Journal of Psychosomatic Research 63 (2007) 539–544

Short communication

Fatigue after stroke: The development and evaluation of a case definition☆

Joanna Lyncha, Gillian Meada,⁎, Carolyn Greiga, Archie Younga,Susan Lewisa, Michael Sharpeb

aGeriatric Medicine, School of Clinical Sciences and Community Health, University of Edinburgh, New Royal Infirmary of Edinburgh,Edinburgh, Scotland, United Kingdom

bDivision of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, Scotland, United Kingdom

Received 8 February 2007; received in revised form 9 August 2007; accepted 9 August 2007

Abstract

Objective:While fatigue after stroke is a common problem, it hasno generally accepted definition. Our aim was to develop a casedefinition for post-stroke fatigue and to test its psychometricproperties. Methods: A case definition with face validity and anassociated structured interview was constructed. After initialpiloting, the feasibility, reliability (test–retest and inter-rater) andconcurrent validity (in relation to four fatigue severity scales) weredetermined in 55 patients with stroke. Results: All participatingpatients provided satisfactory answers to all the case definition probe

There are no competing interests. Approval was obtained from LothianResearch Ethics Committee.

☆ This study was funded by the Chief Scientist Office of the ScottishExecutive (reference CZG/2/161).

⁎ Corresponding author. Geriatric Medicine, School of ClinicalSciences and Community Health, University of Edinburgh, Room F1424,New Royal Infirmary of Edinburgh, EH16 4SA Edinburgh, Scotland, UnitedKingdom. Tel.: +44 0131 242 6481.

E-mail address: gillian.e.mead@ed.ac.uk (G. Mead).

0022-3999/07/$ – see front matter © 2007 Elsevier Inc. All rights reserved.doi:10.1016/j.jpsychores.2007.08.004

questions demonstrating its feasibility For test–retest reliability,kappa was 0.78 (95% CI, 0.57–0.94, Pb.01) and for inter-raterreliability kappa was 0.80 (95% CI, 0.62–0.99, Pb.01). Patientsfulfilling the case definition also had substantially higher fatiguescores on four fatigue severity scales (Pb.001) indicating concurrentvalidity. Conclusion: The proposed case definition is feasible toadminister and reliable in practice, and there is evidence of concu-rrent validity. It requires further evaluation in different settings.© 2007 Elsevier Inc. All rights reserved.

Keywords: Fatigue; Stroke; Reliability; Interview; Case definition

Background

Fatigue has been well-studied in neurological diseasessuch as multiple sclerosis [1]. Emerging evidence suggeststhat fatigue is common after stroke, even in patients whomake a full neurological recovery [2]; it is distressing [3];and it may predict fatality [4].

Currently, there is no valid and reliable definition ofpost-stroke fatigue, which is accepted by patients, clin-

icians, and researchers. Previous studies used scalesdevised and tested in nonstroke patients. They either useda single question [4,5] or a score above or below aparticular point on the chosen scale to define fatigue[3,6–8]. This approach does not necessarily detectclinically significant fatigue, i.e., fatigue which warrantsinvestigation and treatment. A case definition for clinicallysignificant fatigue would guide clinicians in the identifica-tion of fatigue after stroke and would allow researchers toobtain meaningful estimates of fatigue prevalence. Such anapproach has already been applied to idiopathic chronicfatigue [9] and cancer fatigue [10]. Case definitions havebeen proposed for post-stroke fatigue [2,11] but lack dataon their validity, feasibility of administration and reliabilityof case ascertainment.

Our aims were (1) to develop a simple, workable casedefinition for clinically significant fatigue after stroke withface validity, which could be easily applied in practice usinga brief interview; (2) to test its feasibility of administration,

540 J. Lynch et al. / Journal of Psychosomatic Research 63 (2007) 539–544

reliability (test–retest and inter-rater), and concurrentvalidity (i.e., “Do cases show more severe scores on fatiguescales then noncases?”); and (3) to describe the character-istics of patients identified by this definition.

