Bowen Neglect

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Cognitive rehabilitation for spatial neglect following stroke

(Review)

Bowen A, Lincoln NB

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published inThe Cochrane Library2007, Issue 3

http://www.thecochranelibrary.com

1Cognitive rehabilitation for spatial neglect following stroke (Review)

Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
http://www.thecochranelibrary.com/http://www.thecochranelibrary.com/


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T A B L E O F C O N T E N T S

1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW . . . . . . . . . . . . . . . . . .

3SEARCH METHODS FOR IDENTIFICATION OF STUDIES . . . . . . . . . . . . . . . . . . .

6METHODS OF THE REVIEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

7DESCRIPTION OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

8METHODOLOGICAL QUALITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

9RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

10DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

11AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

11POTENTIAL CONFLICT OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . .

12ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

15TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15Characteristics of included studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

25Characteristics of excluded studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

26Characteristics of ongoing studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

28ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

28Comparison 01. Cognitive rehabilitation versus any control: immediate effects . . . . . . . . . . . . .

28Comparison 02. Cognitive rehabilitation versus any control: persisting effects . . . . . . . . . . . . . .

29Comparison 03. One type of cognitive rehabilitation versus standard care or attention control: persisting effects . .

29Comparison 04. One cognitive rehabilitation approach versus another: persisting effects . . . . . . . . . .

29Comparison 05. Bottom-up processing approaches versus any control: persisting effects . . . . . . . . . .

29Comparison 06. Top-down processing rehabilitation approaches versus any control: persisting effects . . . . . .

29INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

29COVER SHEET . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

30GRAPHS AND OTHER TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .31Analysis 01.01. Comparison 01 Cognitive rehabilitation versus any control: immediate effects, Outcome 01 Activities of

Daily Living . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

32Analysis 01.02. Comparison 01 Cognitive rehabilitation versus any control: immediate effects, Outcome 02 Cancellation:

numbers correct . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

33Analysis 01.03. Comparison 01 Cognitive rehabilitation versus any control: immediate effects, Outcome 03 Cancellation:

numbers of errors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

33Analysis 01.04. Comparison 01 Cognitive rehabilitation versus any control: immediate effects, Outcome 04 Line

bisection: error scores/right deviation . . . . . . . . . . . . . . . . . . . . . . . . . .

34Analysis 01.05. Comparison 01 Cognitive rehabilitation versus any control: immediate effects, Outcome 05 BIT

behavioural subtests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

34Analysis 01.06. Comparison 01 Cognitive rehabilitation versus any control: immediate effects, Outcome 06 Discharge

destination (home) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

35Analysis 01.07. Comparison 01 Cognitive rehabilitation versus any control: immediate effects, Outcome 07 A-rated

studies only: Activities of Daily Living . . . . . . . . . . . . . . . . . . . . . . . . .


studies only: cancellation number correct (single letter task) . . . . . . . . . . . . . . . . . .


studies only: cancellation errors . . . . . . . . . . . . . . . . . . . . . . . . . . . .


studies only: BIT behavioural subtests . . . . . . . . . . . . . . . . . . . . . . . . .

iCognitive rehabilitation for spatial neglect following stroke (Review)



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37Analysis 02.01. Comparison 02 Cognitive rehabilitation versus any control: persisting effects, Outcome 01 Activities of

Daily Living . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

38Analysis 02.02. Comparison 02 Cognitive rehabilitation versus any control: persisting effects, Outcome 02 Cancellation:

number correct . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

38Analysis 02.03. Comparison 02 Cognitive rehabilitation versus any control: persisting effects, Outcome 03 Cancellation:

number of errors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

39Analysis 02.04. Comparison 02 Cognitive rehabilitation versus any control: persisting effects, Outcome 04 LineBisection: error scores or right deviation . . . . . . . . . . . . . . . . . . . . . . . . .

39Analysis 02.05. Comparison 02 Cognitive rehabilitation versus any control: persisting effects, Outcome 05 BIT

behavioural . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

40Analysis 02.06. Comparison 02 Cognitive rehabilitation versus any control: persisting effects, Outcome 06 A-rated

studies: Activities of Daily Living . . . . . . . . . . . . . . . . . . . . . . . . . . .


studies only: cancellation number of errors . . . . . . . . . . . . . . . . . . . . . . . .


studies only: BIT behavioural . . . . . . . . . . . . . . . . . . . . . . . . . . . .

41Analysis 03.01. Comparison 03 One type of cognitive rehabilitation versus standard care or attention control: persisting

effects, Outcome 01 Activities of Daily Living . . . . . . . . . . . . . . . . . . . . . . .

42Analysis 04.01. Comparison 04 One cognitive rehabilitation approach versus another: persisting effects, Outcome 01

Activities of Daily Living . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .42Analysis 05.01. Comparison 05 Bottom-up processing approaches versus any control: persisting effects, Outcome 01

Activities of Daily Living . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

43Analysis 06.01. Comparison 06 Top-down processing rehabilitation approaches versus any control: persisting effects,

Outcome 01 Activities of Daily Living . . . . . . . . . . . . . . . . . . . . . . . . .

iiCognitive rehabilitation for spatial neglect following stroke (Review)



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Cognitive rehabilitation for spatial neglect following stroke

(Review)

Bowen A, Lincoln NB

This record should be cited as:

Bowen A, Lincoln NB. Cognitive rehabilitation for spatial neglect following stroke. Cochrane Database of Systematic Reviews2007,Issue 2. Art. No.: CD003586. DOI: 10.1002/14651858.CD003586.pub2.

This version first published online:18 April 2007 in Issue 2, 2007.

Date of most recent substantive amendment:19 January 2007

A B S T R A C T

Background

Unilateral spatial neglect causes difficulty attending to one side of space. Various rehabilitation strategies have been used but evidence

of their benefit is lacking.

Objectives

To determine the persisting effects of cognitive rehabilitation specifically aimed at spatial neglect following stroke, as measured on

impairment and disability level outcome assessments and on destination on discharge from hospital.

Search strategy

We searched the Cochrane Stroke Group Trials Register (last searched 4 July 2005), MEDLINE (1966 to July 2005), EMBASE

(1980 to July 2005), CINAHL (1983 to July 2005), PsycINFO (1974 to July 2005), UK National Research Register (July 2005). We

handsearched relevant journals, screened reference lists, and tracked citations using SCISEARCH.

Selection criteria

We included randomised controlled trials of cognitive rehabilitation specifically aimed at spatial neglect. We excluded studies of generalstroke rehabilitation and studies with mixed patient groups, unless more than 75% of their sample were stroke patients or separate

stroke data were available.

Data collection and analysis

Two review authors independently selected trials, extracted data, and assessed trial quality.

Main results

We included 12 RCTs with 306 participants. Only four had adequate allocation concealment, that is a low risk of selection bias. A large

number of outcome measures were reported. Only six studies measured disability and two investigated whether the effects persisted.

The overall effect (standardised mean difference) on disability had a wide confidence interval that included zero and was not statistically

significant. For discharge destination there were clinically significant effects but in both directions and the confidence interval of the

odds ratio included one. In contrast, cognitive rehabilitation did improve performance on some, but not all, standardised neglect tests.

The number of cancellation errors made was reduced and the ability to find the midpoint of a line improved immediately and persisted

at follow up. These effects appeared likely to generalise from the samples studied to the target population, but were based on a smallnumber of studies.

Authors conclusions

Several types of neglect specific approaches are now described but there is insufficient evidence to support or refute their effectiveness

at reducing disability and improving independence. They can alter test performance and warrant further investigation in high quality

randomised controlled trials. As we did not review whether patients with neglect benefit from rehabilitation input in general, such

patients should continue to receive general stroke rehabilitation services.




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P L A I N L A N G U A G E S U M M A R Y

The benefit of cognitive rehabilitation for unilateral spatial neglect, a condition that can affect stroke survivors, is unclear

Unilateral spatial neglect is a condition which reduces a persons ability to look, listen or make movements in one half of their

environment. This can affect their ability to carry out many everyday tasks such as eating, reading and getting dressed, and restricts

a persons independence. Our review found that rehabilitation specifically targeted at neglect appeared to improve a persons ability

to complete tests such as finding visual targets and marking the mid-point of a line. However, its effect on their ability to carry out

a meaningful everyday task or to live independently was not clear. Patients with neglect should continue to receive general stroke

rehabilitation services but better quality research is needed to identify optimal treatments.

