Sieberen P. van der Werf

Experience of Severe Fatigue Long after Stroke and Its Relation to Depressive Symptoms and Disease Characteristics

Although the experience of abnormal fatigue is recognised as a major disabling symptom in many chronic neurological diseases, little is known about the persistence of severe fatigue after an abrupt neurological incident like a stroke. Therefore, the objectives of this study were to test whether the experience of severe fatigue persists long after a stroke has occurred, and to assess the relation between experienced fatigue and levels of physical impairment and depression. Ninety stroke outpatients and 50 controls returned mailed questionnaires. Compared to age-matched controls, a significantly larger proportion (16 vs. 51%) of the stroke respondents experienced severe fatigue, while 20% of the patients and 16% of the controls had elevated depression symptom scores. The time which had elapsed since the stroke occurred could not explain levels of fatigue. In the control group, the number of depressive symptoms explained most of the variance in levels of fatigue, while impairment of locomotion explained most of the variance in the stroke group.

Fatigue in disease-free cancer patients compared with fatigue in patients with Chronic Fatigue Syndrome

Abstract The goal of our work was to assess fatigue in disease-free cancer patients with help of a validated fatigue questionnaire. Furthermore, we wished to analyse the relationship between severe fatigue and former treatment modalities, problems of concentration and motivation, physical activity, functional impairment, depression and anxiety and finally, to compare severely fatigued disease-free cancer patients and patients with Chronic Fatigue Syndrome (CFS). The participants were 85 adult cancer patients and 16 patients with CFS. The cancer patients were all disease-free and had been off treatment for a minimum of 6 months. They were asked to participate in this study by their physician when they came to the hospital for control visits. Patients who were willing to participate completed four questionnaires. The Checklist Individual Strength was used to measure fatigue. In addition, the Beck Depression Inventory, the Spielberger Trait Anxiety Inventory and the Nottingham Health Profile were used. Results indicate that 19% of the disease-free cancer patients were severely fatigued. Their fatigue experience is comparable to that of patients with CFS. Severe fatigue is associated with problems of concentration and motivation, reduced physical activity, emotional health problems and pain. Furthermore, a relation was found between fatigue and depression and anxiety. No relation was found between fatigue and type of cancer, former treatment modalities, duration of treatment and time since treatment ended. In conclusion, for one fifth of a group of disease-free cancer patients fatigue is a severe problem long after treatment. In addition to fatigue, these patients experience several psychological and physical problems.

Recovery from mild traumatic brain injury: a focus on fatigue.

BackgroundFatigue is one of the most frequently reported symptoms after Mild Traumatic Brain Injury (MTBI). To date, systematic and comparative studies on fatigue after MTBI are scarce, and knowledge on causal mechanisms is lacking.ObjectivesTo determine the severity of fatigue six months after MTBI and its relation to outcome. Furthermore, to test whether injury indices, such as Glasgow Coma Scale scores, are related to higher levels of fatigue.MethodsPostal questionnaires were sent to a consecutive group of patients with an MTBI and a minor-injury control group, aged 18–60, six months after injury. Fatigue severity was measured with the Checklist Individual Strength. Postconcussional symptoms and limitations in daily functioning were assessed using the Rivermead Post Concussion Questionnaire and the SF-36.ResultsA total of 299 out of 618 eligible (response rate 52%) MTBI patients and 287 out of 482 eligible (response rate 60%) minor-injury patients returned the questionnaire. Ninety-five MTBI patients (32%) and 35 control patients (12%) were severely fatigued. Severe fatigue was highly associated with the experience of other symptoms, limitations in physical and social functioning, and fatigue related problems like reduced activity. Of various trauma severity indices, nausea and headache experienced on the ED were significantly related to higher levels of fatigue at six months.ConclusionsIn conclusion, one third of a large sample of MTBI patients experiences severe fatigue six months after injury, and this experience is associated with limitations in daily functioning. Our finding that acute symptoms and mechanism of injury rather than injury severity indices appear to be related to higher levels of fatigue warrants further investigation.

