Faintly tired: a systematic review of fatigue in patients with orthostatic syncope

Background

Orthostatic syncope (transient loss of conscious when standing—fainting) is common and negatively impacts quality of life. Many patients with syncope report experiencing fatigue, sometimes with “brain fog”, which may further impact their quality of life, but the incidence and severity of fatigue in patients with syncope remain unclear. In this systematic review, we report evidence on the associations between fatigue and conditions of orthostatic syncope.

Methods

We performed a comprehensive literature search of four academic databases to identify articles that evaluated the association between orthostatic syncope [postural orthostatic tachycardia syndrome (POTS), vasovagal syncope (VVS), orthostatic hypotension (OH)] and fatigue. Studies were independently screened using a multi-stage approach by two researchers to maintain consistency and limit bias.

Results

Our initial search identified 2797 articles, of which 13 met our inclusion criteria (POTS n?=?10; VVS n?=?1; OH n?=?1; VVS and POTS n?=?1). Fatigue scores were significantly higher in patients with orthostatic syncope than healthy controls, and were particularly severe in those with POTS. Fatigue associated with orthostatic syncope disorders spanned multiple domains, with each dimension contributing equally to increased fatigue. “Brain fog” was an important symptom of POTS, negatively affecting productivity and cognition. Finally, fatigue was negatively associated with mental health in patients with POTS.

Conclusion

In conditions of orthostatic syncope, fatigue is prevalent and debilitating, especially in patients with POTS. The consideration of fatigue in patients with orthostatic disorders is essential to improve diagnosis and management of symptoms, thus improving quality of life for affected individuals.

     

Head-up sleeping improves orthostatic tolerance in patients with syncope

Objectives  This study was designed to examine the effect of head-up sleeping as a treatment for vasovagal syncope in otherwise healthy patients. Treatment for syncope is difficult. Pharmacological treatments have potential side effects and, although other non-pharmacological treatments such as salt and fluid loading often help, in some cases they may be ineffective or unsuitable. Head-up sleeping may provide an alternative treatment. Methods  Twelve patients had a diagnosis of vasovagal syncope based both on the history and on early pre-syncope during a test of head-up tilting and graded lower body suction. They then underwent a period of 3–4 months of sleeping with the head-end of their bed raised by 10°, after which orthostatic tolerance (time to pre-syncope during tilt test) was reassessed. Results  Eleven patients (92%) showed a significant improvement in orthostatic tolerance (time to pre-syncope increased by 2 minutes or more). Plasma volume was assessed in eight patients and was found to show a significant increase (P < 0.05, Wilcoxon signed-rank test). There was no significant change in either resting or tilted heart rate or blood pressure after head-up sleeping. Interpretation  Head-up sleeping is a simple, non-pharmacological treatment which is effective in the majority of patients. However, it may not be tolerated by patients or bed-partners long term and whether the effects continue after cessation of treatment remains to be determined.     

The effects of caffeine in adults with neurogenic orthostatic hypotension: a systematic review

Clinical Autonomic Research - To systematically review the evidence base for the effectiveness and safety of caffeine for the treatment of neurogenic orthostatic hypotension in adults. Eight...     

Cardiac pacing does not improve orthostatic tolerance in patients with vasovagal syncope

This study was undertaken to assess the value of dual chamber pacing in the treatment of vasovagal syncope. In a preliminary study, on two patients the time to presyncope during head-up tilt before and after implanting pacemakers was determined. Both patients fainted with similar decreases in blood pressure at almost exactly the same time after tilting. In the main study, nine patients with pacemakers implanted as treatment for syncope were studied, in random order, with pacemakers on and either off or turned to minimum rate. The pacemakers prevented bradycardia but had no effect on the time to syncope in a progressive test of head-up tilt followed by the addition of graded lower body suction. It is concluded that cardiac pacing does not prevent or even delay the onset of postural syncope and infer that bradycardia is an unimportant component of vasovagal attacks.     

