Acetylcholinesterase inhibition in patients with orthostatic intolerance.

The efficacy of current therapeutic measures in orthostatic intolerance (OI) varies among patients and is oftentimes unsatisfactory. New approaches to alleviate symptoms of OI are therefore clearly needed. Recent reports have demonstrated that acetylcholinesterase inhibition is effective in the treatment of orthostatic hypotension with the presumed mechanism of enhancing sympathetic ganglionic transmission. Based on the hypothesis that acetylcholinesterase inhibition, by improving the safety factor of cholinergic transmission, will result in enhanced vascular adrenergic tone and a vagal shift in cardiac sympathovagal balance, we evaluated the role of acetylcholinesterase inhibition in the treatment of patients with OI. We monitored heart rate (HR), blood pressure, and indexes for cardiac output, end-diastolic volume, and systemic resistance continuously in 18 patients with OI during supine rest and during 5 minutes of 70 degrees head-up tilt before and 1 hour after oral administration of 60 mg pyridostigmine. Plasma catecholamines and baroreflex sensitivity were determined for the supine and upright position before and after medication. Patients scored orthostatic symptoms for both tilt studies. The excessive HR response to orthostatic stress was significantly blunted after pyridostigmine administration. HR was significantly lower in the supine and more so in the upright position. Baroreflex sensitivity in the upright position was significantly higher after pyridostigmine. Norepinephrine was increased in both supine and upright position. These changes were associated with significant improvement of orthostatic symptoms. We conclude that pyridostigmine improves orthostatic tolerance in patients with OI. Our findings support the suggested mechanisms of enhanced sympathetic ganglionic neurotransmission and a vagal shift in cardiac sympathovagal balance. Acetylcholinesterase inhibition could be a new useful concept in the treatment of OI.     

Clinical improvement in patients with orthostatic intolerance after treatment with bisoprolol and fludrocortisone

Orthostatic intolerance is the development of disabling symptoms upon assuming an upright posture that are relieved partially by resuming the supine position. Postural tachycardia syndrome (POTS) is an orthostatic intolerance syndrome characterized by palpitations because of excessive orthostatic sinus tachycardia, lightheadedness, tremor, and near-syncope. Patients usually undergo extensive medical, cardiac, endocrine, neurologic, and psychiatric evaluation, which usually fails to identify a specific abnormality. The authors investigated the autonomic and hemodynamic profile of patients with POTS and the effectiveness of bisoprolol and fludrocortisone. The authors evaluated 11 female patients with POTS before and after medical treatment with a cardioselective bisoprolol -blocker or fludrocortisone, or both, and 11 age-matched control patients. Variability of heart rate and systolic blood pressure was assessed by fast Fourier transform, and spontaneous baroreceptor gain was assessed by use of the temporal sequences slope and index. Modelflow was used to quantify hemodynamics. Symptoms in all patients improved greatly after medication. The autonomic and hemodynamic impairment observed in patients with POTS, particularly after orthostatic stress, is treated effectively with bisoprolol or fludrocortisone or both. These results need further confirmation in a controlled double-blind study. Proper medical treatment improves dramatically the clinical and autonomic-hemodynamic disturbances observed in patients with POTS. The data support the hypothesis that POTS is the result of a hyperadrenergic activation or hypovolemia during orthostasis.     

全麻下腹部手术患者的围术期睡眠质量对术后恢复的影响

目的 探讨全麻患者围手术期睡眠质量对腹部手术患者术后胃肠功能恢复、疼痛程度及麻醉药物用量的影响.方法 纳入2018年2月～2019年10月在XX医院胃肠外科行全麻手术的胃肠道疾病患者100例,术前1天采用匹兹堡睡眠质量指数量表对患者近1月睡眠状况进行评估,分为睡眠障碍组和对照组,比较两组患者围手术期麻醉药品丙泊酚、瑞芬...     

No increased herniation of the cerebellar tonsils in a group of patients with orthostatic intolerance

Orthostatic intolerance, seen predominantly in young women, is characterized by symptoms of lightheadedness, fatigue and palpitations in the upright posture. With standing, plasma norepinephrine levels rise dramatically and heart rate often increases by more than 30 beats per minute, although blood pressure does not usually fall. A theory recently popularized in the media suggests that some cases of orthostatic intolerance are related to hindbrain compression, with or without a Chiari I malformation. As a preliminary investigation of this hypothesis, head or cervical spine MRI scans from 23 females with orthostatic intolerance were reviewed. The cerebellar tonsils averaged 0.3 ± 1.9 mm below the foramen magnum. These results were compared to measurements from a control group averaging 0.4 ± 2.6 mm above the foramen magnum (P > 0.05). Tonsillar depression of at least 3 mm occurred in 13 % of both the patient group and the control group. Tonsillar herniation was not found to influence supine or upright blood pressure, heart rate or plasma norepinephrine levels in the patients. We conclude that herniation of the cerebellar tonsils is not a common cause of orthostatic intolerance. However, the single measurement of tonsillar depression might underestimate the number of patients with hindbrain compression. Received: 13 March 2002, Accepted: 30 May 2002 Correspondence to David Robertson, M. D.     