B A C K G R O U N D

Stroke can affect cognitive as well as physical and sensory abili-

ties (Wade 1985). Cognitive deficits include a disorder of spatial

awareness known as unilateral spatial neglect. The most widely

quoted definition of neglect is a description of the resulting be-

havioural disabilities: fails to report, respond, or orient to novelor meaningful stimuli presented to the side opposite a brain le-

sion (Heilman 1993). This definition does not describe the causal

mechanism of neglect but indicates that it is not simply due to

sensory or motor defects. Neglect is a disorder which can reduce a

persons ability to look, listen or makemovementstowardsone half

of their environment. This can also affect their ability to carry out

many everyday tasks, such as eating, reading and getting dressed

(Katz 1999). Stroke may differentially affect our ability to direct

our attention in thevisual,auditory or tactile modalities.Since dif-

ferent types of neglect can occur, several terms are used in clinical

practice, such as visual neglect, motor neglect, hemineglect, and

inattention (Bailey 1999). Although people do sometimes neglect

their ipsilesional (same) side, most researchers and clinicians focus

on the far more common neglect of contralesional space.

The reported incidence of neglect in stroke patients has varied

from as high as 90% (Massironi 1988) to as low as 8% (Sunder-

land 1987). The figures depend on the operational definition, se-

lection criteria for patients and method of assessment employed

(Bailey 1999; Bowen 1999; Ferro 1999). A previous systematic

review found that, in 16 of the 17 studies making the comparison,

contralesional neglect occurred more often after right than left

hemisphere stroke (Bowen 1999). Cognitive dysfunction, such as

neglect, can determine the outcome of rehabilitation by adversely

affecting mobility, discharge destination, length of hospital stay,

meal preparation and independence in self-care skills (Barer 1990;

Bernspang 1987; Neistadt 1993). In the light of these functionalimplications, it is not surprising that the rehabilitation of neglect

is an important aim in stroke rehabilitation.

Several investigators (Calvanio 1993; Gianutsos 1991; Robertson

1990) have reviewed interventions that have been designed specif-

ically to improve cognitive functioning following stroke and other

forms of neurological damage. They concluded that there is now

growing evidence that such interventions may produce a benefi-

cial effect across a variety of cognitive deficits. Cognitive rehabil-

itation includes training procedure(s) to improve cognitive func-

tions such as perception, memory and attention (Berrol 1990;

Levin 1990). These procedures sometimes aim to reduce the level

of impairment. Within rehabilitation there is a conceptual dis-

tinction between the effects a disease may have at different levels

(WHO 2001): impairment, activity (disability) and participation

(handicap). Therapists provision of aids and environmental adap-

tations aim to help the person adapt to their impairment rather

than change the underlying impairment itself. Other cognitive re-

habilitation approaches have been aimed at the level of activity

(disability). Loverro et al repositioned stroke patients beds with

the aim that improvements in spatial awareness would lead to less

disability as measured on the Barthel Index (Loverro 1988).

Most reports of the effectiveness of rehabilitation techniques have

been based on single case experimental designs rather than ran-

domised controlled trials (RCTs) (Lincoln 1995). Neglect reha-

bilitation is probably the cognitive area in which most RCTs have

been conducted and contains some of the oldest rehabilitationRCTs (Weinberg 1977). Some trials have shown positive results of

their efficacy although generalisation of training to untrained sit-

uations is rarely examined, nor is the maintenance of any immedi-

ate benefits. Thus, it is currently difficult to draw definite conclu-

sions regarding whether or not stroke patients benefit from neglect

rehabilitation or whether such impairment specific rehabilitation

facilitates independence in activities of daily living (ADLs). This

review aimed to systematically consider the evidence from RCTs

on the effectiveness of cognitive rehabilitation specifically aimed at

spatial neglect. It is not a review of whether the subgroup of stroke

patients with neglect benefit from general rehabilitation such as

physiotherapy or occupational therapy. Whatever the findings of

this review of cognitive rehabilitation specifically for neglect it is

essential that patients with neglect are included in general stroke

rehabilitation services.

O B J E C T I V E S

To assess whether cognitive rehabilitation improves functional in-




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dependence, performance on conventional and behavioural tests

of neglect, and destination on discharge in stroke patients with

neglect; to determine which types of interventions are effective;

and whether cognitive rehabilitation is more effective than stan-

dard care or an attention control.

C R I T E R I A F O R C O N S I D E R I N G

S T U D I E S F O R T H I S R E V I E W

Types of studies

In the first version of this review we sought all controlled trials

in which cognitive rehabilitation was compared to a control treat-

ment. In addition to well designed randomised controlled trials

(RCTs), other trials (suchas those describedas quasi-random)were

considered for inclusion but, if selected, were assigned a lower

methodological quality score. However, in this updated version

of the review we excluded all non-randomised trials to reduce se-

lection bias. These are listed in the Characteristics of excludedstudies table.

Types of participants

This review was confined to trials which included patients with

neglect following stroke. Stroke was confirmed by neurological

examination or computerised tomography (CT) scan, or both,

and neglect by neuropsychological examination. Thus, trials that

included participantswhose deficits werethe result of headtrauma,

brain tumour or any other brain damage were excluded unless a

subgroup of stroke patients could be identified for which there

were separate results or more than 75% of patients in the sample

were stroke patients. We excluded trials of patients with general

perceptual problems unless a subgroup of patients with neglect

could be identified.

Types of intervention

To be included in the review, a clinical trial had to report a com-

parison between an active treatment group that received one of

various cognitive rehabilitation programmes for neglect versus a

control group that received either an alternative form of treatment

or none. Cognitive rehabilitation was broadly defined to include

therapy activities designedto directlyreduce the level of the neglect

impairment or the resulting disability. Drug treatments were not

included. Cognitive rehabilitation could include structured ther-

apy sessions, computerised therapy, prescription of aids and mod-

ification of the patients environment as long as these were specific

to neglect. Theaim wasto directly targetthe neglect ratherthan toexamine whether patients with neglect happened to benefit from

general rehabilitation services. This is an important distinction.

When planning this updated version of the review, we became

aware that authors were categorising their neglect interventions

as either bottom-up or top-down processing (Parton 2004). Top-

down approaches aim to train the patient to voluntarily compen-

sate for their neglect and require awareness of the disorder. Meth-

ods include training in scanning and usually provide feedback

(Pizzamiglio 2004). Top-down approaches focus at the level of

disability rather than impairment. Bottom-up approaches do not

require awareness of the disorder. They aim to modify underlying

factors, that is to alter the impaired representation of space. Prism

adaptation is the mostpopular and recent example of a bottom-upapproach (Rossetti 1998). We included both approaches in this

updated review.

Types of outcome measures

Primary outcome

(1) Ratings on measures of functional disability: activities of daily

living (ADL) scales: Barthel Index (BI), Functional Independence

Measure (FIM), Frenchay Activities Index (FAI), or neglectspecific

ADL measures.

Secondary outcomes

(1) Performance on standardised neglect assessments: target can-

cellation (single letter, double letter, line, shape), line bisection.

Cancellation studies reporting number correct wereanalysed sepa-rately from those reporting number of errors. In addition to a con-

ventional subtest score (suchas letter cancellation) the behavioural

summary score from the Behavioural Inattention Test (BIT) was

used when available. In this updated review we removed outcomes

of attention and drawing tests to reduce the number of outcomes

being reviewed and to concentrate on those most relevant to ne-

glect.

(2) Discharge destination: whether a person was discharged to

live in their own home or to a care facility was included where

available, with deaths before discharge treated as not discharged

to their own home.

We did not specify a primary outcome in the first version of thisreview. In thisupdate,we decided thatthe primary outcomeshould

be the persistence of functional recovery, that is ADL benefits that

are maintained beyond the end of the intervention.

S E A R C H M E T H O D S F O R

I D E N T I F I C A T I O N O F S T U D I E S

See: Cochrane Stroke Group methods used in reviews.