Biological correlates of post-stroke fatigue: a systematic review

Fatigue is a common and disabling consequence of stroke. Its mechanisms are unknown. Neuroanatomical abnormalities (e.g. white matter lesions, brain atrophy), neuroendocrine dysregulation, neurotransmitter changes and inflammation are associated with fatigue in conditions other than stroke. This review sought to identify published studies describing associations between post-stroke fatigue and these biological factors. We searched Medline, EMBASE, CINAHL, PsycINFO and AMED on October 15 and PubMed on 28 December 2010 and included studies in English that recruited at least 10 patients (>18 years old) with stroke, assessed fatigue and reported its relationship with neuroanatomical abnormalities, hypothalamo-pituitary-adrenal axis dysregulation, neurotransmitter changes or inflammation. Of 4916 citations from the searches, 17 studies met our inclusion criteria. There was no association between white matter lesions, brain atrophy or pathological type of stroke and fatigue (seven studies, n = 4746). The data on relationship between lesion location and fatigue were inconclusive: four (n = 675) of 13 studies (n = 1613) showed associations between fatigue and infratentorial lesion location (brainstem in particular) or basal ganglia stroke. One study reported C-reactive protein levels and found an association with fatigue. No studies reported hypothalamo-pituitary-adrenal axis dysregulation or neurotransmitter changes and fatigue. We could not perform meta-analysis because the studies used different methods of fatigue assessment, examined different populations and had different designs. The biological mechanisms of post-stroke fatigue are uncertain. Further studies are required to determine the relationship between post-stroke fatigue and biological factors.     

Increased hydration alone does not improve orthostatic tolerance in patients with neurocardiogenic syncope

In patients with neurocardiogenic syncope, the beneficial effects of increased daily fluid intake, without an accompanying high dose of salt, are unknown. Our aim was to (1) determine whether plasma volume was low in patients with recurrent neurocardiogenic syncope, and (2) determine how recommendation about increased daily fluid intake, without an accompanying high dose of sodium, effects plasma volume and if this potential therapy improves orthostatic tolerance. Eighty-six patients with neurocardiogenic syncope were recruited in a prospective randomized open study. After an initial head-up tilt test, patients were randomly assigned to either the hydration supplementation group (1500 ml of water + 1500 mg of NaCl/day) or the no treatment (control) group. After ten days a second head-up tilt test was performed. Plasma volume, osmolality, and total body water were measured at baseline, and heart rate, arterial blood pressure, and cardiac transthoracic impedance were monitored during tilting. Hydration treatment did not affect the number of positive tilt tests (52% initial day, 54% after treatment, NS). In both groups, the overall number of positive tilt tests decreased between the initial and final head-up tilt test. There was no association between low plasma volume and positive tilt test. Patients with the lowest plasma volume were equally distributed in both positive and negative tilt response groups. An increased daily intake of fluid, without an accompanying high dose of salt, had no measurable beneficial effect on tolerance to head-up tilting in patients with neurocardiogenic syncope. Moreover in this patient group there was no association between a low plasma volume and a reduced tolerance to orthostatic stress.     

Delayed orthostatic hypotension and vasovagal syncope: a diagnostic dilemma

Clinical Autonomic Research -     

Cerebral autoregulation during orthostatic stress in healthy controls and in patients with posturally related syncope

Abstract. Posturally related syncope (PRS) is a common and distressing problem, which frequently occurs in people with no apparent clinical disorder and is ultimately caused by a reduction in blood supply to the brain. The aim of this study was to compare cerebrovascular responses to orthostatic stress in otherwise healthy patients suffering from PRS, and who were shown to have a poor orthostatic tolerance (n=28), with those in healthy control subjects with good orthostatic tolerance (n=11). Responses of heart rate, arterial blood pressure, end tidal carbon dioxide and middle cerebral artery (MCA) blood flow velocity were determined during a progressive orthostatic stress test of combined head-up tilting and lower body suction, which was continued until presyncope. We assessed the efficiency of autoregulation of cerebral blood flow from the relationship between values of MCA velocity and pressure obtained over the expected range for autoregulation (> 55mmHg). All patients with PRS had a significant correlation between MCA velocity and pressure, but this was seen in only two of the controls. Furthermore, the values of the correlation coefficients were significantly higher in patients than controls, (p<0.001). We interpret these data as indicating that autoregulation in patients with PRS is less effective than in controls and suggest that this provides evidence for a link between abnormalities of regulation of the cerebral circulation and predisposition to syncope.     

Arrhythmic syncope in neurogenic orthostatic hypotension: two case reports

Patients with autonomic failure experience orthostatic hypotension (OH) often leading to syncope. Arrhythmias may cause severe syncope, characterized by an increased risk of mortality. We report two cases of patients with primary autonomic neuropathy suffering from both severe OH and arrhythmic syncope.     

