Neuropsychological Rehabilitation

An International Journal

ISSN: 0960-2011 (Print) 1464-0694 (Online) Journal homepage: http://www.tandfonline.com/loi/pnrh20

Effects of intensive neuropsychological

rehabilitation for acquired brain injury

Meike Holleman, Martie Vink, Rinske Nijland & Ben Schmand

To cite this article: Meike Holleman, Martie Vink, Rinske Nijland & Ben Schmand (2016): Effects
of intensive neuropsychological rehabilitation for acquired brain injury, Neuropsychological
Rehabilitation, DOI: 10.1080/09602011.2016.1210013

To link to this article: http://dx.doi.org/10.1080/09602011.2016.1210013

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 NEUROPSYCHOLOGICAL REHABILITATION, 2016
http://dx.doi.org/10.1080/09602011.2016.1210013

Effects of intensive neuropsychological rehabilitation

for acquired brain injury
Meike Hollemana,b, Martie Vinka, Rinske Nijlanda and Ben Schmandc,d
a
Amsterdam Rehabilitation Research Centre, Reade, Amsterdam, The Netherlands; bDepartment of
Medical Psychology, Jeroen Bosch Hospital, ‘s-Hertogenbosch, The Netherlands; cDepartment of
Medical Psychology, Academic Medical Centre at the University of Amsterdam, Amsterdam, The
Netherlands; dProgrammagroep Brein en Cognitie, Faculty of Social and Behavioural Sciences,
University of Amsterdam, Amsterdam, The Netherlands
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ABSTRACT
The objective of the study was to examine the effects of a comprehensive
neuropsychological rehabilitation programme (Intensive NeuroRehabilitation, INR)
on the emotional and behavioural consequences of acquired brain injury (ABI). The
participants were 75 adult patients suffering from ABI (33 traumatic brain injury, 14
stroke, 10 tumour, 6 hypoxia, 12 other), all of whom were admitted to the INR
treatment programme. The main outcome measures were: general psychological
well-being (Symptom-Checklist-90), depression and anxiety (Beck Depression
Inventory-II, Hospital Anxiety and Depression Scale, State Trait Anxiety Inventory),
and quality of life (Quality of Life in Brain Injury). The study was a non-blinded,
waiting-list controlled trial. During the waiting-list period no or minimal care was
provided. Multivariate analysis of the main outcome measures showed large effect
sizes for psychological well-being (partial η 2 = .191, p < .001), depression (partial
η 2 = .168, p < .001), and anxiety (partial η 2 = .182, p < .001), and a moderate effect
size for quality of life (partial η 2 = .130, p = .001). Changes on neuropsychological
tests did not differ between the groups. It was concluded that the INR programme
improved general psychological well-being, depressive symptoms, anxiety, and
quality of life. The programme does not affect cognitive functioning.

ARTICLE HISTORY Received 4 April 2016; Accepted 1 July 2016

KEYWORDS Acquired brain injury; neuropsychological rehabilitation; holistic neuropsychological rehabilitation

Introduction
The consequences of acquired brain injury (ABI) are manifold, with cognitive and
emotional dysfunction, and behaviour changes persisting into the chronic phase. Neu-
ropsychological rehabilitation is concerned mainly with these “invisible” sequelae,
aiming to help survivors of acquired brain injury to minimise these consequences.
Also, neuropsychological rehabilitation can be focused on helping them deal with the

CONTACT Meike Holleman meikeholleman@outlook.com Amsterdam Rehabilitation Research Centre,

Reade, Amsterdam, The Netherlands; Department of Medical Psychology, Jeroen Bosch Hospital, Henri Dunant-
straat 1, 5223 GZ, ‘s-Hertogenbosch, The Netherlands
Supplemental data for this article can be accessed 10.1080/09602011.2016.1210013
© 2016 Informa UK Limited, trading as Taylor & Francis Group
 2 M. HOLLEMAN ET AL.