Methods

Development of case definition

We set out to develop a case definition with face validity.In order to do this, we first scrutinized the previouslypublished case definitions [2,11]. Second, we reviewed datafrom a study of the frequency of fatigue (using the fatigueseverity scale) in stroke inpatients [8]. Third, we thematicallyanalysed qualitative interviews of four stroke inpatients withfatigue who were undergoing stroke rehabilitation. Thisthree-pronged approach indicated that patients' experienceof fatigue was predominantly physical rather than mental andthat, for fatigue to be clinically relevant, it had to interferewith daily activities.

A preliminary case definition and an associated interviewwas constructed and then piloted in 13 stroke inpatients. Wefound that probe questions were required to: (a) elicitrelevant information, (b) distinguish disability caused by theneurological effects of the stroke (e.g., hemiparesis) anddisability caused by fatigue, and (c) distinguish fatigue fromlack of motivation, apathy, and boredom.

The final version had two components: first, patientshad to report significant fatigue, and second, this fatiguehad to interfere with activities of daily living (Appendix).The different versions for hospital and communitypatients allowed for differences in the time elapsed sincestroke (Appendix).

Table 1Characteristics of inpatients and community patients

Inpatients(n=40)

C(n

Median age (IQR) 76.5 (67.3–81.8) 71Male (%) 21 (53) 10Right hemisphere stroke (%) 21 (53) 6Haemorrhagic stroke (%) 3 (8) 0TACS (%) 10 (25) 1PACS 17 (43) 5LACS 9 (23) 7POCS 4 (10) 2Relevant lesion on computed tomography (%) 33 (83) 10Median HADS anxiety score (IQR) 8 (6–12 e) 6Median HADS depression score (IQR) 8 (5–11 e) 6Fatigued on case definition (%) 16 (40) 4

Figures in parentheses show percentage (except for IQRs where indicated). TACsyndromes; LACS, lacunar syndromes; POCS, posterior circulation syndromes.

a Mann–Whitney U test.b Fisher's Exact Test.c Exact chi-squared test.d No data for two casese No data for one case—did not complete HADS due to distress.

Feasibility, reliability, and concurrent validity of thecase definition

Patient recruitment and inclusion criteriaOver 4 months, the research assistant visited two stroke

units (one acute and one rehabilitation) at least once a week,identified patients admitted with a new stroke and askednursing staff for permission to approach any patient withoutexclusion criteria. Community patients were identified bycommunity stroke nurses (who visit patients discharged fromstroke units) and from two outpatient stroke clinics. Writteninformed consent was obtained before recruitment.

Exclusion criteriaPatients who were medically unstable because of another

condition and those with dysphasia or confusion severeenough to prevent them from understanding the require-ments of participation were excluded.

Patient interviewsThe case definition interview (see Appendix) was

administered to determine whether the patient fulfilledcriteria. The first interview was audio-recorded for re-ratingby a second rater.

Feasibility. We recorded how many patients were able tounderstand and provide satisfactory answers to the casedefinition interview questions.Test–retest reliability. The case definition interview wasrepeated by the same interviewer 4 days later.Inter-rater reliability. The recordings of the first interviewwere re-rated by a rater who did not know the initial rating.Concurrent validity. Four scales to measure fatigueseverity [Short Form 36 (SF-36) vitality component

ommunity patients=15)

Total(n=55)

Comparison of inpatientsand community patients (P)

(61–79) 73 (66–81) .29 a

(67) 31 (56) .38 b

(40) 27 (49) .55 b

3 (6) .55 b

(7) 11 (20) .23 c

(33) 22 (40)(47) 16 (29)(13) 6 (11)(77 d) 43 (81) .69 b

(2–8) 7 (4–11) .01 a

(3–9) 7.5 (3–10) .10 a

(27) 20 (36) .53 b

S, total anterior circulation syndromes; PACS, partial anterior circulation

Fig. 1. Comparison of distribution of fatigue scale scores for cases & noncases. Horizontal lines show median, quartiles and range. o, outlier; *Extreme value.P values are for Mann–Whitney U tests.

