Fabienne Staub

Fatigue after Stroke: A Major but Neglected Issue

Subjective fatigue, defined as a feeling of early exhaustion developing during mental activity, with weariness, lack of energy and aversion to effort, remains virtually unstudied in patients with stroke, bur recent surveys suggest that it is a major, commonly overlooked, stroke sequela. While the few existing series did not show significant correlations between fatigue and stroke severity, lesion location, cognitive and neurological impairment and depression, recent neurobehavioral studies have highlighted an association between fatigue and brainstem and thalamic lesions. This suggests that fatigue may be linked to the interruption of neural networks involved in tonic attention, such as the reticular activating system. In fact, several subtypes of fatigue may develop after stroke, in connection with cognitive sequelae, neurological impairment, psychological factors and sleep disorders. A challenge is to identify and delineate these different subtypes and to distinguish them from mood disorders, which frequently coexist. We emphasize the concept of ‘primary’ poststroke fatigue, which may develop in the absence of depression or a significant cognitive sequela, and which may be linked to attentional deficits resulting from specific damage to the reticular formation and related structures involved in the subcortical attentional network. In the patients with excellent neurological and neuropsychological recovery, poststroke fatigue may be the only persisting sequela, which may severely limit their return to previous activities. The recognition of poststroke fatigue may be critical during recovery and rehabilitation after stroke.

Emotions, behaviours and mood changes in stroke.

The brain mediates and integrates all cognitive activities, emotional experiences and finally behaviours. Stroke is undoubtedly a privileged disease for human behavioural studies, because of its high incidence. Recent advances in high‐resolution magnetic resonance imaging techniques and functional neuroimaging allow both the precise localization of lesions and on‐line visualization of the activity of cerebral areas and networks. Nevertheless, the neuropsychiatry of stroke remains uncertain in its relationship with brain dysfunction. Clinical studies on registry populations, single case studies, and functional neuroimaging data provide interesting findings, but differences in methods and great individual intervariability still prevent a complete understanding of emotional perception and behavioural responses in stroke. We adopted an anatomical‐functional model as an operational framework in order to systematize the recent literature on emotional, behavioural and mood changes after stroke. The dysfunction of the areas subserving fundamental and executive functions induces behavioural and affective changes (such as depression, anxiety, apathy) that reflect the dysfunction of the whole system. Conversely, lesions in the system of instrumental functions induce signature syndromes (aphasia, anosognosia). At any delay from stroke, the diagnosis and treatment of mood and behavioural changes are a priority for clinicians and healthcare professionals to improve the quality of life of patients. Curr Opin Neurol 15:57–69.

Poststroke fatigue following minor infarcts: A prospective study

Objective: To explore the potential relationship between fatigue following strokes and poststroke mood, cognitive dysfunction, disability, and infarct site and to determine the predictive factors in the development of poststroke fatigue (PSF) following minor infarcts. Methods: Ninety-nine functionally active patients aged less than 70 years with a first, nondisabling stroke (NIH Stroke Scale score ≤6 in acute phase and ≤3 after 6 months, modified Rankin Scale score ≤1 at 6 months) were assessed during the acute phase and then at 6 (T1) and 12 months (T2) after their stroke. Scores in the Fatigue Assessment Inventory were described and correlated to age, gender, neurologic and functional impairment, lesion site, mood scores, neuropsychological data, laboratory data, and quality of life at T1 and T2 using a multivariate logistic regression analysis in order to determine which variables recorded at T1 best predicted fatigue at T2. Result: As many as 30.5% of the patients at T1 and 34.7% at T2 (11.6% new cases between T1 and T2) reported fatigue. At both 6 and 12 months, there was a significant association between fatigue and a reduction in professional activity. Attentional-executive impairment, depression, and anxiety levels remained associated with PSF throughout this time period, underlining the critical role of these variables in the genesis of PSF. There was no significant association between the lesion site and PSF. Conclusion: This study suggests that attentional and executive impairment, as well as depression and anxiety, may play a critical role in the development of PSF.

Post-Stroke Depression or Fatigue?

Accessible online at: www.karger.com/journals/ene Fatigue is a common complaint in clinical practice. It is a frequent symptom in patients with depression and other psychiatric disorders, cancer, inflammatory, endocrinologic and rheumatologic diseases. It may also develop without any other antecedent condition than a viral infection, leading to what is generally known as the ‘chronic fatigue syndrome’. In neurology, most studies have been performed in multiple sclerosis, but there are some investigations on fatigue in Parkinson’s disease, postpolio syndrome, immune-mediated polyneuropathies, systemic lupus erythematosus, Lyme disease and amyotrophic lateral sclerosis. Although fatigue is a frequent, often disabling, poststroke sequela, there have been only a few investigations on the subject [1–3]. Furthermore, fatigue was usually addressed just as one symptom of poststroke depression. This is why the study by van der Werf et al. in the present issue of European Neurology is particularly timely. The first issue to resolve is a definition problem. Indeed, although there is a popular knowledge of fatigue, the vagueness which surrounds the concept makes difficult any operational definition. The first and most obvious distinction is between objective and subjective fatigue. Objective fatigue is the observable and measurable decrement in performance occurring with the repetition of a physical or mental task, while subjective fatigue is a feeling of early exhaustion, weariness and aversion to effort. In their paper, van der Werf et al. have chosen the term of ‘experienced fatigue’ to describe this feeling of fatigue, which is indeed most relevant to clinical studies. It can also be useful to distinguish between fatigue which develops in connection with activities requiring a sustained effort (fatigability), and fatigue as a primary state which is closer to a lack of initiative with imbalance between motivation (preserved) and effectiveness (decreased). It is also possible to divide the concept of fatigue into various subtypes, namely ‘physical’ fatigue occurring after muscular exertion, ‘somatic’ fatigue related to disease, ‘mental’ fatigue (for example appearing with cognitively demanding tasks or in the presence of neuropsychological disorders) and ‘psychological’ fatigue (for example associated with lack of interest or poor motivation). These subtypes of fatigue (which are not mutually exclusive) can then be expressed at a behavioral level (objective fatigue) or as a state of feeling (subjective fatigue). The limit between normal and pathological fatigue is not clear. The duration (‘chronicity’) and severity of fatigue, associated disability (interference with daily functioning), other symptoms and the request for a medical consultation are signs which point towards an abnormal situation. Van der Werf et al. found that 51% of their stroke outpatients experienced severe fatigue against only 16% of the controls. This difference was also found by Ingles et al. [1], but with a higher proportion of selfreported fatigue problems (68% vs. 36%). In our own experience, poststroke fatigue is often quantitatively and qualitatively different from premorbid fatigue, which is in agreement with studies on fatigue in Parkinson’s disease [4] and multiple sclerosis [5].