Forearm vascular responses during orthostatic stress in control subjects and patients with posturally related syncope

The aim of this study was to compare the changes in forearm vascular resistance that occurred during orthostatic stress in asymptomatic volunteer subjects with those in patients with posturally related syncope. The authors hoped firstly that it would indicate the importance of vasoconstriction in the maintenance of blood pressure, and secondly that it might have diagnostic value if there were differences between symptomatic patients and asymptomatic volunteers. Twelve volunteers and 67 patients with unexplained syncope were classified as early or late fainters, based on their endurance of a test of combined head-up tilting and lower-body suction. Responses of vascular resistance were assessed from the ratio of arterial blood pressure (Finapres) to brachial artery blood velocity (Doppler). Changes in vascular resistance were greater in volunteers at all stages of the procedure than in patients. There was, however, no significant difference between the responses of early and late-fainting volunteers. These results demonstrate the importance of vasoconstriction in the resistance to posturally related syncope, and they indicate that assessments of responses of vascular resistance may improve the accuracy of the diagnosis.     

Electrocardiographic changes in patients with acute stroke: a systematic review

Repolarization and ischemic-like electrocardiographic (ECG) changes observed during acute phase of stroke may cause diagnostic and management dilemmas for the clinician. In this systematic review, we have compiled all information available in the literature on the prevalence of these ECG changes and QT prolongation during the acute phase of stroke and their coexistence with other abnormal cardiac findings. Abnormalities, such as ischemic-like ECG changes and/or QT prolongation, were found in 76% (95% CI 73-90) of patients with subarachnoid hemorrhage, irrespective of whether they had preexisting heart disease or not. Such ECG changes were present in more than 90% of unselected patients with ischemic stroke and intracerebral hemorrhage, but the prevalence was much lower after exclusion of patients with preexisting heart disease. Compared with other abnormal cardiac findings (cardiac wall motion abnormality detected by echocardiography, elevated levels of biochemical markers of myocardial injury, autopsy findings, thallium scintigraphy), these ECG changes were characterized by a high sensitivity but a very low specificity. Thus, in patients with subarachnoid hemorrhage, repolarization and ischemic-like ECG changes are mainly direct consequences of the cerebral condition and their absence essentially rules out cardiac abnormalities. In patients with ischemic stroke and intracerebral hemorrhage, these ECG abnormalities (and QT prolongation) most often represent preexisting coronary artery disease. The specificity of ECG changes to diagnose acute myocardial infarction is low in the acute phase of stroke.     

精神分裂症神经系统软体征的系统综述

目的收集国内外2000年-2014年公开发表的关于精神分裂症神经系统软体征(neurological soft signs,NSS)的文献,综述精神分裂症NSS主要研究领域的最新研究成果,为今后研究精神分裂症NSS提供新的视角和相关理论依据。方法计算机检索Pub Med、Embase、中国知网以及万方数据库,检索精神分裂症神经系统软体征的相关文献。由2位评价员按纳入与排除标准筛选文献,评价纳入研究质量并提取原始资料后,综述精神分裂症神经系统软体征的主要研究成果。结果共检索到相关文献407篇,最终纳入25篇。结果显示精神分裂症NSS与精神分裂症阴性症状以及患者认知功能存在一定的相关性,NSS也渐渐显示出潜在的脑区皮层相关性,同时被认为是潜在的精神分裂症内表型之一。结论神经系统软体征对精神分裂症病理机制的确定具有一定的理论意义,同时对精神分裂症临床工作的完善具有指导作用;建议今后的研究对协变量做出更好的控制,拓展被试样本的年龄跨度,增加纵向研究和遗传学证据。     

Pathogenesis and management of delayed orthostatic hypotention in patients with chronic fatigue syndrome