2型糖尿病合并直立不耐受症状的发生率及相关因素分析

目的 探讨2型糖尿病(T2 DM)合并直立不耐受(OI)症状的发生率及相关因素.方法 纳入2020年9月至2021年10月在海南医学院第二附属医院内分泌科住院的糖尿病(DM)患者,收集一般临床资料.完善卧立位经颅多普勒(TCD)试验,记录患者卧位及立位1 min、3 min、5 min、10 min血压、心率及脑血流动...     

利培酮所致不良反应207例综合分析

目的:综合分析利培酮所致不良反应的临床特征.方法:对1997至2005年国内文献利培酮所致不良反应的病例报道96篇、207例患者进行汇总分析.结果:利培酮不良反应的发生多与用药剂量、加药剂量速度及患者的个体差异有关.结论:利培酮用药剂量不宜过大,加药速度不宜过快,用药剂量应注意遵循个体化原则.     

Functional disability in adolescents with orthostatic intolerance and chronic pain

A retrospective review identified 99 adolescents (79% female) referred to a tertiary care center to evaluate the relationship between symptoms of orthostatic intolerance and chronic pain. Regression analysis indicated that functional disability was strongly associated with pain intensity (P < .001) and depression (P = .024). The association between functional disability and number of symptoms of orthostatic intolerance trended toward significance (P = .057). Meeting a threshold heart rate increment of 30 beats per minute on head-up tilt was not associated with functional disability (P = .188). Separate regression analysis of female patients showed similar results to the full sample but with a stronger relationship between depression and functional disability and a weaker relationship between heart increment and functional disability. In this sample of adolescents with symptoms of orthostatic intolerance and chronic pain, pain intensity and depression were associated with functional status, but postural tachycardia was not. Further research is needed to clarify potential gender differences.     

Topiramate and psychiatric adverse events in patients with epilepsy

PURPOSE: The aim of this study was to determine the prevalence of psychiatric adverse events (PAEs) in patients with epilepsy treated with topiramate (TPM). Classification, relation to TPM dosing, and outcome were evaluated to identify a patient profile at risk of developing PAEs. METHODS: We evaluated the data of the first consecutive and prospectively collected patients in therapy with TPM. RESULTS: Follow-up information was available for 431 patients. PAEs occurred in 103 (23.9%) patients; M/F ratio, 55:48; mean age (+/-SD), 36.5 +/- 11.2. In 46 (10.7%) patients, an affective disorder developed; in 16 (3.7%), a psychotic disorder; in 24 (5.6%), aggressive behavior with or without irritability; in 17 (3.9%), other behavior abnormalities such as agitated behavior, anger/hostility behavior, or anxiety. High starting dose and rapid titration schedule were relevant for the development of PAEs. Family psychiatric history and family history of epilepsy, personal history of febrile convulsions, psychiatric history, and presence of tonic-atonic seizures were found to be significant risk factors. Low seizure frequency before starting TPM and TPM/lamotrigine coadministration had a protective effect for PAEs. CONCLUSIONS: We found that PAEs associated with TPM were related to the titration schedule of the drug and that a unique patient profile is suggested by the clinical history.     

Assessment of capillary fluid shifts during orthostatic stress in normal subjects and subjects with orthostatic intolerance

Orthostatic stress causes, in addition to venous pooling, a loss of plasma fluid from capillaries to the dependent tissues. The rate of this loss may be one of the factors determining orthostatic tolerance. In this study we assessed the use of a multichannel impedance plethysmograph for determining changes in volume in the calf, thigh, and abdominal segments, in asymptomatic volunteers and in patients shown to have poor tolerance to orthostatic stress. Impedance plethysmography showed, for leg segments, that following head-up tilt there was an initial rapid change in volume followed after 2 to 4 minutes by an almost linear change. Results from the abdominal segment were more variable. The rate of change of leg (thigh+calf) volume was significantly correlated with the estimated loss of plasma volume derived from the changes in the concentration of plasma protein, using evans Blue dye as the marker. Comparison of results of leg filtration rates between patients and volunteers indicated that some of the patients had abnormally high filtration rates and suggests that impedance plethysmography may have a role in assessing the possible reasons for orthostatic intolerance.     