changes in ways that are constructive for optimal functioning in personal, interpersonal
and vocational domains.
In the acute phase, during which the largest part of spontaneous recovery takes
place, rehabilitation efforts are mostly directed at restoration of function. In contrast,
in later phases, treatment generally focuses on optimisation of function by means of
compensatory strategy training. This holds especially for cognitive functions and inter-
personal behaviour.
The primary consequences of brain injury often result in secondary changes that can
be detrimental to a person’s functioning. For example, insecurity resulting from cogni-
tive deficits and the ensuing experiences of failure may lead to avoidance and anxiety,
leading to increased disability in daily, social, and vocational functioning. Depression
and anxiety are common in brain injury survivors (Anson & Ponsford, 2006; Gould, Pons-
ford, Johnston, & Schönberger, 2011; Koponen et al., 2002). Neuropsychological rehabi-
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litation aims to treat both the primary and secondary consequences of brain injury by
improving cognitive skills and addressing emotional and behavioural problems.
Comprehensive or holistic neuropsychological rehabilitation offers group-based
treatment combined with individual therapy sessions in a therapeutic learning environ-
ment. Typically, these programmes focus on metacognitive aspects such as increasing
awareness of the individual’s cognitive, emotional, and interpersonal problems. It is
assumed that acceptance of these changes can only take place when the patient is
knowledgeable about his or her own individual injury-related difficulties. Similarly,
being aware of cognitive deficits is a prerequisite for the optimal use of compensatory
strategies, which are important tools to ease the burden of these deficits. A controlled
group therapy setting is believed to be the ideal method of learning about one’s
emotional and interpersonal or behavioural problems, as patients can mirror each
other’s behaviour and provide direct feedback. Comprehensive neuropsychological pro-
grammes aim at better community integration and enabling patients to lead a satisfac-
tory existence despite their limitations.
In their recent, updated review of evidence-based cognitive rehabilitation, Cicerone
et al. (2011) conclude that “comprehensive holistic neuropsychological rehabilitation
can improve community integration, functional independence, and productivity, even
for patients who are many years post-injury” (p. 526), leading to their recommendation
to provide post-acute, comprehensive holistic neuropsychological rehabilitation as a
“practice standard” for the reduction of cognitive and functional disability after moderate
or severe traumatic brain injury. However, this review also highlights the paucity of meth-
odologically sound (i.e., randomised, controlled) studies of these holistic programmes.
We conducted a non-blinded waiting-list controlled trial to evaluate the effects of
comprehensive holistic neuropsychological rehabilitation on general psychological
and emotional well-being and quality of life.

Methods
Participants
All patients enrolled in the Intensive NeuroRehabilitation (INR) programme at Reade,
centre for Rehabilitation and Rheumatology, Amsterdam, The Netherlands, between
January 2010 and January 2014 were included in the study. Seventy-five patients
were enrolled in the programme during this period.
 NEUROPSYCHOLOGICAL REHABILITATION 3

Patients referred to the programme were selected for enrolment by means of a semi-
structured interview with one or two neuropsychologists and a physiatrist. Enrolment
criteria were (1) having sustained brain injury of a non-progressive nature (e.g., trau-
matic brain injury, stroke, brain tumour, infection) at least 12 months previously, docu-
mented by medical/surgical records and/or brain imaging (e.g., CT or MRI scan);
(2) experiencing a combination of problems in social, behavioural, emotional, and/or
vocational functioning; (3) between 18 and 65 years of age; and (4) demonstrating
enough awareness of the psychosocial consequences of their brain injury to be intrin-
sically motivated for this intensive treatment programme.
Exclusion criteria were progressive neurological disease; severe language deficits
interfering with communication; severe behavioural disorders, e.g., aggression or
extreme disinhibition or impulsivity, interfering with functioning in a group; psychiatric
disorders; insufficient proficiency in the Dutch language; and substance abuse.
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Allocation
Thirty-three patients were included in the control group and 42 in the experimental
group. Allocation to either group depended on time of referral: patients referred a
minimum of three and a half months before the next programme was due to start,
were asked to participate in the control group. Patients referred closer to the scheduled
starting date of the treatment group they were to participate in were included in the
experimental group.
The two groups did not differ at baseline on age, sex, education, estimated premor-
bid IQ, type of injury, or time since injury (Table 1). The level of education was rated
according to the UNESCO International Standard Classification of Education (ISCED)
classification system (UNESCO Institute for Statistics, 1997).
The sample consisted predominantly of Caucasian men and women, with the excep-
tion of two Dutch male participants of Caribbean origin. Typically for the ABI population,
more men than women were included.
Injury type was heterogeneous. Traumatic brain injury was most common. The
“other” category consisted of diverse diagnoses, such as epilepsy surgery, cerebral
inflammation, and intoxication. Three of the patients in this category (one in the

Table 1. Demographic and clinical characteristics of the groups.