Natural course and predicting self-reported improvement in patients with chronic fatigue syndrome with a relatively short illness duration

OBJECTIVE To describe the course of fatigue in chronic fatigue syndrome (CFS) patients with a relatively short duration of complaints and to test which psychosocial factors predict spontaneous improvement 1 year later. METHODS Seventy-nine patients with a complaint duration of less than 2 years were tested at baseline and 78 of the same group at 1-year follow-up. During this time period, no systematic intervention took place. Self-reported improvement and fatigue severity were the main outcome measures. RESULTS Forty-six percent (95% confidence intervals, 95CI = 35-58%) of the patients with a short illness duration reported to be improved. This was a significantly (chi(2) = 20.3, P < .001) higher percentage compared to the 20% (95CI = 15-26%) self-reported improvement in a previously published natural-course study among 246 CFS patients with a longer illness duration. Persistence of complaints after 1-year follow-up was associated with high baseline levels of experienced concentration problems, less strong psychosocial causal explanations for the complaints, and higher levels of the experienced lack of social support. Baseline fatigue severity predicted fatigue severity at follow-up. CONCLUSION The results showed that CFS patients with a relatively short duration of complaints had a more favourable outcome compared to patients with a long illness duration. The data also indicated that complete recovery only occurred in patients with a complaint duration of less than 15 months. This finding has important implications, since it suggests that after such a time period spontaneous recovery hardly occurs.

Endotoxemia-induced inflammation and the effect on the human brain

IntroductionEffects of systemic inflammation on cerebral function are not clear, as both inflammation-induced encephalopathy as well as stress-hormone mediated alertness have been described.MethodsExperimental endotoxemia (2 ng/kg Escherichia coli lipopolysaccharide [LPS]) was induced in 15 subjects, whereas 10 served as controls. Cytokines (TNF-α, IL-6, IL1-RA and IL-10), cortisol, brain specific proteins (BSP), electroencephalography (EEG) and cognitive function tests (CFTs) were determined.ResultsFollowing LPS infusion, circulating pro- and anti-inflammatory cytokines, and cortisol increased (P < 0.0001). BSP changes stayed within the normal range, in which neuron specific enolase (NSE) and S100-β changed significantly. Except in one subject with a mild encephalopathic episode, without cognitive dysfunction, endotoxemia induced no clinically relevant EEG changes. Quantitative EEG analysis showed a higher state of alertness detected by changes in the central region, and peak frequency in the occipital region. Improved CFTs during endotoxemia was found to be due to a practice effect as CFTs improved to the same extent in the reference group. Cortisol significantly correlated with a higher state of alertness detected on the EEG. Increased IL-10 and the decreased NSE both correlated with improvement of working memory and with psychomotor speed capacity. No other significant correlations between cytokines, cortisol, EEG, CFT and BSP were found.ConclusionsShort-term systemic inflammation does not provoke or explain the occurrence of septic encephalopathy, but primarily results in an inflammation-mediated increase in cortisol and alertness.Trial registrationNCT00513110.

Long-term pain, fatigue, and impairment in neuralgic amyotrophy.

OBJECTIVES Recently, it has become clear that neuralgic amyotrophy (NA; idiopathic and hereditary brachial plexus neuropathy) has a less optimistic prognosis than usually assumed. To optimize treatment and management of these patients, one needs to know the residual symptoms and impairments they suffer. Therefore, the objective of this study was to describe the prevalence of pain, psychologic symptoms, fatigue, functional status, and quality of life in patients with NA. SETTING Neurology outpatient department of an academic teaching hospital. PARTICIPANTS NA patients (N=89) were studied, and clinical details were recorded. Self-report data were on average collected 2 years after the onset of the last NA episode. MAIN OUTCOME MEASURES Pain was assessed with the McGill Pain Questionnaire, fatigue with the Checklist Individual Strength, and psychologic distress with the Symptom Checklist 90. Functional status and handicap were assessed with the modified Rankin Scale and Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS Pain was usually localized in the right shoulder and upper arm, matching the clinical predilection site for paresis in NA. About a quarter to a third of the patients reported significant long-term pain and fatigue, and half to two thirds still experienced impairments in daily life. Over one third of the individual patients suffered from severe fatigue. The group did not fulfill the criteria of chronic fatigue or major psychologic distress. There was no correlation of pain or fatigue with the level of residual paresis on a Medical Research Council scale, but patients with a comorbid condition fared worse than patients without. CONCLUSIONS A significant number of NA patients suffer from persistent pain and fatigue, leading to impairment. Symptoms were not correlated with psychologic distress. This makes it likely that they are caused by residual shoulder or arm dysfunction but not as part of a chronic pain or fatigue syndrome in these patients.