(1) We searched the Cochrane Stroke Group Trials Register,

which was last searched by the Review Group Co-ordinator on

4 July 2005. In addition, we searched the following electronic

databases: MEDLINE (1998 to July 2005), EMBASE (1998 toJuly 2005), CINAHL (1998 to July 2005), PsycINFO (1998 to

July 2005) and the National Research Register (July 2005). The

following search strategies were used:

Database MEDLINE (Ovid)

1. exp cerebrovascular disorders/

2. (stroke$ or poststroke$ or cva$).tw.




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3. (cerebrovascular$ or cerebral vascular).tw.

4. ((cerebral or cerebellar or brainstem or vertebrobasilar) adj5

(infarct$ or isch?emi$ or thrombo$ or apoplexy or emboli$)).tw.

5. ((cerebral or intracerebral or intracranial or parenchymal

or brain or intraventricular or brainstem or cerebellar

or infratentorial or supratentorial or subarachnoid) adj

(haemorrhage or hemorrhage or haematoma or hematoma orbleeding or aneurysm)).tw.

6. 1 or 2 or 3 or 4 or 5

7. exp Perceptual disorders/

8. exp perception/

9. Attention/

10. Extinction (psychology)/

11. (hemineglect or hemi-neglect).tw.

12. ((unilateral or spatial) adj5 neglect).tw.

13. (perception or inattention or hemi-inattention or attention

or extinction).tw.

14. ((perceptual or visuo?spatial or visuo?perceptual or

attentional) adj5 (disorder$ or deficit$ or impairment$ or

abilit$)).tw.15. ((perceptual or visuo?spatial or visuo?perceptual or attention$

or cognit$ or scanning$) adj5 (training or re-training or

rehabilitation or intervention or therapy)).tw.

16. 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15

17. Randomized Controlled Trials/

18. random allocation/

19. Controlled Clinical Trials/

20. control groups/

21. clinical trials/

22. double-blind method/

23. single-blind method/

24. Placebos/

25. placebo effect/26. cross-over studies/

27. Research Design/

28. evaluation studies/

29. randomized controlled trial.pt.

30. controlled clinical trial.pt.

31. clinical trial.pt.

32. evaluation studies.pt.

33. random$.tw.

34. (controlled adj5 (trial$ or stud$)).tw.

35. (clinical$ adj5 trial$).tw.

36. ((control or treatment or experiment$ or intervention) adj5

(group$ or subject$ or patient$)).tw.

37. (quasi-random$ or quasi random$ or pseudo-random$ or

pseudo random$).tw.

38. ((control or experiment$ or conservative) adj5 (treatment or

therapy or procedure or manage$)).tw.

39. ((singl$ or doubl$ or tripl$ or trebl$) adj5 (blind$ or

mask$)).tw.

40. (coin adj5 (flip or flipped or toss$)).tw.

41. latin square.tw.

42. (cross-over or cross over or crossover).tw.

43. placebo$.tw.

44. sham.tw.

45. (assign$ or alternate or allocat$ or counterbalance$ or

multiple baseline).tw.

46. controls.tw.

47. or/17-4648. 6 and 16 and 47

Database EMBASE (Ovid)

1. exp cerebrovascular disease/

2. (stroke$ or cva$ or poststroke).tw.

3. (cerebrovasc$ or cerebral vascular).tw.






(haemorrhage or hemorrhage or haematoma or hematoma or

bleeding or aneurysm)).tw.6. 1 or 2 or 3 or 4 or 5

7. exp perception disorder/

8. exp perception/

9. exp attention/

10. visual deprivation/


12. ((unilateral or spatial or hemi?spatial) adj5 neglect).tw.


or extinction).tw.


attentional) adj5 (disorder$ or deficit$ or impairment$ or abilit$

or dysfunction)).tw.

15. ((perceptual or visuo?spatial or visuo?perceptual or attention$or cognit$ or scanning$) adj5 (training or retraining or


16. or/7-15

17. clinical trial/

18. randomized controlled trial/

19. controlled study/

20. double blind procedure/

21. single blind procedure/

22. randomization/

23. placebo/

24. prospective study/

25. types of study/

26. methodology/

27. comparative study/

28. parallel design/

29. crossover procedure/ or intermethod comparison/

30. clinical study/

31. random$.tw.

32. (controlled adj5 (trial$ or stud$)).tw.

33. (clinical$ adj5 trial$).tw.




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34. ((control or treatment or experiment$ or intervention) adj5

(group$ or subject$ or patient$)).tw.

35. (quasi-random$ or quasi random$ or pseudo-random$ or

pseudo random$).tw.

36. ((control or experiment$ or conservative) adj5 (treatment or

therapy or procedure or manage$)).tw.

37. ((singl$ or doubl$ or tripl$ or trebl$) adj5 (blind$ ormask$)).tw.

38. (coin adj5 (flip or flipped or toss$)).tw.

39. latin square.tw.

40. (cross-over or cross over or crossover).tw.

41. placebo$.tw.

42. sham.tw.

43. (assign$ or alternate or allocat$ or counterbalance$ or

multiple baseline).tw.

44. controls.tw.

45. or/17-44

46. 6 and 16 and 45

Database CINAHL (Ovid)1. exp cerebrovascular disorders/









bleeding or aneurysm)).tw.

6. 1 or 2 or 3 or 4 or 5

7. exp Perceptual disorders/

8. exp perception/9. Attention/




or extinction).tw.



abilit$)).tw.

14. ((perceptual or visuo?spatial or visuo?perceptual or attention$



15. or/7-14

16. random assignment/

17. random sample/

18. convenience sample/

19. Crossover design/

20. exp Clinical trials/

21. Comparative studies/

22. control (research)/

23. Control group/

24. Factorial design/

25. quasi-experimental studies/

26. Nonrandomized trials/

27. Placebos/

28. Community trials/ or Experimental studies/ or One-shot case

study/ or Pretest-posttest design/ or Solomon four-group design/

or Static group comparison/ or Study design/29. Research question/

30. Research methodology/

31. exp Evaluation research/

32. Evaluation/mt [Methods]

33. (clinical trial or systematic review).pt.

34. random$.tw.

35. ((singl$ or doubl$ or tripl$ or trebl$) adj25 (blind$ or

mask$)).tw.

36. (cross?over or placebo$ or control$ or factorial or sham?).tw.

37. ((clin$ or intervention$ or compar$ or experiment$ or

preventive or therapeutic) adj10 trial$).tw.

38. (counterbalance$ or multiple baseline$ or ABAB design$).tw.

39. or/16-3840. 6 and 15 and 39

Database PsycINFO (Ovid)

1. exp cerebrovascular disorders/









bleeding or aneurysm)).tw.6. 1 or 2 or 3 or 4 or 5

7. exp perceptual disturbances/

8. exp perception/

9. sensory neglect/

10. exp attention/

11. extinction (learning)/




or extinction).tw.



abilit$)).tw.

16. ((perceptual or visuo?spatial or visuo?perceptual or attention$



17. or/7-16

18. 6 and 17

19. (random$ or quasi-random$ or control$ or trial$ or blind$

or cross?over or experiment$ or compar$ or prospective).tw.




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20. 18 and 19

(2) For the purpose of this and other reviews (Lincoln 2001;

Majid 2001), trials in four areas of stroke rehabilitation

(cognitive rehabilitation, occupational therapy, speech

therapy, and treatment for mood disorders) were searched

for simultaneously using on-line computerised bibliographicdatabases: MEDLINE (1966 to 1998), BIDS EMBASE (1980 to

1998), CINAHL (1983 to 1998), PSYCLIT (1974 to 1998) and

CLINPSYCH (1980 to November 1994). These computerised

searches were conducted using combinations of the following

descriptors/key words: stroke/cerebrovascular accidents/

neurological disability and randomised controlled/clinical trials/

random allocation/double blind method and rehabilitation/

remedial therapy/treatment/intervention and cognitive/unilateral

neglect/visuospatial/visuoperceptual/memory/attention span/

concentration/hemianopia/attentional deficits/activities of daily

living/occupational therapy/leisure/dressing/self-care/domiciliary

rehabilitation.

(3) To ensure that trials not listed in the above databases werenot overlooked, in 1999 we handsearched all volumes of the

following journals.