541J. Lynch et al. / Journal of Psychosomatic Research 63 (2007) 539–544

[12], multidimensional fatigue symptom inventory (gen-eral component) [13], profile of mood states (fatiguecomponent) [14] and the Fatigue Assessment Scale [15]]were applied, and then scores were related to casedefinition fulfillment. Test–retest and inter-rater reliabilityof these four scales in stroke patients are reportedelsewhere [16].

Characteristics of patients identified by the case definition

Stroke subtype, side of brain lesion, and computedtomography were recorded from the case notes. The HospitalAnxiety and Depression Scale (HADS) was administered atthe first interview [17].

Analysis

SPSS version 14 was used (SPSS Inc., Chicago, IL,USA). Mann–Whitney U and Fisher's Exact and Exact chi-

squared tests were used as appropriate to compare thecharacteristics of inpatients with community patients andalso patients fulfilling case definition with those who did not.Cohen's kappa measured agreement between tests andbetween raters, with interpretation based on publishedguidelines [18]. Concurrent validity of the case definitionwas assessed using box plots and Mann–Whitney U tests toshow the relationship with the four fatigue severity scales.

Results

Patients

Sixty-four eligible patients were invited to participate; 55consented (Table 1). Median time between stroke and firstinterview was 23 days [interquartile range (IQR), 10–53] forinpatients and 137 days (IQR, 93–217) for communitypatients. The clinical characteristics of inpatients and

Table 2Characteristics of patients who meet the case definition compared with those who do not

Meet case definition(n=20)

Do not meetcase definition (n=35)

Total(n=55)

Comparison of positiveand negative definitions (P)

Median age (IQR) 70 (60–77) 77 (68–83) 73 (66–81) .06a

Male (%) 7 (35) 24 (69) 31 (56) .02b

Right hemisphere stroke (%) 12 (60) 15 (43) 27 (49) .27b

Haemorrhagic stroke (%) 2 (10) 1 (3) 3 (6) .55b

TACS (%) 5 (25) 6 (17) 11 (20) .74c

PACS 8 (40) 14 (40) 22 (40)LACS 6 (30) 10 (29) 16 (29)POCS 1 (5) 5 (14) 6 (11)Relevant lesion on CT (%) 15 (79 d) 28 (82 d) 43 (81) 1.0b

Median HADS anxiety score (IQR) 8.5 (6.3–13) 6.5 (3.8–8.3 d) 7 (4–11) .004a

Median HADS depression score (IQR) 9 (7–13) 7 (3–9 d) 7.5 (3–10) .006a

Inpatients (%) 16 (80) 24 (69) 40 (73) .53b

Figures in parentheses show percentage (except for interquartile ranges where indicated).a Mann–Whitney U test.b Fisher's Exact Test.c Exact chi-squared test.d No data for one case.

542 J. Lynch et al. / Journal of Psychosomatic Research 63 (2007) 539–544

community patients were similar except that inpatients weremore anxious (Table 1).

Fifty-five patients were successfully interviewed at Time1 and 51 at Time 2. Of the four who did not receive a secondinterview, one had been discharged, two had deterioratedmedically, and one refused. Mean time between interviewsfor test–retest reliability was 3.6 days.

Feasibility of case definition

At both interviews, all participating patients providedsatisfactory answers to all case definition probe questions.

Test–retest reliability

There was good test–retest agreement (kappa, 0.78; 95%CI, 0.60–0.96, n=51) between the first and the second casedefinition interview.