Experimental (N = 42) Control (N = 33) Sig.
Mean age (SD) (years) 43.3 (12.4) 40.7 (12.5) p = .38a
Sex 27 male 20 male p = .81b
64.3% male 60.6% male
Mean education (ISCED) (SD) 4.2 (1.1) 4.2 (1.1) p = .69c
Premorbid IQ (based on DART) (SD) 96.9 (14.8) 93.0 (12.3) p = .23a
Type of injury p = .95b
. TBI 18 15
. Stroke 9 5
. Tumour 6 4
. Hypoxia 3 3
. Other 6 6

Time since injury (years) 7.9 (6.4) 6.9 (8.9) p = .15c

Age at (first) injury (SD) (years) 35.4 (15.4) 33.8 (14.4) p = .66a
a
Student’s t; bChi-square; cMann-Whitney.
ISCED = International Standard Classification of Education; DART = Dutch Adult Reading Test.
 4 M. HOLLEMAN ET AL.

experimental, two in the control group) had sustained more than one brain injury, e.g.,
meningitis at a young age, and epilepsy for which they underwent surgery as an adult.
As can be expected, injury severity was also very heterogeneous. Severity indicators,
such as duration of coma or Glasgow Coma Scale score often were not available,
especially in the files of participants whose injury occurred many years previously. In
some cases, there had been no loss of consciousness (e.g., in the patients with brain
tumours). Injury severity was not included as a variable.
Level of disability varied greatly, as can be gathered from the pooled neuropsy-
chological results displayed in Table 2 (see also Measures section below), but did
not differ between the two groups. All patients lived more or less independently,
with some receiving care in the form of community-based support (e.g., help with
household and/or administrative tasks). Most patients were unemployed or on dis-
ability payment; a minority worked part-time, often in a sheltered or specialised
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setting.

Measures
The primary outcome measures were general psychological well-being, depression,
anxiety, and quality of life. All questionnaires used have adequate to good psychometric
properties.
Neuropsychological tests were used to describe the cognitive status of the sample.
Apart from retest or learning effects, no changes were expected in these tests, since
all subjects were neurologically plateaued.

Psychological well-being
Psychological well-being was measured using the Dutch version of the Symptom Check-
list-90 (SCL-90; Arrindell & Ettema, 2003; Derogatis, 1977). This 90-question scale covers
eight domains of psychopathology that are summed into an overall so-called “psycho-
neuroticism” score, reflecting the individual’s degree of psychological distress. This total
score is a global indicator of emotional well-being. Higher overall and subscale scores
indicate more psychopathology and greater distress. The SCL-90 is considered an excel-
lent instrument to evaluate treatment outcome (Arrindell & Ettema, 2003).

Depression and anxiety

The Beck Depression Inventory II (BDI-II; Beck, Steer, & Brown, 1996) was used to inves-
tigate symptoms of depression. The Dutch version of the Hospital Anxiety and
Depression Scale (HADS; Zigmond & Snaith, 1983) was used as an indicator of both
depression and anxiety. Anxiety disposition was investigated using the trait version of
the Zelf-Beoordelings Vragenlijst (ZBV; Van der Ploeg, Defares, & Spielberger, 1979),
which is a Dutch version of the Spielberger State-Trait Anxiety Inventory (STAI-form Y;
Spielberger, Gorsuch, Lushene, Vagg, & Jacobs, 1983).

Quality of life
Quality of life was investigated with a questionnaire aimed specifically at people suffer-
ing from brain injury: Quality of Life in Brain Injury (QOLIBRI; Von Steinbüchel, Petersen,
Bullinger, & the QOLIBRI Task Force, 2005). The QOLIBRI consists of two scales. The first
scale examines perceived satisfaction with different areas of life (ability to think; feelings
and self-image; independent functioning in daily life; social relationships). The second
 NEUROPSYCHOLOGICAL REHABILITATION 5

scale examines perceived burden (of emotions; of handicaps and problems; of physical
problems). Scores are converted to a 1–100 scale. Higher total scores represent better
global, health-related quality of life. Test-retest reliability and internal consistency are
good (rtt = .78–.85 and α = .75–.89, respectively), and remain so in patients with low cog-
nitive functioning (Von Steinbüchel et al., 2010).

Neuropsychological tests
Neuropsychological assessment consisted of domains and tests as described below.

Premorbid intelligence. Premorbid intelligence was estimated with the Dutch version
of the National Adult Reading Test (NART; Nelson & Willison, 1991): the Dutch Adult
Reading Test (DART; Nederlandse Leestest voor Volwassenen; Schmand, Lindeboom,
& van Harskamp, 1992).
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Attention and information processing speed. Trailmaking test part A (Reitan &
Wolfson, 1985), Stroop Color-Word test word reading and colour naming (Stroop,
1935), D2 attention test speed and concentration performance (Brickenkamp & Ooster-
veld, 2011), and the Wechsler Adult Intelligence Scale (WAIS-III; Wechsler, 1997, 2000)
processing speed index were included as measures of (sustained) attention and/or pro-
cessing speed.