American Journal of Occupational Therapy(1947 to 1998)

Aphasiology(1987 to 1998)

Australian Occupational Therapy Journal(1965 to 1998)

British Journal of Occupational Therapy(1950 to 1998)

British Journal of Therapy and Rehabilitation(1994 to 1998)

Canadian Journal of Occupational Therapy(1970 to 1998)

Clinical Rehabilitation(1987 to 1998)

Disability Rehabilitation(1992 to 1998), formerlyInternationalDisability Studies(1987 to 1991), formerlyInternationalRehabilitation Medicine(1979 to 1986)

International Journal of Language & CommunicationDisorders(1998), formerlyEuropean Journal of Disorders ofCommunication(1985 to 1997), formerlyBritish Journal ofDisorders of Communication(1977 to 1984)

Journal of Clinical Psychology in Medical Settings(1994 to1998), formerlyJournal of Clinical Psychology(1944 to 1994)

Journal of Developmental and Physical Disabilities(1992 to1998), formerlyJournal of the Multihandicapped Person(1989to 1991)

Journal of Rehabilitation(1963 to 1998)

International Journal of Rehabilitation Research(1977 to 1998)

Journal of Rehabilitation Science(1989 to 1996)

Neuropsychological Rehabilitation(1987 to 1998)

Neurorehabilitation(1991 to 1998)

Occupational Therapy International(1994 to 1998)

Physiotherapy Theory and Practice(1990 to 1998), formerlyPhysiotherapy Practice(1985 to 1989)

Physical Therapy(1988 to 1998)

Rehabilitation Psychology(1982 to 1998)

The Journal of Cognitive Rehabilitation (1988 to 1998),formerlyCognitive Rehabilitation(1983 to 1987)

The 1999 handsearch included a broad range of journals as it

covered trials in four areas of rehabilitation, only one of which

(neglect) was relevant to this specific review. Therefore for this

update we checked the Master List of journals that is searched

by The Cochrane Collaboration (http://www.cochrane.us/

masterlist.asp). We found that the journals relevant to neglect

had been handsearched. The resulting trials would be found

from the search of the Cochrane Central Register of Controlled

Trials (CENTRAL) carried out quarterly by the Cochrane Stroke

Group and we did not wish to duplicate effort.

(4) We screened reference lists of all relevant articles

(5) We used the three citation index databases, Science Citation

Index (SCI), Social Sciences Citation Index (SSCI) and Arts and

Humanities Citation Index (A&HCI) for citation tracking of

relevant included studies.

M E T H O D S O F T H E R E V I E W

As previously mentioned, the pre-1999 searching and selectionwas carried out simultaneously for four reviews, two of which have

been published in The Cochrane Library (Lincoln 2001; Majid2001).Updatedsearches specificto thispresent review werecarried

out in July 2005.

Two review authors (NBL, AB) independently selected trials to

be included in this review using the four inclusion criteria (types

of trials, participants, interventions and outcome measures). We

independently assessed the methodological quality of the trials,

with reference to theCochrane Handbook for Systematic Reviews ofInterventions(Higgins 2005), selected, entered, and cross-checkeddata for analysis. Differences were resolved by discussion.

Study characteristics and outcomeswere abstracted. The following

information was recorded: method of participant assignment,

adequacy of concealment, adequacy of matching at baseline,

description of intervention,sample size, numbers lostto follow up,

types of dependent variable(s), blinding at outcome assessment,

reported results and publication details. Where these data were

not available or unclear from the reports then they were sought

or confirmed by correspondence with the first author of the




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publication or both. Intention-to-treat analyses were used where

possible.

Where a crossover design was used (for example Schindler 2002)

only data from the first treatment period were used. Where initial

participants were randomised but later allocations were non-

randomised (for example Schindler 2002; Zeloni 2002) we onlyincluded thestudy if we could extract thedata on those randomised

(Zeloni 2002). If not we excluded the trial (Schindler 2002).

The left and right labels on the graphs were set according to the

method of scoring used on each outcome measure. For example,

a high score on the Barthel Index (BI) indicates a good outcome

and so the BI graph was set with the right label favouring the

experimental group. However, on the cancellation: number of

errors and line bisection outcomes a low score (that is fewer

errors) is better and so the left label of the graph was set to favour

the experimental group.

Activities of daily living (ADL) data, such as the BI, were treated as

continuous outcomes and mean and standard deviation data were

requested or calculated. We are aware that there is a difference

of opinion over how to deal with BI data. We have treated it

as an interval measurement whereas other people prefer to treat

it as ordinal. It is our view that, although from a theoretical

viewpoint there is an issue here, in practice it makes relatively

little difference. This is supported by a recent statistical study of

parametric versus nonparametric methods of BI data in stroke

trials, which recommended that means and standard deviations

(SDs) should be reported (Song 2005). Outcomes were analysed

as the standardised mean difference (SMD) and 95% confidence

intervals (CI). Random-effects models were used.

Odds ratios (OR) were selected for the outcome discharge

destination comparing the numbers discharged to their ownhome. Deaths before discharge were treated in this review as not

discharged to their own home. In this way those discharged home

were compared to everyone who was not discharged home.

Meta-analyses were conducted for studies of spatial neglect. To

reduce selection bias only those studies with adequate allocation

concealment were rated as A. A separate sensitivity analysis of

only the A-rated studies was conducted where there was more

than one A rated study.

The original analyses compared a rehabilitation approach with

any other control. The controls used were standard care, attention

control (wherethe control group were given extra hours of contact

in addition to their standard care to ensure the experimental and

control groups had similar amounts of contact or attention from

a therapist), and a control alternative neglect therapy. In this

update we kept the any control general comparison. However,

we added comparisons to separate out studies comparing two

equally feasible rehabilitation approaches (for example Edmans

2000; Robertson 2002) from those comparing one rehabilitation

approach with a control that was less likely to improve outcome

(for example Kalra 1997; Rossi 1990). This was done for the

primary outcome only, that is persisting functional or ADL data,

and was considered necessary as the different comparators answer

different rehabilitation questions.

In this update we also added a subgroup comparison by type of

intervention (grouped as bottom-up or top-down processing) toreduce the main limitation of the original review design, which

was that it was not set up to test which of several rehabilitation

approaches was effective. This subgroup analysis was for the

primary outcome only, that is persisting functional or ADL data.

D E S C R I P T I O N O F S T U D I E S

Data from 306 participants in 12 RCTs were included (Cherney

2002; Cottam 1987; Edmans 2000; Fanthome 1995; Kalra 1997;

Robertson 1990; Robertson 2002; Rossi 1990; Rusconi 2002;

Weinberg 1977; Wiart 1997; Zeloni 2002). Trials had small sam-

ple sizes. The smallest trials recruited and followed up four and

eight participants respectively (Cherney 2002; Zeloni 2002) andthe largest had a sample size of 50 (Kalra 1997). Statistical power

was rarely commented on, however some (such as Cherney 2002

and Kalra 1997) did explicitly state that they were intended as

pilot or feasibility studies.

All trials were of patients with neglect. In one trial (Rossi 1990)

someoftheparticipantsmayhavehadvisualsensorydeficits(visual

field or scanning) as well as or instead of neglect. There were 12

people with a visual sensory deficit in the experimental group and

15 in the control group. However, the review authors do not ex-

pect that their inclusion would bias theresults. Themajority of tri-

als only included patients with right hemisphere stroke (Cherney

2002; Cottam 1987; Fanthome 1995; Robertson 1990; Robertson

2002; Rusconi 2002; Weinberg 1977; Wiart 1997; Zeloni 2002).The others included those with either left or right hemisphere le-

sions, although in each trial there were more patients with right

hemisphere lesions.

Fiveof thecentres contributing the12 RCTs were based in theUK

(Edmans 2000; Fanthome 1995; Kalra 1997; Robertson 1990;

Robertson 2002), four were based in North America (Cherney

2002; Cottam 1987; Rossi 1990; Weinberg 1977), two in Italy

(Rusconi 2002; Zeloni 2002), and one in France (Wiart 1997).