How mild traumatic brain injury may affect declarative memory performance in the post-acute stage

Memory deficits are among the most frequently reported sequelae of mild traumatic brain injury (MTBI), especially early after injury. To date, these cognitive deficits remain poorly understood, as in most patients the brain is macroscopically intact. To identify the mechanism by which MTBI causes declarative memory impairments, we probed the functionality of the medial temporal lobe (MTL) and the prefrontal cortex (PFC), within 6 weeks after injury in 43 patients from a consecutive cohort, and matched healthy controls. In addition to neuropsychological measures of declarative memory and other cognitive domains, all subjects underwent functional magnetic resonance imaging (fMRI). Behavioral results showed poorer declarative memory performance in patients than controls, and decreasing performance with increasing duration of post-traumatic amnesia (a measure of injury severity). Task performance in the scanner was, as intended by the task and design, similar in patients and controls, and did not relate to injury severity. The task used reliably activated the MTL and PFC. Although we did not find significant differences in brain activity when comparing patients and controls, we revealed, in agreement with our neuropsychological findings, an inverse correlation between MTL activity and injury severity. In contrast, no difference in prefrontal activation was found between patients and controls, nor was there a relation with injury severity. On a behavioral level, injury severity was inversely related to declarative memory performance. In all, these findings suggest that reduced medial temporal functionality may contribute to poorer declarative memory performance in the post-acute stage of MTBI, especially in patients with longer post-traumatic amnesia.

Neural correlates of strategic memory retrieval: differentiating between spatial-associative and temporal-associative strategies.

Remembering complex, multidimensional information typically requires strategic memory retrieval, during which information is structured, for instance by spatial‐ or temporal associations. Although brain regions involved in strategic memory retrieval in general have been identified, differences in retrieval operations related to distinct retrieval strategies are not well‐understood. Thus, our aim was to identify brain regions whose activity is differentially involved in spatial‐associative and temporal‐associative retrieval. First, we showed that our behavioral paradigm probing memory for a set of object‐location associations promoted the use of a spatial‐associative structure following an encoding condition that provided multiple associations to neighboring objects (spatial‐associative condition) and the use of a temporal‐associative structure following another study condition that provided predominantly temporal associations between sequentially presented items (temporal‐associative condition). Next, we used an adapted version of this paradigm for functional MRI, where we contrasted brain activity related to the recall of object‐location associations that were either encoded in the spatial‐ or the temporal‐associative condition. In addition to brain regions generally involved in recall, we found that activity in higher‐order visual regions, including the fusiform gyrus, the lingual gyrus, and the cuneus, was relatively enhanced when subjects used a spatial‐associative structure for retrieval. In contrast, activity in the globus pallidus and the thalamus was relatively enhanced when subjects used a temporal‐associative structure for retrieval. In conclusion, we provide evidence for differential involvement of these brain regions related to different types of strategic memory retrieval and the neural structures described play a role in either spatial‐associative or temporal‐associative memory retrieval. Hum Brain Mapp 2008.

Being homebound with chronic fatigue syndrome: A multidimensional comparison with outpatients

Many patients with chronic fatigue syndrome (CFS) seem to experience periods in which they are homebound due to their symptomatology. Despite a growing body of research about CFS, little is known about patients who no longer feel able to leave their homes. The purpose of the present study was to examine whether homebound patients differ from other CFS patients on illness-specific characteristics. Besides experiencing more impairment in daily functioning than participants of an outpatient intervention study, homebound patients were characterised by extremely high levels of daily fatigue, predominant somatic attributions, and pervasively passive activity patterns. The course of symptomatology was similarly stable in both groups. Our findings suggest that homebound patients form a distinct subgroup of CFS patients who might profit from a treatment approach that is tailored to their specific needs. The exploratory nature of this first systematic investigation of homebound CFS patients is stressed, and suggestions for future research are made.

Striatal dopamine and learning strategy-an (123)I-FP-CIT SPECT study.

UNLABELLED Patients with Parkinsons disease (PD) have difficulty in processing learning tasks that lack external guidelines and, consequently, necessitate the subjects to generate their own problem-solving strategy. While the contribution of striatal dopaminergic deficiency to PD-specific motor symptoms is well established, its role in the PD-characteristic deviant learning style remains unclear. The aim of this study was to assess the relation between striatal dopamine activity as revealed by single photon emission computed tomography (SPECT) with (123)I-FP-CIT, a ligand for the dopamine transporter (DaT), and type of learning strategy, as identified by the California Verbal Learning Task (CVLT) in 19 patients with probable PD. The results showed a robust inverse correlation between striatal dopamine DaT binding and the externally guided, serial learning strategy: the lower the DaT in caudate nucleus as well as in putamen, the more the patient group appeared to rely on externally structured learning. Additionally, a significant positive correlation was found between caudatal DaT activity and the internally generated, semantic learning strategy. Unlike these strategic learning characteristics, IQ equivalent and recall total score appeared to vary independently from striatal DaT availability. CONCLUSION our findings provide direct evidence that striatal dopaminergic activity is specifically involved in the regulation of strategic learning processes.