Epilepsy Research (2015) 109, 210—218

journal homepage: www.elsevier.com/locate/epilepsyres

REVIEW

Cognitive rehabilitation in epilepsy:

An evidence-based review
Elisabetta Farina a, Alfredo Raglio b,c, Anna Rita Giovagnoli c,∗

a
Neurorehabilitation Unit, Laboratory for Treatment and Diagnosis of Acquired Cognitive Disorders,
S. Maria Nascente Clinical Research Center, Fondazione Don Carlo Gnocchi, Milano, Italy
b
Department of Biomedical and Specialistic Surgical Sciences, Section of Neurological Clinic,
University of Ferrara, Ferrara, Italy
c
Department of Diagnostics and Applied Technology, Fondazione IRCCS Istituto Neurologico C. Besta,
Via Celoria 11, 20133 Milano, Italy

Received 22 June 2014; received in revised form 19 October 2014; accepted 26 October 2014
Available online 6 November 2014

KEYWORDS Summary
Aim of the study: To review the modalities of cognitive rehabilitation (CR), outcome endpoints,
Epilepsy;
and the levels of evidence of efficacy of different interventions.
Cognitive deficits;
Methods: A systematic research in Pubmed, Psychinfo, and SCOPUS was performed assessing
Memory;
the articles written in the entire period covered by these databases till December 2013. Articles
Temporal lobe;
in English, Spanish or French were evaluated. A manual research evaluated the references of
Cognitive
all of the articles. The experimental studies were classified according to the level of evidence
rehabilitation
of efficacy, using a standardized Italian method (SPREAD, 2007), adopting the criteria reported
by Cicerone et al. (2000, 2011).
Results: Eighteen papers were classified into two reviews, four papers dealing with the princi-
ples and efficacy of CR in epilepsy, a methodological paper, a single-case report, a multiple-case
report, and nine experimental papers. Most studies involved patients with temporal lobe
epilepsy. Different types of CR were used to treat patients with epilepsy. A holistic rehabil-
itation approach was more useful than selective interventions to treat memory and attention
disturbances.
Conclusions: CR may be a useful tool to treat cognitive impairment in patients with epilepsy.
However, the modalities of treatment and outcome endpoints are important concerns of clinical
care and research. Controlled studies are needed to determine the efficacy of rehabilitation in
well-defined groups of patients with epilepsy.
© 2014 Elsevier B.V. All rights reserved.

∗ Corresponding author at: Department of Diagnostics and Applied Technology, Fondazione IRCCS Istituto Neurologico C. Besta, Via Celoria

11, 20133 Milano, Italy. Tel.: +39 02 23942344; fax: +39 02 70638217.
E-mail address: rgiovagnoli@istituto-besta.it (A.R. Giovagnoli).

http://dx.doi.org/10.1016/j.eplepsyres.2014.10.017
0920-1211/© 2014 Elsevier B.V. All rights reserved.
Cognitive rehabilitation in epilepsy: An evidence-based review 211

Contents

Introduction.............................................................................................................. 211
What is cognitive rehabilitation? .................................................................................... 211
Why cognitive rehabilitation in epilepsy? ............................................................................ 211
Material and methods .................................................................................................... 212
Results ................................................................................................................... 212
Paper categories .................................................................................................... 212
Modalities of cognitive rehabilitation................................................................................ 212
Experimental studies ................................................................................................ 212
Discussion ................................................................................................................ 216
Conclusions .............................................................................................................. 217
References ............................................................................................................... 217