Many trials recruitedfrom in-patient rehabilitation hospitals (such

as Cottam 1987; Rusconi 2002) or specialist in-patient stroke

services (for example Edmans 2000; Kalra 1997). As expected

in a stroke population, the average age of participants was over

60 years. Only one trial explicitly mentioned an age exclusion

criterion, that was aged over 80 years (Robertson 2002). Many

trials excluded participants on the basis of progressive dementia,

previous stroke, current cognitive or communication problems,

on the grounds that these would adversely affect responsiveness to

therapy. Occasionally the neglect data were extracted as part of a

larger study (Edmans 2000).




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A broad range of interventions was used (for full detailsseeChar-acteristics of included studies table). The included trials used both

top-down (Cherney 2002; Cottam 1987; Edmans 2000; Fan-

thome 1995; Robertson 2002; Rusconi 2002; Weinberg 1977;

Wiart 1997) and bottom-up (Kalra 1997; Robertson 1990; Rossi

1990; Zeloni 2002) approaches to rehabilitation. Several trials

provided equipment such as: fitting prisms to spectacles in orderto shift the image seen by the participant towards the neglected

side (Rossi 1990), or blinding the right side of goggles (Zeloni

2002), or specially adapted glasses which gave auditory feedback if

the participant failed to scan the neglected side (Fanthome 1995).

Wiart 1997 fitted participants with a vest with a metal pointer

attached. Robertson 2002 provided a limb activation device fit-

ted to the wrist, leg or shoulder.

Other interventions involved training with a therapist. For ex-

ample, various scanning tasks were used to demonstrate the pa-

tients deficit and show how a strategy could improve performance

(Cherney 2002). Another example of therapy-directed interven-

tion was spatio-motor cueing aimed at integrating attention and

limb movement (Kalra 1997). The principle behind this approach

is that movements of the affected limb in the neglected part of

space will result in improvements in attention skills and apprecia-

tion of spatial relationships on the affected side. Some approaches

involved multiple strategies, for example in the Wiart 1997 study

a therapist participated actively guiding and giving feedback while

the participant used the fitted pointer. A therapist was present in

both arms of the Rusconi 2002 trial but only provided cueing

and feedback in the experimental arm. This latter study is an

example of cognitive rehabilitation versus an attention control as

participants in both arms received equal amounts of time (that is

attention) from a therapist. What differed was the nature of the

therapy itself, that is whether or not cueing and feedback were

provided by the therapist.

The nature of the interventions was usually well described as were

the number, frequencyand durationof therapy sessions. The num-

ber of sessions varied from 12 (Robertson 2002) to 40 (Rusconi

2002) over a duration of 3 to 12 weeks. Sessions ranged from

daily to once a week and lasted from 30 to 75 minutes each. The

Rossi trial probably provided the highest dose of rehabilitation as

participants in the experimental arm wore their prisms during all

daytime activities for four weeks (Rossi 1990).

This updated review found that more trials included functional

outcome data, that is using measure of activities of daily living.

However few trials measured outcomes beyond the end of therapy

and so very few data existed on the persistence or maintenance offunctional recovery. This limited the comparisons that could be

made of onetypeof cognitive rehabilitation with anyother andthe

subgroup analyses of the top-down and bottom-up approaches.

In this updated review we only included the 12 trials that had

randomised participants. The search identified studies that were

published as randomised but the authors later confirmed thatnon-

random allocation had been used. These were then excluded. Ex-

amples of popular non-random methods were: allocating the first

set to one arm and the second to the other (Rossetti 1998; Tham

1997); alternate allocation (Pizzamiglio 2004), allocating by bed

number (Paolucci 1996), bed availability (Loverro 1988) or date

of admission (Harvey 2003). In total 22 studies were excluded.

The reasons for exclusion are detailed in the Characteristics ofexcluded studies table.

One further RCT of spatial neglect was identified and is awaiting

assessment anddata fromthe authors(Cubelli 1993). We are aware

of several ongoing RCTs which will be considered for inclusion in

the next update (Kerkhoff 2005; Rossetti 2005; Turton 2005).

M E T H O D O L O G I C A L Q U A L I T Y

Of the 12 included RCTs four did not provide further detail on

the randomisation method used (Cherney 2002; Cottam 1987;

Rossi 1990; Weinberg 1977) or the method of ensuring allocation

concealment. As they were published as RCTs we included them

but assigned a B rating meaning allocation concealment was un-

clear.

The other eight RCTs confirmed that they used external ran-

domisation (Kalra 1997; Robertson 1990), random number ta-

bles (Edmans 2000; Fanthome 1995; Wiart 1997), drawing pre-

labelled allocations from an envelope (Zeloni 2002) or, in the case

of Robertson 2002 and Rusconi 2002, the authors confirmed ran-

domisation but did not specify the method used. The methods

used by Kalra 1997 and Robertson 1990 provided a good guar-

antee of concealment of allocation and they were both given an

A rating. Edmans 2000 and Robertson 2002 were also given Aratings on the grounds that concealment was highly likely to have

been achieved, although it could not be guaranteed. For example,

in Edmans2000the researcher used random number tablesto pre-

paresequentially numbered opaque sealed envelopes. The random

number tables were then returned and due to the large number

randomised (80to thefull perception trial) it was unlikely that the

sequence would be remembered. The envelopes were only opened

in the presence of a witness. Robertson 2002 confirmed that the

recruiters were unaware of and unable to predict allocation con-

cealment. The other four trials (Fanthome 1995; Rusconi 2002;

Wiart 1997; Zeloni 2002) were rated as B as the information on

allocation concealment was unclear. For example, the combina-

tion of a small sample size with no external randomisation meantthat there was a potential risk to concealment (Fanthome 1995).

Edmans 2000, Fanthome 1995, Kalra 1997, Robertson 1990,

Robertson 2002, Rusconi 2002 and Zeloni 2002 used blinded

outcome assessors. Cherney 2002, Cottam 1987, Weinberg 1977

and Wiart 1997 provided no information suggesting that blinding

was used. Rossi 1990 did not use blinded outcome assessors.




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In summary there were four A rated trials, that is with adequate

allocation concealment (Edmans 2000; Kalra 1997; Robertson

1990; Robertson 2002). Blinded assessment was reported in seven

trials (Edmans 2000; Fanthome 1995; Kalra 1997; Robertson

1990; Robertson 2002; Rusconi 2002; Zeloni 2002).

R E S U L T S

Outcome data were available on 306 participants from 12 trials.

A large number of outcome measures were reported within single

studies, especially using standardised neglect tests, but not all par-

ticipantscompleted all outcomes. At times the number of outcome

measures used within a trial limited the analyses (for example,seecancellation below). With the exception of discharge destination

for which we used an odds ratio all other results refer to standard-

ised mean difference (SMD) and 95% confidence intervals (CI)

using random-effects models. The comparison numbers referred

toin this section (for example 01.01) refer tothe numberedgraphs.

Ratings on measures of functional disability: activities of dailyliving (ADL) scales: Barthel Index (BI) at discharge, Functional

Independence Measure (FIM)

Immediate

Six studies (206 participants) included a measure of disability im-

mediately after the end of rehabilitation or on discharge, five with

the BI (Edmans 2000; Kalra 1997; Robertson 2002; Rossi 1990;

Rusconi 2002) and one with the FIM (Wiart 1997). A seventh

(Robertson 1990) collected similar disability data on the Frenchay

Activities Index but these data were not available for the review. As

shown in the graph for comparison 01.01, the individual results

of two of these studies (rated A and B respectively for adequacy of

allocation concealment) favoured the experimental group (Kalra

1997; Wiart 1997). None favoured the control group. However,the overall effect for the six studies measuring immediate effect

on disability was small, with a wide confidence interval that in-

cluded zero and was not statistically significant, SMD 0.26 (95%

CI -0.16 to 0.67), P = 0.23.

Persisting

The primary outcome for this review was whether effects on dis-

ability persistedover time. Only twostudies, rated A andB respec-

tively, examined this (Robertson 2002; Wiart 1997). Outcome on

the FIM favoured the experimental group SMD 1.17 (95% CI

0.25 to 2.08), P = 0.01, which received one hour of specialised

neglect therapy for 20 days (Wiart 1997). However, the groups

were not well matched. The experimental group was younger and

had a higher baseline FIM score (66) than the control group (54).Outcome on the BI favoured neither group (Robertson 2002). As

shown in the graph for comparison 02.01 there is no overall evi-

dence for a persisting effect on ADL functioning from these two

studies 0.61 (95% CI -0.42 to 1.63), P = 0.24.