Effect of modafinil on subjective fatigue in multiple sclerosis and stroke patients.

Background: Modafinil has anecdotal response to neurological fatigue, but such an effect may depend on the type and location of cerebral impairment. Objectives: It was the aim of this study to compare fatigue observed in different neurological pathologies, to evaluate the tolerability to modafinil, and to describe changes in subjective fatigue. Methods: We enrolled 14 brainstem or diencephalic stroke (BDS) patients, 9 cortical stroke (CS) patients and 17 multiple sclerosis (MS) patients. The Fatigue Assessment Instrument severity scale was performed at baseline, after 3 months of modafinil and after 1 month of washout. Cognition, mood and somnolence were assessed. A subgroup of 14 patients underwent activity measures before and during treatment. Results: Thirty-one patients completed the study (10 BDS, 9 CS, 12 MS). The responder profile is more frequent in MS than in CS (p = 0.04), and in BDS than in CS patients (p = 0.04). Actiwatch measures showed no changes in activity during, before and after therapy. Conclusion: Modafinil was tolerated in 75% of patients at small doses and seemed to improve the severity of fatigue in the MS and BDS groups but not in the CS group. There was no modification in measured physical activity.

Frequency, characterisation and therapies of fatigue after stroke

Post-stroke objective or subjective fatigue occurs in around 50% of patients and is frequent (30%) even after minor strokes. It can last more than one year after the event, and is characterised by a different quality from usual fatigue and good response to rest. Associated risk factors include age, single patients, female, disability, depression, attentional impairment and sometimes posterior strokes, but also inactivity, overweight, alcohol and sleep apnoea syndrome. There are few therapy studies, but treatment may include low-intensity training, cognitive therapy, treatment of associated depression, wakefulness-promoting agents like modafinil, correction of risk factors and adaptation of activities.

Is poststroke depression a vascular depression

As we learn more about the relationships between depression and cerebrovascular disease (CVD), a complex picture is emerging in which the chain of causality seems to spiral on itself: progressive or focal brain damage, cognitive impairment, depressive symptoms, dementia, and cardiovascular diseases, all seem to be liable to lead to one or another. Stroke may lead to depression, and the inverse may also be true. Depression may lead to cognitive impairment and cardiovascular diseases, which in turn may lead to subtle brain impairment, thereby causing more depression and cognitive impairments, and so on. In this presentation, we provide a rapid glance at the complexities of such issues.

Dimensions multiples de la fatigue d’origine neurologique : différences entre l’accident vasculaire cérébral et la sclérose en plaques

Resume Introduction La fatigue se definit par une difficulte a maintenir une activite mentale ou physique de maniere performante. Cette etude a pour but de demontrer l’aspect pluridimensionnel de ce symptome en comparant les caracteristiques de la fatigue sur deux groupes de patients souffrant d’affections neurologiques differentes mais ayant un handicap neurologique faible et comparable : un groupe de patients AVC (accident vasculaire cerebral mineur) et un groupe de patients SEP (sclerose en plaques). Methodes Le groupe AVC etait compose de 79 patients, dont le score a l’echelle du « National Institute of Health Stroke » (NIHSS) etait inferieur a 3 un an apres l’AVC, et le groupe SEP de 39 patients dont le diagnostic avait ete pose depuis moins de 5 ans, avec un score inferieur a 3 a l’« Expanded Disability Status Scale » (EDSS). Tous les patients ont repondu a un questionnaire d’auto-evaluation de la fatigue, le « Fatigue Assessment Instrument » (FAI). Ils n’etaient ni deprimes ni anxieux, et les deux groupes etaient apparies pour le deficit fonctionnel, le handicap et les sequelles cognitives. Resultats 29 p. 100 des patients AVC et 46 p. 100 des patients SEP (p Discussion Ces resultats confirment l’existence d’une fatigue d’origine cerebrale dans les deux populations, mesurable par des questionnaires adaptes. Elle est plus frequente et plus severe dans le groupe SEP. L’impact psychique et mental de cette fatigue est plus marque dans le groupe SEP, alors que les consequences physiques, professionnelles et sociales sont identiques dans les deux populations.

Emotional Disturbances after Stroke

Impairment after stroke may have acute and long-lasting psychological implications. Additionally, organic brain dysfunction also appears to play an important role in poststroke affective modifications. Emotional state is multidetermined and can be specifically modified by alteration of some brain networks. This article illustrates a certain number of acute and more chronic emotional disturbances after stroke, such as mood disorders, emotional dyscontrol, and modification of emotional experiences. Some neural mechanisms implicated in these modifications are discussed. The main modifications described are depression anxiety, psychosis, modification of emotional experience, and fatigue.