Introduction interventions for attention, memory, social communication

What is cognitive rehabilitation?
Cognitive rehabilitation (CR) was defined as ‘‘Any interven-
tion strategy or technique which intends to enable clients or
patients, and their families, to live with, manage, by-pass,
reduce or come to terms with cognitive deficits precipi-
tated by injury to the brain’’ (Wilson, 1989). Therefore,
CR is not a restoration of cognitive functions but a com-
plex of activities aimed to compensate impaired functions by
incorporating individual and context-related demands. The
nature and severity of a cognitive handicap does not only
derive from the type and extent of brain damage but also
from a combination of positive and negative affects, person-
ality, behavioral changes, motivation, compliance, family
support, and physical environment. Recent literature (Choi
and Twamley, 2013; Ueda et al., 2013) maintains that CR
should respond to three main needs: a compensation of dys-
function, coping to psychosocial problems, and a limitation
of drug or surgery side effects. Moreover, the goals of CR
should be tailor-made, small, and concrete and its modal-
ity should reflect a patient’s perspectives and expectations
(e.g., return to work, schooling or homework, participation
in leisure and social activities), which may be a source of
strength or weakness. Specific cognitive gains and a gener-
alization of improvement to other cognitive functions are
other important goals of CR.
The benefits of CR have been described in patients
with traumatic brain injury (TBI) (Sohlberg et al., 2000),
stroke (Cicerone et al., 2000, 2011; Poulin et al., 2012) or
Alzheimer’s disease (Spector et al., 2003; Sitzer et al., 2006;
Orrell et al., 2014). The positive effects have been assessed
using the levels of evidence adopted in pharmacological tri-
als which are divided into class I (well-designed prospective
randomized controlled trials), class Ia (almost-randomized
trials), class II (prospective non-randomized controlled
trials), and class III (clinical series) with the possibility to
graduate the class II and III studies by adding positive or neg-
ative signs (e.g., class II++) (SPREAD, 2007; Cicerone et al.,
2011). Level A evidence is based directly on class I studies,
level B on class II studies, and level C on class III studies.
A recent review including 112 studies from 2003 to 2008
rated 14 studies as class I, five as class Ia, 11 as class II, and
82 as class III (Cicerone et al., 2011); the authors concluded
that there was a sufficient evidence to support standard
skills, and executive functions and a comprehensive-holistic
CR after TBI. Visuospatial rehabilitation after right hemi-
sphere stroke and selective interventions for aphasia and
apraxia after left hemisphere stroke were also considered
useful by a consensus group (Làdavas et al., 2011) and
guidelines of the European Federation of Neurological
Society (Cappa et al., 2005). Particular recommendations
regarded CR for selective neuropsychological deficits in the
post-acute stage after stroke or TBI, describing an evidence
level A, B or C.
Why cognitive rehabilitation in epilepsy?
Patients with epilepsy (PWE) may develop cognitive distur-
bances in relation to cortical dysfunctions caused by the
repetition and propagation of epileptic discharges, underly-
ing brain pathology, age of seizure onset, epilepsy duration,
seizure frequency, anti-epileptic drugs (AEDs) or surgery
(Dodrill and Matthews, 1992; Jones-Gotman et al., 1993;
Devinsky, 1995; Giovagnoli and Avanzini, 1999; Rausch,
1991). Mental slowing, anomia, decreased verbal fluency,
and executive, theory of mind, attention, and memory
disturbances are frequently observed in patients with drug-
resistant temporal (TLE) or frontal lobe epilepsy (FLE),
(Bell and Giovagnoli, 2007; Hermann et al., 2010; Jones-
Gotman et al., 2010; Klove and Matthews, 1966; Giovagnoli,
2014; Giovagnoli et al., 1996, 2011; Prevey et al., 1998;
Rausch, 1991). The prevalence of memory impairment in
patients with drug-resistant epilepsy is estimated around
20—50% (Halgren et al., 1991). Left TLE bears a signif-
icant risk of memory deficits compared with right TLE
(Hendriks et al., 2004). Moreover, patients with long-lasting