The same two studies were the only data available for comparison

03.01, persisting effects on ADL of one type of cognitive reha-

bilitation versus standard care or attention control. There are no

studies of comparison 04.01 persisting effects on ADL of one type

of cognitive rehabilitation versus another type.

The paucity of good functional data also restricted the planned

subgroup analyses of the persisting benefits of two rehabilitation

approaches, top-down and bottom-up. Comparison 06.01 is re-stricted to the single B-rated top-down study by Wiart 1997, the

results which favoured the experimental group are described pre-

viously. The effects of the bottom-up approach are shown in com-

parison 05.01. This A-rated study (Robertson 2002) did not find

evidence to support or refute bottom-up approaches SMD 0.12

(95% CI -0.62 to 0.86), P = 0.75.

Sensitivity analyses

Sensitivity analyses (A-rated studies only) of the ADL outcome,

conducted on threestudies of immediate effect on theBI (Edmans

2000; Kalra 1997; Robertson 2002) resulted in a reduced effect

size and wider confidence interval SMD 0.16 (95% CI -0.36 to

0.68) but did not alter the overall result of no significant effect,

P = 0.54. Sensitivity analysis of a persisting effect could not bereliably determined as there was only one small study (Robertson

2002).

Performance on standardised neglect assessments

Immediate

Almost all of the studies (11) provided data on standardised tests

of neglect, although there was no one measure common to all and

some studies used more than one measure. There was evidence

that cognitive rehabilitation improved immediate performance al-

though this varied depending on the test used, as described in de-

tail below. In summary, outcome favoured the experimental group

on: oneof the four cancellationtargetsthatwerescored fornumber

correct (double letter), cancellation scored for number of errors,

andline bisection. There was no evidencein favourof eithergroupon single letter, line or shape cancellation targets (although only

one study used the latter two outcomes) or the BIT behavioural

subtest score (three studies).

The number of targets correctly cancelled was measured using

four types of targets (comparison 01.02): single letter, double

letter, line and shape. Analysis beyond the subgroup level was

not valid asthreestudiesusedmorethanone type of target (Fan-

thome 1995; Weinberg 1977; Zeloni 2002). Subgroup analysis

by target type suggested that outcomes for one of these targets

favoured the experimental group: double letter SMD 1.8 (95%

CI 0.85 to 2.76), P = 0.0002. However, this was based on data

from only 25 participants in a single B-rated study (Weinberg

1977). Single letter cancellation was the most frequently used

cancellation measure (Edmans 2000; Fanthome 1995; Kalra

1997; Rusconi 2002; Weinberg 1977; Zeloni 2002). With the

exception of Edmans 2000 (an A-rated study which favoured

the control group) the other five studies all favoured the ex-

perimental group, although many of the confidence intervals

included zero and only Kalra 1997 was A rated. The overall




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subgroup effect for single letter cancellation was small and not

significant SMD 0.39 (95% CI -0.13 to 0.92), P = 0.14. Sensi-

tivity analyses conducted on the two A-rated studies (Edmans

2000; Kalra 1997) suggested a smaller effect and remained non-

significant SMD 0.01 (95% CI -0.84 to 0.86], P = 0.98 (com-

parison 01.08). Line (SMD 0.56, 95% CI -0.15 to 1.26, P =

0.12) and shape (SMD 0.09, 95% CI -0.69 to 0.88, P = 0.81)cancellation data were provided by two B-rated studies (Fan-

thome 1995; Zeloni 2002). Neither were significant.

Four studies using the number of errors made cancelling tar-

gets (Cottam 1987; Robertson 1990; Rossi 1990; Wiart 1997)

reported a small effect favouring the experimental group which

was of borderline statistical significance, SMD -0.65 (95% CI

-1.28 to -0.01), P = 0.05. These were based on 103 participants

and shown in the graph depicting comparison 01.03. Only one

(Robertson 1990) was A rated.

Four studies (89 participants) reporting line bisection perfor-

mance (Rossi 1990; Rusconi 2002; Wiart 1997; Zeloni 2002)

suggested a favourable outcome for the experimental groupSMD-0.84 (95% CI -1.36 to -0.33), P = 0.001. However, none

of these studies, shown in comparison 01.04, were A rated.

There was no evidence of an overall effect on the three stud-

ies using the BIT behavioural summary score (Cherney 2002;

Fanthome 1995; Robertson 1990) SMD -0.27 (95% CI -0.84

to 0.3), P = 0.35. As the graph for comparison 01.05 shows,

none of the individual studies showed an effect favouring the

experimental group. Only one study was A rated (Robertson

1990).

Persisting

The data available on whether beneficial effects on neglect assess-

ments persisted at follow up were limited to four studies (Cot-tam 1987; Fanthome 1995; Robertson 1990; Wiart 1997), only

one of which was A rated (Robertson 1990). There were no long-

term studies of number of targets correctly cancelled, comparison

02.02. Analyses were possible on: cancellation errors (02.03), line

bisection (02.04)and the BITbehavioural summary score (02.05).

The detailed results are as follows.

Three studies provided data on 52 participants on the can-

cellation number of errors outcome (Cottam 1987; Robertson

1990; Wiart 1997). A persisting effect favouring the experi-

mental group was found SMD -0.76 (95% CI -1.39 to -0.13),

P = 0.02.

Only Wiart 1997 provided data on persisting effects on line bi-section but these favoured the experimental group, SMD -1.09

(95% CI -2.0 to -0.18), P = 0.02.

Two studies (Fanthome 1995; Robertson 1990) of 31 partici-

pants did not find a persisting effect favouring the experimental

group on the BIT behavioural summary summary score, SMD

0.06 (95% CI -0.66 to 0.78], P = 0.87.

Sensitivity analyses

Sensitivity analyses of only the A-rated studies could only be con-

ducted in the one outcome area that contained more than one A-

rated study (comparison 01.08). The results are described above.

Discharge destination (comparison 01.06)

The information regarding whether a person was discharged tolive in their own home or to a care facility, was included if avail-

able. One RCT, rated A, investigated discharge destination as an

outcome (Kalra 1997). The odds of being discharged home had

a confidence interval that included one and were not significantly

higher for the experimental group OR 1.4 (95% CI 0.45 to 4.35),

P = 0.56.

Statistical heterogeneity

The variability among studies was found to be higher than ex-

pected by chance in a few of the outcome areas. The I-squared

test suggested substantial heterogeneity (greater than 50%) for

the primary outcome persisting effects on functional disability

and when taken immediately after intervention. The other area

with substantial heterogeneity was the immediate post-interven-

tion cancellation test (when scored as number of errors and sin-

gle letter cancelled correctly) although the heterogeneity on the

persisting effectsof number of errors wasonly 13% (nopersisting

data on correct). We used SMD and random-effects meta-analy-

sis. As discussed in theCochrane Handbook for Systematic Reviewsof Interventions(Higgins 2005), random-effects analysis incorpo-rates heterogeneity among trials although it is not a substitute for

thorough investigation. Given the small number of studies and

the small sample sizes in this review further investigation would

be of questionable value and was not carried out.

D I S C U S S I O N

In this updated review we excluded several previously included

non-randomised trials to reduce bias. We added several new, or

newly found, randomised controlled trials resulting in a review of

306participants from12 RCTs. We alsore-examinedthe quality of

the allocation concealment and re-gradedseveraltrials, resulting in

only four A-rated trials. The method of randomisation was gener-

ally poorly described and the published papers were often not suf-

ficiently methodologically detailed to determine whether conceal-

ment of group allocation or outcome assessor blinding was likely.

Both included and excluded trial authors were extremely helpful

in providing unpublished data. Therefore this review presents a

considerable amount of unpublished data and previously unpub-

lished clarification of the methods used by the original authors.

In contrast to the problems of methodological reporting, the re-

porting quality of the rehabilitation approach used has generally

improved. We also added comparisons to examine the two main

theoretical approaches to cognitive rehabilitation, bottom up and

top down.