Memory. Working memory was assessed using the WAIS-III working memory index
(Wechsler, 1997, 2000). Immediate and delayed recall of the Dutch version of the Rey
Auditory Verbal Learning Test (Saan & Deelman, 1986), and immediate and delayed
recall of the Logical Memory subtest from the Rivermead Behavioural Memory Test
battery (Van Balen & Groot Zwaaftink, 1993; Wilson, Cockburn, & Baddeley, 1989)
were used to assess verbal episodic memory.

Executive functioning. Measures of executive functioning included Category Fluency

(animal and occupation fluency; Groninger Intelligentie Test 2) (Luteijn & Van der
Ploeg, 1983), Trailmaking test part B relative to part A, and the Stroop Color-Word
test interference condition, corrected for colour naming.
All neuropsychological test data were converted into age, education, and sex-cor-
rected T-scores (Schmand, Houx, & de Koning, 2012) and subsequently pooled into
average z-scores for each of the three domains as described above.

Intervention
The Intensive NeuroRehabilitation programme (INR) is an outpatient group programme
for patients in the chronic phase of acquired brain injury. It aims at enhancing aware-
ness of and insight into the changes that have resulted from their brain injury, in
order for them to cope better with the cognitive, emotional, and behavioural conse-
quences. The programme focuses on acquiring compensatory strategies, adequate
coping skills, efficient interpersonal skills, and acceptance of the consequences of the
injury. The fixed composition of the groups and the daily structure provide a safe learn-
ing environment.
Subsequent to the first interview, candidates attend the programme as a guest for one
day, in order for them to become acquainted with the programme and for the staff to judge
 6 M. HOLLEMAN ET AL.

whether or not they seem able to benefit from, and work in, a similar group of patients. If in
the next interview both staff and candidate decide positively on participation, goals are set
for the patient to work on during the programme. Patients are strongly encouraged to
involve significant others, although this is not an inclusion criterion.
Programme length is 16 weeks, consisting of 2 x 7 weeks of training, separated by a
2-week break. Patients attend the programme on Monday through to Thursday with 5
hours of training each day, except on Wednesdays, when there is no afternoon sche-
dule. For the most part, therapy takes place in the group, which is fixed and consists
of eight patients.
A full programme day consists of five different sessions. The first session in the
morning, after a team meeting, is Orientation. In this session, that typically lasts 45
minutes to 1 hour, trainees set and review goals. On Monday, goals for the week are
set, and on Thursday, trainees set goals for the weekend. All goals are reviewed and
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evaluated daily in order for the trainees to become aware of their successes and of
the compensatory strategies that helped attain them. In this way, self-efficacy and con-
fidence are promoted. In addition, the Orientation session is chaired by one of the trai-
nees (assisted by one of the trainers), and, as such, functions as a practice place for
interpersonal and communication skills.
A one-hour psycho-education session, Cognitive Training, helps trainees become
better acquainted with the brain in general, and the possible dysfunctions after brain
injury, specifically. Written information and experiential exercises help trainees
become (more) aware of the characteristics of their own brain injury. Compensatory
strategies are discussed and practised.
The last morning session is Relaxation and Physical Activities, which focuses on aware-
ness of, and dealing with, fatigue and emotional and physical tension. A physical thera-
pist and a trainer lead this session. Activities range from relaxation techniques to
hydrotherapy, walking outside, and yoga exercises, to fitness and team sports.
After a lunch break, the afternoon sessions start with Interpersonal Training. In this
one-hour session, trainees hold presentations. Video recordings and feedback from
fellow trainees, trainers, and guests help trainees become aware of how they come
across and what might help them to communicate more effectively. Learning how to
give and receive feedback in a functional and constructive way is an important interper-
sonal and communication exercise.
In the final session, Group Discussion, a wide range of topics is presented and dis-
cussed, helping trainees work through issues and practice interpersonal skills (e.g.,
turn-taking, dealing with differences of opinion).
All sessions are led by two or three trainers (except for Relaxation and Physical Activi-
ties). Staff consists of four neuropsychologists and one psychological assistant (the trai-
ners), two physical therapists, one vocational therapist, a physiatrist, and a secretary.
Each trainee is assigned a personal coach (one of the trainers) for weekly individual
counselling sessions.
Apart from the group sessions, a family group meeting is organised every two weeks,
in which partners and other relatives discuss topics such as consequences of brain
injury, dealing with behavioural problems, or their own role in supporting the partici-
pants’ learning process.
In the 7th and the 14th week of the programme, each trainee holds a halfway or final
presentation for an audience consisting of their family and friends. In these presenta-
tions, the trainees inform their important others of the history and varying
 NEUROPSYCHOLOGICAL REHABILITATION 7

