooled HR was 1.175; 95% CI: 1.022-1.351; P = .023) and Vascular dementia (adjusted pooled HR was 1.403; 95% CI: 1.042-1.889; P = .026), respectively. CONCLUSIONS Orthostatic hypotension is positively associated with the overall prevalence of dementia, and it may contribute to the prevalence of Alzheimer disease and Vascular dementia as well.
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Affiliation(s)
- Min Min
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Tingting Shi
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Chenyu Sun
- The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Mingming Liang
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Yun Zhang
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Yile Wu
- The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Yehuan Sun
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.,Centre for Evidence-Based Practice, Anhui Medical University, Hefei, Anhui, China
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