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We found that outcome, following cognitive rehabilitation,

favoured the experimental group on several measures including

functional disability. Howeverthe effect sizesin these samples were

small and statistical analysis suggested they would not generalise

beyond the samples studied to the target population of people with

neglect after stroke. The results of sensitivity analyses of A-rated

studies that could be carried out supported the main analyses andsuggested an even smaller effect size and wider confidence inter-

vals. In contrast there was some generalisable evidence for both a

short-term and persisting effect on standardised neglect tests, such

as a reduction in errors cancelling targets and better line bisection

performance. However the validity of these measures (that is pa-

per-and-pencil tasks) is questionable. They may provide a useful

indication of changes in the underlying impairment but say little

of the persons ability to function in the complex everyday activ-

ities that are relevant to their life. Selection bias cannot be ruled

out in these studies with low quality concealment ratings, and in

fact the only A-rated study suggested a small effect favouring the

control group. Furthermore, the evidence for persisting effects is

restricted to three and one studies respectivelyfor cancellation andline bisection.

In conclusion, there is a growing number of cognitive rehabilita-

tion approaches that show promise on standardised neglect tests.

However, there is insufficient unbiased evidence to support or re-

fute the effectivenessof either bottom-up or top-down approaches.

Although there has been a steady rise in the number of neglect

rehabilitation trials we do not yet have sufficient high quality

RCTs with appropriate functional outcome measures with which

to make confident recommendations for clinical practice.

A U T H O R S C O N C L U S I O N S

Implications for practice

The effectiveness of cognitive rehabilitation strategies for reduc-

ing the disabling effects of neglect and increasing independence

remains unproven. No rehabilitation approach can at present be

supported or challenged by information from randomised trials.

Implications for research

There is sufficiently compelling evidence, from standardised ne-

glect tests, to encourage further trials of cognitive rehabilitation

for neglect. However, future studies need to improve on method-

ological and reporting issues and should define and distinguish

between different types of neglect. Key procedural aspects, such

as randomisation, concealment, completeness of follow up, and

blinding of assessors, must be sufficiently described. In fact the

process of random allocation appears to be misunderstood. Sev-

eral studies which described themselves as randomised were found

instead to use alternate allocation or other methods which risk

selection bias. Trialists are referred to the Cochrane Handbook for

Systematic Review of Interventions (Higgins 2005) for a descrip-

tion of acceptable methods of randomisation. Concealment and

blinding appear to be confused with each other but again are well

described in the Handbook (Higgins 2005). By its nature cog-

nitive rehabilitation is likely to be restricted to single blind trials

(of outcome assessors) as blinding of participants and therapists

is not realistic. Crossover trials are not appropriate for cognitiverehabilitation as the effects of one approach may well contaminate

the next, which invalidates long-term outcome measurements. As

rehabilitation aims to promote independence and maintenance of

effects it is not logical to expect thewashout effect that is possible

in some drug therapies.

Furthermore, trials need to have adequate statistical power to de-

tect a clinically meaningful difference. Power is very rarely men-

tioned in neglect trials and the small sample sizes used are unlikely

to be adequate. Sample specification and selection methods could

also be improvedon. Neglectis a heterogeneous condition andit is

unlikely that a single rehabilitation approach would be appropri-

ate for all types and severity and co-morbidity. Future trials should

provide adequate sample description, theoretical justification and

consider using stratified randomisation to avoid imbalance of any

factors likely to confoundthe trial. Future studies mustavoid using

non-random allocation methods (such as matching) to deal with

imbalance of known factors as this risks imbalance of potentially

important unknown factors by introducing selection bias.

There is scope for both pragmaticand explanatory RCTs. Explana-

tory trials provide evidence on efficacy, examining whether a single

rehabilitation approach (such as prism adaptation) can work in

an optimum situation (that is a more homogeneous sample with

little co-morbidity, treated by research therapists with protected

time in a controlled environment). There is also a need for prag-

matic RCTs to provide evidence on effectiveness and ideally costeffectiveness. Pragmatic trials examine whether rehabilitation does

workin a realisticclinical settingwith all of the pressuresthat places

on busy clinicians and examines the generalisability of findings

to the heterogeneous clinical populations likely to be referred for

rehabilitation. Finally completeness of follow up (and intention-

to-treat analysis) must be adequately conducted in future neglect

trials. Previous analyses tended to be per protocol and therefore

say little about the acceptability of rehabilitation to service users.

High drop out may well be an important measure of effectiveness

and future neglect trialists are recommended to consult the hand-

book (Higgins 2005) for a good discussion of intention to treat.

This reviewis ongoing andthe authors would begratefulto receive

information on ongoing trials for a future update.

P O T E N T I A L C O N F L I C T O F

I N T E R E S T

Nadina Lincoln has been involved in trials included in and ex-

cluded from this review (Edmans 2000; Fanthome 1995; Lincoln




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1985).

A C K N O W L E D G E M E N T S

We would like to thank the principal investigators of many of

the included and excluded trials who provided additional infor-mation to that published and to Clare Starmer for helping with

the searches. We are especially indebted to Brenda Thomas and

Hazel Fraser at the Cochrane Stroke Group for their continued

support and specialist guidance. Thanks also to the Editorial team

and external peer reviewer who provided useful suggestions for

improving the clarity and focus of this review. The initial searches

were funded by grants to Nadina Lincoln from The Stroke Asso-

ciation and the UK NHS Research and Development Programme

for Physical and Complex Disabilities. Michael Dewey provided

statistical input to the first published version of this review, for

which we are very grateful.

S O U R C E S O F S U P P O R T

External sources of support

The Stroke Association UK

NHS Executive Research and Development Programme Phys-

ical and Complex Disabilities UK

Internal sources of support

No sources of support supplied

R E F E R E N C E S

References to studies included in this review

Cherney 2002 {published data only}

Cherney LR, Halper AS, Papachronis D. Two approaches to treating

unilateral neglect after right hemisphere stroke: a preliminary inves-

tigation.Topics in Stroke Rehabilitation2003;9(4):2233.

Cottam 1987 {published data only}

Cottam GL.Visual scanning training for right hemispheric stroke pa-

tients exhibiting hemispatial neglect [Dissertation]. Mississippi: Uni-

versity of Mississippi, 1987.

Edmans 2000 {published and unpublished data}

EdmansJA, Webster J,Lincoln NB. A comparison of twoapproachesin the treatment of perceptual problems after stroke. Clinical Reha-

bilitation2000;14(3):23043.

Fanthome 1995 {published and unpublished data}

Fanthome Y, Lincoln N, Drummond A, Walker M. The treatment

of visual neglect using feedback of eye movements: a pilot study.

Disability Rehabilitation1995;17(8):4137.

Kalra 1997 {published and unpublished data}

Kalra L, Perez I, Gupta S, Whittink M. Effects of visual neglect

on stroke rehabilitation [Abstract]. Proceedings of the Challenge of

Stroke. The Lancet Conference. 15-16 October 1998; Vol. 71 [Abst

92].

Kalra L, Perez I, Gupta S, Wittink M. The influence of visual

neglect on stroke rehabilitation.Stroke1997;28(7):138691.

Robertson 1990 {published and unpublished data}

Robertson I, Gray J, Pentland B, Waite L. Microcomputer-based re-

habilitation for unilateral left visual neglect: a randomised controlled

trial.Archives of Physical Medicine and Rehabilitation1990;71:6638.

Robertson 2002 {published data only}Robertson IH, McMillan TM, MacLeod E, Edgeworth J, Brock D.

Rehabilitation by limb activation training reduces left-sided motor

impairment in unilateral neglect patients: a single-blind randomised

control trial.Neuropsychological Rehabilitation2002;12(5):43954.

Rossi 1990 {published data only}

Rossi P, Kheyfets S, Reding M. Fresnel prisms improve visual percep-

tion in stroke patients with homonymous hemianopia or unilateral




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visual neglect.Neurology1990;40:15979.

Rusconi 2002 {published data only}

Rusconi ML, Meinecke C, Sbrissa P, Bernardini B. Different cog-

nitive trainings in the rehabilitation of visuo-spatial neglect.Europa

Medicophysica2002;38:15966.