consequences of their brain injuries, their learning process during the programme and
their goals for either the next half of the programme or for the future.
Upon completion of the programme, goals are set for the near future. These goals are
evaluated and reviewed in a follow-up meeting, one month after the programme finishes.
At that occasion, new goals for a second follow-up meeting, two months after the first
one, are set. At the second follow-up meeting, the trainees set longer-term goals.
For an illustration of the types of patients, their goals, and strategies, see the case
vignettes provided in the Supplemental Data.

Procedures
All patients provided oral and written consent for the anonymous use of their psycho-
metric data. All measures used were part of the routine pre- and post-treatment assess-
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ment in the treatment programme. The waiting-list control group underwent an

additional (baseline) assessment, on average 15 weeks before the standard pre-
treatment assessment. Assessment took place at baseline (i.e., pre-treatment for the
experimental group and extra baseline for the control group) and at follow-up
(i.e., post-treatment for the experimental group and pre-treatment for the control
group). All control patients agreed to complete the extra set of questionnaires; two
declined the extra neuropsychological assessment.
Neuropsychological testing was done by one of the five trainers, all of whom have
extensive experience in neuropsychological assessment. Testing took place in a quiet
room and according to the standard instructions.
Participants completed the questionnaires at home or at the rehabilitation centre
after the assessment, according to their preference. Proxy questionnaires were given
to the participants to be passed on to the proxy of their selection, along with a
return envelope.

Data preparation and analysis

Missing values. Between 3.3% (baseline assessment) and 6.3% (follow-up) of the data
in the primary outcomes (self-report questionnaires) were missing. This was largely
due to the missing sets of questionnaires of six patients. In two patients, both
primary and secondary outcome data at post-treatment assessment were missing.
One patient missed the last three weeks of the programme due to family circum-
stances, and the second patient exited the programme after the half-way break
because she experienced the programme as too taxing, both physically and mentally.
Two other patients underwent neuropsychological assessment at follow-up but did
not complete the questionnaires at that time. One patient refused to undergo the
standard post-treatment neuropsychological assessment. In two other cases, baseline
measures (questionnaires and/or neuropsychological data) were missing. A few ques-
tionnaires had been left entirely blank and were not detected as such by the exami-
ners. More often, individual items were missing.
In the primary outcome measures, small amounts of single missing items were sub-
stituted by the participant’s average score on the remaining items of the (sub)scale.
When longer series of items (e.g., a whole page of a questionnaire) or entire instruments
were missing at either time point, the method of “last observation carried forward
(LOCF)/backward (LOCB)” was applied, i.e., the individual values were substituted by
the relevant values obtained at the other time point. In the neuropsychological test
 8 M. HOLLEMAN ET AL.

data, LOCF or LOCB was only applied in the cases of entire missing sets of data. Smaller
amounts of missing items were left blank.

Analyses. Student’s t-tests and non-parametric tests were used to compare group
characteristics and demographics at baseline. A one-way multivariate analysis of var-
iance (MANOVA) was conducted with the difference scores of the primary measures;
another one-way MANOVA was conducted with the difference scores on the neuropsy-
chological measures.
All analyses were performed using PASW, version 22.0 for Macintosh.

Primary outcome measures. At baseline and at follow-up, differences between the

groups on the primary outcome measures were tested using either Student’s t-tests
for normally distributed scores or non-parametric tests for non-normally distributed
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scores.
Baseline scores on the general psychological well-being measure (SCL-90 total score),
the depression measures (BDI-II total score and HADS Depression subscale), the anxiety
measures (ZBV total score, and HADS Anxiety subscale), and quality of life (QOLIBRI total
score) were transformed into z-scores for both groups combined. Means and standard
deviations at baseline were used to calculate z-scores at follow-up. The z-scores of the
depression measures were averaged to create a depression score. A similar measure was
created for anxiety by averaging the z-scores of the two anxiety measures. Difference
scores between baseline and follow-up were calculated for these pooled variables,
general psychological well-being, and the QOLIBRI score. The latter was subsequently
reversed (multiplied by −1), in order for increase and decrease to mean the same for
all four variables (decrease = improvement).
A multivariate analysis of variance was conducted with these difference scores as
dependent variables in order to test our main hypothesis.
We predicted that psychological distress (psychoneuroticism scores and self-reported
symptoms of depression and anxiety) would decrease in the experimental, but not in
the control group. Similarly, we expected to see an increase in self-reported quality of
life in the experimental group only.