Inter-rater reliability

Of the audio-recorded case definition interviews, 43were analyzed. The remaining eight interviews were notanalysed due to technical difficulties with the taperecordings (3), the tape being unclear (3) and the secondobserver deciding that there was not enough information tomake a decision about case definition fulfillment (2). Ofthe 43 interviews analysed, kappa was 0.82 (very good)(95% CI, 0.64–0.99).

Concurrent validity

Fig. 1 shows that patients fulfilling the case definitiongenerally had substantially higher fatigue scores on all of thefour fatigue scales, suggesting good concurrent validity(Pb.001, Mann–Whitney U test). Note that lower scores on

the SF-36 (vitality component) indicate greater fatiguewhereas the reverse is true for the other three scales.

Clinical characteristics of cases

Twenty (36%) patients fulfilled the case definition at thefirst interview. “Caseness” was associated with femalegender and greater emotional distress (Table 2).

Discussion

Fatigue, like all symptoms, is essentially subjective andmay have a number of different causes. Nevertheless, it isimportant to have a working case definition to identify whichpatient can be regarded as having clinically significantfatigue, i.e., fatigue which warrants further investigationand treatment.

We developed the case definition by scrutiny of twoprevious case definitions, review of data from our pilot studyof stroke inpatients, and four qualitative interviews. Our newcase definition had face validity, the interview was feasible toadminister, it had good reliability, and case definitionfulfillment was associated with more severe fatigue scoreson four fatigue severity scales, demonstrating concurrentvalidity. Almost 40% of our patients fulfilled the casedefinition, a prevalence in the range of those previouslyreported (i.e., 16–70%) [3–8]. Caseness was associated withfemale gender and emotional distress but not with stroke type(Table 2). These associations require further investigation ina larger study.

This study had a number of limitations: firstly, a largersample size would have provided a more precise estimate ofreliability. However, our sample size has been consideredadequate for studies of this type [18]. Secondly, ethicalapproval stipulated that clinical staff had to make the initial

543J. Lynch et al. / Journal of Psychosomatic Research 63 (2007) 539–544

approach to patients, so patients known to be tired may havebeen approached more often and therefore overrepresented,reducing the range of fatigue severity in our sample.However, we emphasized to clinical staff that patients werepotentially eligible irrespective of whether or not they werefatigued. Thirdly, we relied on face validity and concurrentvalidity as there is currently no test for identifying fatigueafter stroke, making criterion validity impossible. We, did,however, demonstrate that patients fulfilling the casedefinition had higher scores on four fatigue severity scales(Fig. 1) [12–15]. Fourthly, when assessing test–retestreliability, the interviewer may have remembered theoutcome of the first interview when performing the second,a potential problem in all studies of test–retest reliability ofpatient interviews. Fifthly, the assessment of inter-rateragreement would have been more rigorous if the second raterhad repeated a face-to-face case definition interview and notmerely listened to a recording. Finally there are limitations tothe generalisability of our data. The sample we studied wasmainly of inpatients, and the nature of fatigue may changeafter discharge from hospital as patients' activities becomemore complex. We also excluded patients with dysphasia orconfusion for whom visual analogue scales or pictorialrepresentations of fatigue may be appropriate.

In summary a new case definition and interview forclinically significant post-stroke fatigue after stroke isproposed, which has face validity and concurrent validity,is feasible to administer, and is reliable in practice at least instroke inpatients without communication difficulties. Itsfurther evaluation in different samples, in different settings,and by different observers, is now required.

Acknowledgments

We are grateful to the patients who participated in thestudy, the nursing staff who assisted us in identifyingpatients, and the stroke physicians who allowed us to studypatients under their care.

References

[1] Wessely S, Hotopf M, Sharpe M. Chronic fatigue and its syndromes.New York: Oxford University Press, 1998.

[2] Staub F, Bogousslavsky J. Fatigue after stroke: a major but neglectedissue. Cerebrovasc Dis 2001;12:75–81.

[3] Van der Werf SP, Van den Broek HL, Anten HW, Bleijenberg G.Experience of severe fatigue long after stroke and its relation to depressivesymptoms and disease characteristics. Eur Neurol 2001;45:28–33.