Weinberg 1977 {published data only}

Weinberg J, Diller L, Gordon W, Gerstman L, Lieberman A, Lakin

P, et al. Visual scanning training effect on reading-related tasks in

acquired right brain damage.Archives of Physical Medicine and Reha-

bilitation1977;58:47986.

Wiart 1997 {published and unpublished data}

Wiart L, Bon Saint ComeA, DebellaixX, PetitH, JosephPA, Mazaux

JM, et al. Unilateral neglect syndrome rehabilitation by trunk rota-

tion and scanning training. Archives of Physical Medicine and Reha-

bilitation1997;78:4249.

Zeloni 2002 {published data only}

Zeloni G, Farne A, Baccini M. Viewing less to see better. Journal of

Neurology Neurosurgery and Psychiatry2002;73:1958.

References to studies excluded from this review

Al Mahasneh 1991Al Mahasneh SM. Nursing interventions to reduce unilateral ne-

glect in right hemisphere stroke patients [Dissertation]. University

of Michigan 1991.

Beis 1999

Beis J-M, Andre JM, Baumgarten A, Challier B. Eye patching in

unilateral spatialneglect: efficacy of two methods.Archives of Physical

Medicine and Rehabilitation1999;80:716.

Butter 1992

Butter C, Kirsch N. Combined and separate effects of eye patching

and visual stimulation on unilateral neglect following stroke.Archives

of Physical Medicine and Rehabilitation1992;73:11339.

Carter 1980

Carter L, Caruso J, Languirand M, Berard M. Cognitive skill re-

mediation in stroke and non-stroke elderly.Clinical Neuropsychology

1980;2(3):10913.

Diller 1974

Diller L, Ben Yishay Y, Gerstman LJ, Goodki R, Gordon W, Wein-

berg J. Studies in cognition and rehabilitation in hemiplegia. Reha-

bilitation Monograph No. 50. New York: New York University, 1974.

Frassinetti 2002

Frassinetti A, Angeli V, Meneghello F, AvanziS, Ladavas E. Long-last-

ing amelioration of visuospatial negelct by prism adaptation.Brain

2002;125:60823.

Gordon 1985

Gordon W, Hibbard M, Egelko S, Diller L. Perceptual remediation

in patients with right brain damage: a comprehensive programme.

Archives of Physical Medicine and Rehabilitation1985;66:3539.

Harvey 2003

HarveyM, Hood B, NorthA, Robertson IH.The effects of visuomo-

tor feedback training on the recovery of hemispatial neglect symp-

toms: assessment of a 2-week and follow-up intervention.Neuropsy-

chologia2003;41:88693.

Klos 2005

Klos T. Personal communication 2005.

Lincoln 1985

Lincoln N, Whiting S, Cockburn J, Bhavnani G. An evaluation of

perceptual retraining.International Rehabilitation Medicine1985;7:

99110.

Loverro 1988

Loverro J, Reding M. Bed orientation and rehabilitation outcome

for patients with stroke hemianopsia or visual neglect. Journal of Neurologic Rehabilitation1988;2:14750.

Niemeier 1998

Niemeier JP. The Lighthouse Strategy: use of a visual imagery tech-

nique to treat visual inattention in stroke patients.Brain Injury1998;

12(5):399406.

Paolucci 1996

Antonucci G, Guariglia C, Judica A, Magnotti L, Paolucci S, Pizza-

miglio L, et al. Effectiveness of neglect rehabilitation in a randomised

group study. Journal of Clinical and Experimental Neuropsychology

1995;17(3):3839.

Paolucci S, Antonucci G, Guariglia C, Magnotti L, Pizzamiglio

L, Zoccolotti P. Facilitatory effect of neglect rehabilitation on the

recovery of left hemiplegic stroke patients: a cross-over study.Journal

of Neurology1996;243:30814.

Pizzamiglio 2004

Pizzamiglio L, Fasotti L, Jehkonen M, Antonucci G, Magnotti L,

Boelen D, et al. The use of opto-kinetic stimulation in rehabilitation

of the hemi-neglect disorder.Cortex2004;40:44150.

Rossetti 1998

Rossetti Y, Rode G, Pisella L, Farne A, Li L, Boisson D, et al. Prism

adaptation to a rightward optical deviation rehabilitates left hemis-

patial neglect.Nature1998;395(6698):1669.

Schindler 2002

SchindlerI, KerkhoffG, Karnath H-O,Keller I, Goldenberg G. Neck

muscle vibration induces lasting recovery in spatial neglect. Journalof Neurology Neurosurgery and Psychiatry2002;73:4129.

Tham 1997

Tham K, Tegner R. Video feedback in the rehabilitation of patients

with unilateral neglect.Archives of Physical Medicine and Rehabilita-

tion1997;78:4103.

Trudell 2003

Trudell C, Bodian L, Demaio JH, Cheskes BE, Reding M. Compar-

ison of hemi-field fresnel prisms versus patching for visual neglect

after stroke [Abstract]. Archives of Physical Medicine and Rehabili-

tation. 2003; Vol. 84:A9.

Webster 2001

Webster JS, McFarland PT, Rapport LJ, Morrill B, Roades LA,

Abadee PS. Computer-assisted training for improving wheelchairmobility in unilateral negelct patients. Archives of Physical Medicine

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P, et al. Training sensory awareness and spatial organisation in people

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Weinberg 1982

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organisation deficits in nonneglecting RBD stroke patients. Journal

of Clinical Neuropsychology1982;4(1):5975.

Young 1983

Young G, Collins D, Hren M. Effect of pairing scanning training

with block designtraining in the remediation of perceptual problemsin left hemiplegics. Journal of Clinical Neuropsychology 1983;5(3):

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References to studies awaiting assessment

Cubelli 1993

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spaziale unilaterale: verifica sperimentale della sua efficacia.Europa

Medicophysica1993;29:11121.

References to ongoing studies

Kerkhoff 2005

Kerkhoff G. Personal communication 2005.

Rossetti 2005

Rossetti Y. Personal communication 2005.

Turton 2005

Turton A. Personal communication 2005.

Additional references

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74:2132.

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ceptual impairments in acute stroke patients: effects on self-care abil-

ity.Stroke1987;18:10816.

Berrol 1990

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1990;47:21920.

Bowen 1999

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reported rate of occurrence of unilateral spatial neglect following

stroke.Stroke1999;30(6):1196202.

Calvanio 1993

Calvanio R, Levine D, Petrone P. Elements of cognitiverehabilitation

after right hemisphere stroke. BehaviouralNeurology1993;11(1):25

57.Ferro 1999

Ferro JM, Mariano G, Madureira S. Recovery from aphasia and ne-

glect. Cerebrovascular Diseases1999;9(Suppl 5):622.

Gianutsos 1991

GianutsosR. Cognitiverehabilitation:a neuropsychological specialty

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Heilman 1993

Heilman KM, Watson RT, Valenstein E. Neglect and related disor-

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Higgins 2005

Higgins JPT, Green S (eds). Cochrane Handbook for Systematic

Reviews of Interventions 4.2.5 [updated May 2005]. The CochraneLibrary. Chichester, UK: John Wiley & Sons, Ltd, 2005.

Katz 1999

Katz N, Harman-Maier A, Ring HM, Soroker NR. Functional dis-

ability and rehabilitation outcome in right hemisphere damaged pa-

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Levin 1990

Levin HS.Cogntiverehabilitation - unprovedbut promising.Archives

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WHO 2001

World Health Organization.International Classification of Function-

ing, Disability and Health (ICF). Geneva: World Health Organiza-

tion, 2001.

Indicates the major publication for the study

T A B L E S

Characteristics of included studies

Study Cherney 2002

Methods RCT: no further information provided. No mention of blinded outcome assessments.

Quality of allocation concealment rated as B/C: unclear/inadequate.

Participants USA.

Four right hemisphere stroke patients with clinical evidence of neglect at least six months post onset.Exptl n = 2, cntrl n = 2.

Mean age (SD): exptl 69.5 yrs (23.3), cntrl 62.0 yrs (5.7).

Sex (m): exptl 2, cntrl 1.

Side of damage (RBD): exptl 2, cntrl 2.

Mean months post-onset

Bowen Neglect

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