Secondary (neuropsychological) measures. The secondary measures were analysed in

a similar way as the primary measures.
All neuropsychological test data were converted into z-scores, corrected for age and/
or education and/or sex depending on the population norms available.
For each of the three cognitive domains, a composite measure was created. WAIS-III
processing speed index, D2 total score minus errors, D2 concentration performance,
Trailmaking test part A, and Stroop Color-Word test word reading and colour naming
speed were averaged into the attention and processing speed measure. The memory
measure consisted of the averaged z-scores of the Auditory Verbal Learning Task
immediate and delayed recall, Rivermead Behavioural Memory Test (RBMT) stories
immediate recall and delayed recall, and the WAIS-III working memory index. The execu-
tive measure was the average z-score of the two semantic fluency tests (animals and
occupations), Trailmaking test part B, corrected for part A, and Stroop Color-Word
test interference condition, corrected for colour naming speed. A multivariate analysis
of variance was conducted with the difference scores between the first and second
measurements as dependent variables.
 NEUROPSYCHOLOGICAL REHABILITATION 9

Table 2. Means and standard deviations of raw scores on primary measures and z-scores and standard deviations
on neuropsychological measures for both groups at both assessments.
Baseline Follow-up
Measure Experimental Control Sig. (p) Experimental Control Sig. (p)
SCL-90 total 183.3 (52.5) 181.3 (55.3) .721* 153.7 (44.3) 185.5 (49.7) .005*
(Psychoneuroticism)
BDI-II 21.0 (9.9) 21.6 (7.4) .471* 14.7 (9.4) 22.2 (8.9) .001*
HADS
Depression 8.4 (4.4) 8.3 (4.4) .955 5.8 (4.2) 8.5 (4.4) .009*
Anxiety 9.1 (4.4) 8.8 (3.7) .771 6.4 (4.1) 9.4 (4.5) .003*
ZBV-trait 50.9 (11.6) 52.3 (11.2) .619* 41.9 (11.0) 51.2 (13.1) .002*
QOLIBRI
Satisfaction 41.7 (14.6) 44.0 (13.3) .306* 50.6 (18.3) 42.0 (15.4) .034
Burden 75.2 (14.0) 71.3 (13.5) .226 81.6 (13.4) 73.6 (12.4) .018*
Overall 58.4 (12.3) 57.6 (11.9) .773 66.1 (13.9) 57.8 (11.6) .008
Neuropsychological domains
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Attention & processing speed −1.0 (1.0) −0.7 (0.8) .104 −0.7 (1.0) −0.5 (0.9) .390
Memory −0.8 (0.9) −0.7 (0.9) .626 −0.6 (.9) −0.7 (1.0) .745
Executive function −0.3 (0.8) −0.1 (0.7) .460 −0.1 (.9) −0.2 (0.8) .672
SCL-90 = Symptom Checklist-90; BDI-II = Beck Depression Inventory-II; HADS = Hospital Anxiety & Depression
Scale; ZBV-trait = Zelfbeeldenvragenlijst-trait; QOLIBRI = Quality of Life in Brain Injury.
*indicates use of Mann-Whitney tests because of non-normality; figures in bold indicate significant differences
between the two groups.

We expected a small improvement score due to learning or retest effects in both

groups, but no difference in the magnitude of this effect between the two groups.

Results
Scores on primary and secondary measures at both time points are provided in Table 2.
At baseline, the groups were comparable on all primary and secondary measures.