Orthostatic heart rate does not predict symptomatic burden in pediatric patients with chronic orthostatic intolerance

Clinical Autonomic Research - Postural orthostatic tachycardia syndrome (POTS) in adults is defined as symptoms of chronic orthostatic intolerance (COI) and autonomic dysfunction (AD) with heart...     

The role of otolith reflexes in orthostatic intolerance

Clinical Autonomic Research -     

Non-interventional surveillance study of adverse events in patients with epilepsy

Cruise KE, Bucks RS, Loftus AM, Newton RU, Pegoraro R, Thomas MG. Exercise and Parkinson’s: benefits for cognition and quality of life.
Acta Neurol Scand: 2011: 123: 13–19.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objectives – The benefits of physical exercise for psychological aspects of quality of life (QoL) are well established in normally ageing adults, yet potential benefits for people with Parkinson’s disease (PD) have received limited attention. This study evaluated the benefits of exercise for cognitive functioning, mood and disease‐specific QoL for people with PD. Methods – Twenty‐eight individuals with PD were allocated to an exercise intervention program (EIP, n = 15) or control group (n = 13). The EIP group undertook a programme of progressive anabolic and aerobic exercise twice weekly for 12 weeks. The control group maintained their usual lifestyle. Results – Exercise was shown to have selective benefits for cognitive functioning by improving frontal lobe based executive function. No significant effects were demonstrated for mood or disease‐specific QoL. Conclusions – These results are consistent with previous research demonstrating selective benefits of exercise for executive function among normal ageing adults and PD.     

Cortisol response to surgery and postoperative confusion in depressed patients under general anesthesia with fentanyl

The purpose of this study was to investigate the relationship between postoperative confusion and plasma cortisol response to surgery in depressed patients. We studied 80 depressed patients and 40 control patients who had undergone orthopedic surgery and perioperatively measured plasma cortisol and adrenocorticotropin levels. Postoperative confusion in the first 3 postoperative days occurred in 5 (13%) depressed patients given fentanyl during anesthesia, 13 (33%) patients without fentanyl and 1 (3%) control patients. Plasma cortisol concentration (19.7 +/- 6.9 and 19.2 +/- 8.0 microg dl(-1)) 15 min after skin incision and 60 min after the end of surgery in depressed patients with fentanyl was significantly lower than that (24.2 +/- 7.2 and 23.5 +/- 8.1 microg dl(-1)) of depressed patients without fentanyl. Plasma cortisol levels during and after surgery in depressed patients with postoperative confusion were higher than those of depressed patients without postoperative confusion. We conclude that the occurrence of postoperative confusion in depressed patients is associated with an increase in plasma cortisol levels during and after surgery. The incidence of postoperative confusion in depressed patients with fentanyl was significantly lower than that of depressed patients without fentanyl.     

Fludrocortisone improves nausea in children with orthostatic intolerance (OI)

Introduction/Results  

In 17 patients, chronic idiopathic nausea was associated with orthostatic intolerance (OI) by abnormal tilt table tests (88%) or gastric dysrhythmias (71%). After fludrocortisone treatment, there was >26% nausea improvement in 71%, 1–25% in 6%, and no improvement in 24%. In six subjects, EGGs repeated after >50% nausea improvement all remained to be abnormal, suggesting nausea is independent of gastric dysrhythmias.     

Cardiovascular autonomic dysfunction in multiple sclerosis: correlation with orthostatic intolerance

Autonomic dysfunction is frequently observed in patients with multiple sclerosis (MS), but clinical studies disagree on the frequency and type of abnormalities in autonomic function tests. Orthostatic dizziness (OD) has been reported in up to 49% of patients, but the pathophysiological mechanisms are poorly understood. This study investigated cardiovascular reflex tests and their association with OD in patients with MS in order to examine the hypothesis that the sympathetic nervous system is specifically involved in these patients. Forty patients with clinically active relapsing-remitting (n = 27) and secondary progressive MS (n = 13), aged 35.0 ± 8.5 years, were studied by parasympathetic (heart rate responses to the Valsalva maneuver, deep breathing, and active change in posture) and sympathetic function tests (blood pressure responses to active change in posture and sustained handgrip), and by spectral analysis of heart rate variability during rest and during standing. Results were compared to those obtained in 24 healthy volunteers, aged 29.4 ± 7.2 years. A standardized questionnaire was used to evaluate symptoms of orthostatic intolerance. Abnormal responses on at least one cardiovascular reflex test were observed in 40% of MS patients, compared to 17% of the control group, with a statistically significant involvement of the sympathetic vasomotor system. Orthostatic intolerance was reported in 50% of patients (controls: 14%, P < 0.006). Subgroup comparison of patients with and without OD suggests that orthostatic intolerance results from impaired sympathetic vasoconstriction. These results provide further evidence that the sympathetic nervous system is involved in patients with MS. Received: 18 September 1998 Received in revised form: 28 December 1998 Accepted: 3 January 1999     