[4] Glader E-L, Stegmayr B, Asplund K. Post-stroke fatigue. A 2 yearfollow-up study of Stroke Patients in Sweden. Stroke 2002;33:1327–33.

[5] Leegaard OF. Diffuse cerebral symptoms in convalescents fromcerebral infarction and myocardial infarction. Acta Neurol Scand 1983;67:348–55.

[6] Ingles JL, Eskes GA, Phillips SJ. Fatigue after stroke. Arch Phys MedRehab 1999;80:173–8.

[7] Carlsson GE, Moller A, Blomstrand C. Consequences of mild strokein persons b75 years—a 1-year follow-up. Cerebrovasc Dis 2003;16:383–8.

[8] Morley W, Jackson K, Mead G. Fatigue after stroke: neglected butimportant. Age Ageing 2005;34:313.

[9] Fukada K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A.International Chronic Fatigue Syndrome Study Group. Ann InternMed1994;121:953–9.

[10] Sadler IJ, Jacobsen PB, Booth-Jones M, Belanger H, Weitzner MA,Fields KK. Preliminary evaluation of a clinical syndrome approach toassessing cancer-related fatigue. J Pain Symptom Manage 2002;23:406–16.

[11] de GrooMH, Phillips SJ, Eskes GA. Fatigue associated with stroke andother neurologic conditions: implications for stroke rehabilitation.Arch Phys Med Rehab 2003;84:1714–20.

[12] Medical Outcomes Trust. SF-36 health survey: scoring manual forEnglish language adaptations. Boston (MA): Medical Outcomes Trust,1994.

[13] McNair DM, Lorr M. An analysis of mood in neurotics. J Abnorm SocPsychol 1964;69:620–7.

[14] Michielsen HJ, De Vries J, Van Heck GL. Psychometric qualities of abrief self-rated fatigue measure. The Fatigue Assessment Scale.J Psychosom Res 2003;54:345–53.

[15] Stein KD, Martin SC, Hann DM, Jacobsen PB. A multidimensionalmeasure of fatigue for use with cancer patients. Cancer Pract 1998;6:143–52.

[16] Mead GE, Lynch J, Greig C, Young A, Lewis SJ, Sharpe M. Anevaluation of fatigue scales in stroke patients. Stroke 2007;38:2090–5.

[17] Sigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale.Acta Psychiatr Scand 1983;67:361–70.

[18] Altman DG. Practical statistics for medical research. London:Chapman and Hall, 1991.

Appendix

1. Post-stroke fatigue case definition—community patients

Over the past month, there has been at least a 2-weekperiod when patient has experienced fatigue, a lack ofenergy, or an increased need to rest every day or nearlyevery day.

This fatigue has led to difficulty taking part in everydayactivities.

2. Post-stroke fatigue case definition—hospital patients

Since their stroke, the patient has experienced fatigue, alack of energy, or an increased need to rest every day or nearlyevery day.

This fatigue has led to difficulty taking part in everydayactivities (for inpatients this may include therapy and mayinclude the need to terminate an activity early becauseof fatigue).

3. Structured interview schedule for community patients

1a) Over the past month, have you experienced fatigue,

a lack of energy or an increased need to rest?

1bi) Can you describe what your fatigue feels like, inyour own words?

1bii) Is it a sleepy feeling, or is it more a lack of energy?1ci) Over the past month, how much of the time do you

feel fatigued?

1cii) How much of the day do you feel fatigued?2a) Do you feel that fatigue is a problem for you?

Pro

544 J. Lynch et al. / Journal of Psychosomatic Research 63 (2007) 539–544

2b) Is there anything else about your experience of

be C

fatigue that you feel is important?

riteria

Score

1a

Patient must answer yes to this question to fulfil thecase definition. If patient answers no, go straight toquestion 2a.