Psychological and emotional well-being

A MANOVA was conducted to determine the effect of the between-subjects factor,
group, on the change scores in self-reported general psychological well-being (SCL-
90 z-score), depressive symptoms (average z-scores of depression measures), anxiety
symptoms (average z-scores of anxiety measures), and quality of life (QOLIBRI
z-score). A significant multivariate effect of group was found, Wilks’s Lambda = 0.780,
F(4, 70) = 4.928, p = .001. The effect size was large (partial η 2 = .22).
For each of the four measures individually, the effect of group was significant, with
large effect sizes for general psychological well-being, depression, and anxiety (partial
η 2 = .19, .17, and .18, respectively) and a moderate effect size for quality of life (partial
η 2 = .13). Table 3 displays the means and standard deviations on the three dependent
variables for both groups, as well as the associated p-values and effect sizes.
In terms of numbers of patients improving or remaining stable on the four measures,
the pattern was quite similar for each of the measures with about three-quarters of the
experimental group showing improvement, in most cases larger than half a standard
deviation. In the control group, on the other hand, rates of improvement or worsening
of symptoms were about equal for all variables, with changes of half a standard devi-
ation or larger seen only in a minority of cases.
 10 M. HOLLEMAN ET AL.

Table 3. Average change in primary outcome measures (z-score) from baseline to follow-up.
Experimental
group Control group
M SD M SD sig. (p) effect size
General psychological well-being 0.55 0.10 −0.08 0.11 <.001 0.19
Depression 0.66 0.12 −0.05 0.14 <.001 0.17
Anxiety 0.73 0.12 −0.02 0.14 <.001 0.18
Quality of life 0.64 0.12 −0.02 0.14 .001 0.13

Secondary measures
Neuropsychological measures
We expected a similar improvement from baseline to follow-up in both groups, due to
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test-retest or learning effects. The MANOVA was non-significant, Wilks’s Lambda =

0.910, F(3, 63) = 2.074, p = .113. However, all three cognitive domains showed a weak
trend of improved performance in the experimental group. Means and standard devi-
ations are provided in Table 4.
We repeated all the analyses with the dataset with the missing values. Without the
imputed data, the results were almost the same, but with higher partial η 2.

Discussion
Primary measures
Like much of the brain injury literature, our study highlights the prevalence of emotional
distress in the chronic phase of acquired brain injury. In this waiting-list controlled study,
we found that a comprehensive neuropsychological rehabilitation programme (Inten-
sive NeuroRehabilitation, INR) led to significant improvements in general psychological
well-being, depression, anxiety, and quality of life. There also seemed to be a trend
towards improved cognitive functioning in the experimental group. As all patients
were neurologically plateaued, these results cannot be attributed to spontaneous recov-
ery or to the passage of time.
Interestingly, the magnitude of the effect sizes of the change in psychological well-
being in general, and in depressive and anxious symptoms specifically, was at least com-
parable to the established effect of antidepressant medications as reported in three
meta-analyses (Kirsch et al., 2008; Turner, Matthews, Linardatos, Tell, & Rosenthal,
2008; Undurraga & Baldessarini, 2012).
Controlled studies investigating the psychosocial effects of comprehensive neurop-
sychological rehabilitation in the chronic phase are scarce, probably because of the
logistic problems involved. Geurtsen, Van Heugten, Martina, and Geurts (2010)

Table 4. Average change in secondary outcomes (z-score) from baseline to follow-up.

Experimental
group Control group
M SD M SD sig. effect size
Attention & processing speed 0.27 0.48 0.10 0.35 .12 0.037
Memory 0.21 0.42 0.02 0.54 .11 0.039
Executive function 0.12 0.53 −0.08 0.40 .11 0.039
 NEUROPSYCHOLOGICAL REHABILITATION 11

conducted a systematic review of holistic neuropsychological rehabilitation and con-

cluded that comprehensive rehabilitation programmes lead to a reduction in psychoso-
cial problems. Of the nine studies, included according to strict qualitative criteria, that
dealt with day-treatment programmes, two were randomised controlled trials (RCTs)
(Cicerone et al., 2008; Ruff & Niemann, 1990), four were non-randomised comparative
studies (Cicerone, Mott, Azulay, & Friel, 2004; Hashimoto, Okamoto, Watanabe, &
Ohashi, 2006; Rattok et al., 1992; Sarajuuri et al., 2005), and two were uncontrolled
cohort studies (Christensen, 1992; Malec, 2001). Our findings are in line with these
studies.
An RCT by Cicerone et al. (2008) compared a comprehensive, holistic neuropsycho-
logical programme with standard, multidisciplinary rehabilitation for people with
traumatic brain injury. They found greater improvement in quality of life, improved
self-efficacy for the management of symptoms, and better community integration in
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the experimental group. The authors suggest that this difference could be due to the
interventions directed at increasing self-regulation of cognitive and emotional pro-
cesses. They also note the possibly powerful effect of the group setting, emphasising
peer support and feedback. All of these elements are very similar to the INR programme.
Ruff and Niemann (1990) found psychosocial improvement (patients became less
socially withdrawn and less depressed) in both groups in an RCT comparing cognitive
remediation and problem-solving with a programme aimed at enhancing psychosocial
functioning and activities of daily living. However, inequality between the groups with
regard to coma duration was a possible confounder. Also, there was a lack of contrast
between the two treatments compared. Positive results on behavioural measures, intra-
and interpersonal functioning, competence and independence in daily life, and func-
tional abilities were found in the other studies. These studies also found improvement
in community integration, productivity, and number of working hours.
Two larger RCTs, including 120 and 360 patients, respectively (Salazar et al., 2000;
Vanderploeg et al., 2008), found no effects on behavioural or productivity outcomes.
However, these studies both included only veterans. Moreover, both studies involved
in-hospital treatment in a far more acute phase than our sample with average time
since injury ranging between five and seven weeks. Comprehensive treatment in the
acute phase arguably focuses on very different goals than in the chronic phase. For
instance, functional abilities will be attended to more in the acute phase, whereas in
the chronic phase, holistic neurorehabilitation revolves more around emotional and
psychosocial consequences of the injury.