Cerebrovascular and cardiovascular responses associated with orthostatic intolerance and tachycardia

Idiopathic orthostatic intolerance syndrome is characterized by postural symptoms of cerebral hypoperfusion without arterial hypotension. Abnormal baroreceptor responses with deranged cerebral autoregulation leading to cerebral vasoconstriction have been proposed as a causative mechanism. The authors report the cerebrovascular and cardiovascular responses in a patient who recovered from orthostatic intolerance and tachycardia. Changes in the orthostatic responses of mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and transcranial Doppler middle cerebral artery (MCA) mean blood flow velocity (V_mean) were assessed at admission and again 6 months after recovery. Normal cardiovascular responses to forced breathing and to standing indicated intact overall baroreflex integrity with normal baroreflex sensitivity (10.2 msec·mm Hg⁻¹). After the patient stood for 8 minutes, presyncopal symptoms developed, with unchanged MAP but increased HR (+41 beats/min) and reduced stroke volume (SV) (−69%), CO (−50%), and MCA V_mean (−46%; 57 to 31 cm·s⁻¹). After a reconditioning program and recovery, the patient was reexamined. The supine MCA V_mean was larger (79 cm·s⁻¹), as were MAP (76 versus 70 mm Hg) and CO (+15%). The orthostatic HR increase was smaller (+5 beats/min), as was the reduction in SV (−44%) and CO (−30%), with an increase in MAP to 93 mm Hg. The orthostatic reduction in MCA V_mean was smaller (−13 versus −26 cm·s⁻¹) and standing cerebrovascular resistance decreased (1.41 versus 2.39 mm Hg·cm·s⁻¹). In this patient who had intact baroreflex control and no postural decrease in blood pressure, the reduction in MCA V_mean, concomitant with a large decrease in CO, seemed reversible. The result suggests that a symptomatic reduction in cerebrovascular conductance during standing is to be interpreted as being an adaptive response to a critically limited systemic blood flow, rather than to derangement of cerebral autoregulation.     

右美托咪定滴鼻对颅内动脉瘤介入治疗全麻拔管期血流动力学的影响

目的 观察右美托咪定滴鼻对颅内动脉瘤介入治疗全麻拔管期血流动力学的影响。方法 选择择期行介入治疗的颅内动脉瘤80例，根据滴鼻药物分为4组（n=20），即对照组（C组）和低、中、高剂量右美托咪定组（D1组、D2组、D3组）。手术结束前30 min，D1、D2、D3组用右美托咪定0.6、1.0、1.4 μg/kg滴鼻，C组用生理盐水滴鼻。记录入室时（T0）、滴鼻前即刻（T1）、手术结束时（T2）、患者苏醒时（T3）、拔管时（T4）、拔管后1 min（T5）、5 min（T6）心率（HR）、平均动脉压（MAP）、收缩压与心率的乘积（RPP）；记录术后恢复指标（包括苏醒时间、拔管时间、拔管质量评分、Ramsay镇静评分）。结果 与C组比较，D1组T3~T5、D2和D3组T2~T6 MAP、RPP、HR均明显降低（P<0.05）；D2组和D3组拔管质量评分均明显降低（P<0.05）、Ramsay评分均明显增高（P<0.05），D3组苏醒时间及拔管时间均明显延长（P<0.05）。与D1组比较，D2和D3组T3~T6 MAP、RPP、HR均明显降低（P<0.05），D3组拔管质量评分明显降低（P<0.05）、RamaSay评分明显增高（P<0.05），苏醒时间及拔管时间均明显延长（P<0.05）。与D2组比较，D3组苏醒时间及拔管时间均明显延长（P<0.05）。D2和D3组HR、MAP、RPP、拔管质量评分、Ramsay镇静评分均无统计学差异（P>0.05）。结论 手术结束前30 min给予右美托咪定1.0 μg/kg滴鼻全麻拔管期血流动力学平稳，同时不影响术后恢复。