Yes/no

1bi

Patient should describe feelings which are consistentwith fatigue or lack of energy or increased need to restrather than lack of motivation or boredom.

Yes/no

1bii

Patients should describe feelings of fatigue (or lack ofenergy or increased need to rest) rather than sleepiness

Yes/no

1ci)

Fatigue should have been present everyday or nearlyeveryday for at least two weeks in past month.

Yes/no

1cii)

Fatigue must be present forN50% of waking hours Yes/no 2a Fatigue must be perceived as a problem and affect

everyday activities, e.g., activities of daily living,recreational activities such as reading or watching thetelevision, and may or may not affect participation intherapy.

Yes/no

2b

Please note the patient's response.

All questions must be scored yes for the case definition tobe fulfilled (except for 1bi where the interviewer can make ajudgement about the presence of fatigue in patients whocannot articulate their feelings clearly).

4. Guidance for interpretation of post-stroke fatigue casedefinition probe questions

1a) Patient must answer yes in order to fulfil case

definition.

1bi) The patient should describe feelings of tiredness,

lack of energy or fatigue or increased need to rest(e.g., I just feel tired all the time) as opposed to lackof motivation (e.g., I just can't be bothered doinganything) or boredom (e.g., I just fall asleep all thetime because there's nothing to do). However, thisquestion can be scored no and the case definition befulfilled as some patients may be unable to describehow they feel (e.g., simply inarticulate).

1bii) This question should be asked if the interviewer is

not satisfied that the description is one of fatigue asopposed to sleepiness. If patients describe onlysleepiness, they do not fulfil the definition.

1ci) The patient should have felt fatigue everyday or

nearly everyday for at least 2 weeks in the pastmonth. If a patient answers “all the time,” probefurther with “Do you feel fatigued everyday, or is itless often?”

1cii) This question should be put to patients who feel that

the fatigue is present everyday or nearly everyday in

the past two weeks. If patient is unsure, probe with,e.g., “Is the fatigue present all day, or do you think itcomes on at certain times of the day?” To fulfil thedefinition, fatigue has to be present for more than50% of waking hours.

2a) Fatigue must be perceived as a problem and affect

everyday activities (e.g., activities of daily living,reading or watching television, physiotherapy). Ifpatient just answers “yes,” probe further with “Canyou give me an example of how fatigue is a problemfor you?” or “Can you give me an example ofsomething fatigue has affected or stopped you fromdoing.” If patient cannot give an example probefurther with “Does fatigue affect your ability to read orwatch television, or to take part in physiotherapy forexample?” If a patient answers, e.g., “reading,” ask“And how does fatigue affect your reading?” If apatient reports that their walking is affected by fatigue,and that patient has a hemiparesis, the interviewershould ask, e.g., “Anddoyou think that fatigue aswellas your weak leg affects your walking?”The interviewer may make a judgement that fatigue isa problem, even when the patient denies it. Forexample, if a patient reports that they can still carry outeveryday activities but that everything is a struggle, orthat they force themselves to continue with things, theinterviewer may wish to probe further asking “Why iseverything a struggle?” If the interviewer believes thatfatigue affects everyday activities, even though thepatient is able to complete them, he or she shouldscore this question yes. If on the other hand, the patienthas adapted his or her lifestyle in order to accom-modate fatigue, and does not view this adaptation as aproblem, then this question should be scored no. If thepatient says that fatigue affects their mood, and this inturn affects their participation in activities, then thisquestion should be scored yes.

2b) This question does not have a score, as it is simply

an opportunity for the patient to bring to theattention of the interviewer anything about theirexperience of fatigue which has not been covered bythe probe questions. It may also be useful forclarification of the patient's experience of fatigue.NB: All additional probe questions given inguidance notes are intended as a guide, questionsmay be adapted to each patient, or the interviewermay ask his or her own additional questions to elicitthe necessary information.NB: For hospital patients, “over the past month” ischanged to “since your stroke.”