Neuropsychological tests
There was only a weak trend of a differential effect of the programme on neuropsy-
chological performance. However, improving cognitive functions is not the aim of
the programme; rather, as all participants are neurologically plateaued, the pro-
gramme aims at providing psychoeducation, metacognitive knowledge and compen-
satory strategies in order for patients to deal more effectively with the cognitive
changes resulting from their injury. Therefore, we did not expect to find changes in
neuropsychological test performance. In their RCT comparing comprehensive neurop-
sychological rehabilitation to standard multidisciplinary rehabilitation, Cicerone et al.
(2008) did find significant improvement on neuropsychological tests in both groups.
However, as there were no repeated baseline assessments, it is not clear how much of
 12 M. HOLLEMAN ET AL.

this increase was due to retest effects. In our control group there were hardly any dis-
cernible retest effects.

Limitations
There are several limitations to this study. The relatively small sample size may have
resulted in diminished power. However, our study is larger than the few other RCTs
on holistic day treatment programmes in the chronic phase, whose sample sizes
range between 24 and 68 (Cicerone et al., 2008; Ruff & Niemann, 1990). As several
authors have pointed out, it is notoriously difficult to conduct research into comprehen-
sive neuropsychological rehabilitation programmes while adhering to strict methodo-
logical principles. Blinding is impossible and it is increasingly deemed unethical to
provide no treatment or even care as usual. Accrual is slow, as many of these pro-
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grammes serve only modest numbers of patients each year.

Another possible limitation is the fact that the members of the treatment team con-
ducted the assessments. This does not constitute a significant problem, as no change
was expected in the neuropsychological variables.
A strong feature is the design of this study, which is technically a waiting-list controlled
trial. But because allocation to the two groups depended only on time of referral, the out-
comes could be regarded as nearly as powerful as those of a randomised trial, since this
method of allocation is purely coincidental and does not involve any systematic biases
(the programme starts at different dates each year). Regarding the waiting-list design,
a relatively strong point of our study is that it does not consist of one single group sub-
jected to both waiting-list and experimental condition consecutively. Comparing the
results of two different groups is statistically stronger because it limits carryover effects.
One problem that results from the current design is the lack of controlled future
follow-up, as both groups have undergone the treatment. However, previous research
suggests that the results of comprehensive day treatment programmes with regard to
emotional well-being, societal participation, and productivity are maintained from
several months up to at least two years following treatment (Cicerone et al., 2008; Sar-
ajuuri et al., 2005).
A strong feature of the present study is the fact that we employed a conservative
method to deal with missing data (last observation carried forward/backward), allowing
analysis of all patients included in the study and minimising bias resulting from exclu-
sion of patients. Another strong point is the detailed description of the intervention and
the inclusion and exclusion criteria of the programme, and our adherence to CONSORT
guidelines.

Conclusion
The present study demonstrates solid effects of comprehensive, holistic neuropsycho-
logical rehabilitation on general psychological well-being, depression, anxiety, and
quality of life. Patients who have dealt with the detrimental psychosocial consequences
of their brain injury were able to make significant gains.

Acknowledgements
The authors wish to thank Anne Rienstra, Astrid Beerlage, Rick Horst, Arwen Pel, Marijn Luijpen, and José
de Vries for their help in the data collection.
 NEUROPSYCHOLOGICAL REHABILITATION 13

Disclosure statement
No potential conflict of interest was reported by the authors.

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