The relationship between orthostatic hypotension and chronic fatigue syndrome (CFS) has been reported previously. To study the parthogenesis and management of delayed orthostatic hypotension in patients with CFS, a case comparison study with follow-up of 8 weeks has been designed. A group of 78 patients with CFS (mean age 40 years; 49% men and 51% women), who fulfilled the Centre for Disease Control and Prevention criteria were studied. There were 38 healthy controls (mean age 43 years; 47% men and 53% women). At entry to the study each subject underwent an upright tilt-table test, and clinical and laboratory evaluation. Patients with orthostatic hypotension were offered therapy with sodium chloride (1200 mg) in a sustainedrelease formulation for 8 weeks, prior to resubmission to the tilt-table testing, and clinical and laboratory evaluation. An abnormal response to upright tilt was observed in 22 of 78 patients with CFS. After sodium chloride therapy for 8 weeks, tilt-table testing was repeated on the 22 patients with an abnormal response at baseline. Of these 22 patients, 10 redeveloped orthostatic hypotension, while 11 did not show an abnormal response to the test and reported an improvement of CFS symptoms. However, those CFS patients who again developed an abnormal response to tilt-test had a significantly reduced plasma renin activity (0.79 pmol/ml per h) compared both with healthy controls (1.29 pmol/ml per h) and with those 11 chronic fatigue patients (1.0 pmol/ml per h) who improved after sodium chloride therapy (p=0.04). In conclusion, in our study CFS patients who did not respond to sodium chloride therapy were found to have low plasma renin activity. In these patients an abnormal renin-angiotensin-aldosterone system could explain the pathogenesis of orthostatic hypotension and the abnormal response to treatment.     

Initial orthostatic hypotension as a cause of recurrent syncope: A case report

A 60-year-old male patient with recurrent unexplained syncope on standing was studied. During continuous, noninvasive blood pressure (BP) recording with a Finapres device, an abnormally large and symptomatic initial decrease in systemic BP was documented. After 2 minutes of standing, BP had recovered. The transient decrease in BP was attributed to the use of a combination of antidepressants known to interfere with sympathetic function. This case shows the importance of continuous, noninvasive BP measurement on standing: routine intermittent BP recording would have missed the abnormality. In patients using medications such as antidepressants, initial transient hypotension should be considered as the cause of falls and syncope.     

Physical activity in patients with deep venous thrombosis: a systematic review

Objectives

We performed a systematic review to assess the benefits or risks of physical activity in patients with an acute or previous DVT of the leg.

Data sources

PubMed, EMBASE and Science Citation Index were searched without language restrictions up to July 2007. Bibliographies of retrieved articles and personal files were also searched.

Review methods

Randomized trials and prospective cohort studies that included patients with acute or previous DVT, described an exercise intervention or exercise exposure, and described any related clinical outcome were selected. Data were independently extracted by 2 investigators.

Results

Seven randomized trials and two prospective observational studies were included. Early exercise, compared with bed rest, was associated with a similar short-term risk of pulmonary embolism in patients with acute DVT and led to more rapid resolution of limb pain. In patients with acute DVT, a 6 month daily walking program led to similar degrees of vein recanalization and improvement in quality of life as controls. In patients with previous DVT, 30 min of vigorous treadmill exercise did not worsen venous symptoms and improved calf muscle flexibility; a 6 month exercise training program improved calf muscle strength and pump function; and high levels of physical activity at one month tended to be associated with reduced severity of postthrombotic symptoms during the subsequent 3 months.

Conclusions

Early walking exercise is safe in patients with acute DVT and may help to reduce acute symptoms. Exercise training does not increase leg symptoms acutely in patients with a previous DVT and may help to prevent or improve the postthrombotic syndrome.     

Screening tests for aphasia in patients with stroke: a systematic review

Aphasia has a large impact on the quality of life and adds significantly to the costs of stroke care. Early recognition of aphasia in stroke patients is important for prognostication and well-timed treatment planning. We aimed to identify available screening tests for differentiating between aphasic and non-aphasic stroke patients, and to evaluate test accuracy, reliability, and feasibility. We searched PubMed, EMbase, Web of Science, and PsycINFO for published studies on screening tests aimed at assessing aphasia in stroke patients. The reference lists of the selected articles were scanned, and several experts were contacted to detect additional references. Of each screening test, we estimated the sensitivity, specificity, likelihood ratio of a positive test, likelihood ratio of a negative test, and diagnostic odds ratio (DOR), and rated the degree of bias of the validation method. We included ten studies evaluating eight screening tests. There was a large variation across studies regarding sample size, patient characteristics, and reference tests used for validation. Many papers failed to report on the consecutiveness of patient inclusion, time between aphasia onset and administration of the screening test, and blinding. Of the three studies that were rated as having an intermediate or low risk of bias, the DOR was highest for the Language Screening Test and ScreeLing. Several screening tools for aphasia in stroke are available, but many tests have not been verified properly. Methodologically sound validation studies of aphasia screening tests are needed to determine their usefulness in clinical practice.