TLE may show a chronic cognitive deterioration (Hermann
et al., 2008, 2010). Although perceived cognitive failures
inconstantly correspond to objective deficits (Giovagnoli
et al., 1997; Hendriks et al., 2002; Ponds and Hendriks,
2006; Helmstaedter and Elger, 2008; Giovagnoli, 2013), both
self-rated and neuropsychological impairments may affect
quality of life (QoL) (Perrine et al., 1995; Giovagnoli et al.,
2014).
Different non-pharmacological interventions have been
used to alleviate the interictal disturbances associated with
epilepsy. Most studies have focused on psychosocial failures
(Gramstad et al., 2001; Suurmeijer et al., 2001; Tedman
et al., 1995), suggesting that a generic psychological support
212
or psychotherapy may help to overcome psychosocial hand-
icaps and seizure-related distress (Goldstein, 1997; Mittan,
2009). CR focusing on specific cognitive impairments has
been used to complement clinical care. However, a lack
of homogeneity in the methods of treatment and indica-
tors of outcome prevents reliable comparisons of results and
general conclusions.
In sum, there is evidence that some types of CR may alle-
viate cognitive impairments in patients affected by chronic
brain pathologies. Epilepsy often causes cognitive deficits
that increase the clinical burden and impair patients’ QoL.
CR could alleviate the clinical impact of cognitive distur-
bances but its methods and effects remain relevant issues
for clinical practice and research. This review evaluated the
literature concerning CR in epilepsy, aiming to describe the
modalities of treatment, the indicators of outcome, and the
levels of evidence of efficacy of different interventions.
Material and methods
A systematic research in Pubmed, Psychinfo, and SCOPUS
was performed. The following keywords were used to assess
the articles written in the entire period covered by these
databases till December 2013:
• Epilepsy [title] and cognitive [all fields] and rehabilitation
[all fields]
• Epilepsy [title] and cognitive [all fields] and ‘‘training’’
[all fields]
• Epilepsy [title] and cognitive [all fields] and intervention
[all fields]
• Epilepsy [title] and cognitive [all fields] and stimulation
[all fields]
• Epilepsy [title] and memory [all fields] and training or
education [all fields]
• Epilepsy [title] and neuropsychological [all fields] and
‘‘rehabilitation’’ [all fields]
• Epilepsy [title] and neuropsychological [all fields] and
stimulation [all fields].
Articles in English, Spanish or French were only included
in the search. A manual research evaluated the references
of all of the articles. The experimental studies were clas-
sified according to the level of evidence of effectiveness
or efficacy, using a standardized Italian method (SPREAD,
2007), adopting the criteria reported by Cicerone et al.
(2000, 2011).
Results
Paper categories
Eighteen papers were classified into two reviews (Engelberts
et al., 2002a; Shulman and Barr, 2002), four papers dealing
with the principles of CR in epilepsy or the measurements
of its efficacy (Arnedo et al., 2006; Marks et al., 2003;
Ponds and Hendriks, 2006; Ridsdale, 2009), a methodological
paper evaluating the inter-rater agreement of neurologists
and psychiatrists assessing responses to motor rehabilita-
tion and CR in children with epilepsy (Beghi et al., 2011), a
case report (Gupta and Naorem, 2003), a paper describing
E. Farina et al.
three clinical cases and the general principles and methods
of CR in epilepsy (Adelnkamp and Vermeulen, 1991), and
nine experimental papers (Bresson et al., 2007; Engelberts
et al., 2002b; Helmstaedter et al., 2007; Johanson et al.,
2001; Jones, 1974; Hendriks, 2001; Koorenhof et al., 2012;
Pfafflin and May, 2001; Schefft et al., 2008). Table 1 summa-
rizes the designs, treatments, endpoints, results, and levels
of evidence of the multiple case report and experimental
studies.
Modalities of cognitive rehabilitation
The rehabilitation programs for PWE have often adopted the
model methods applied in other neurological conditions. For
instance, both the use of external aids and internal mem-
ory strategies were previously used to treat memory decline
(Ponds and Hendriks, 2006). According to Ponds and Hendriks
(2006), the external aids can be classified into methods
that store the information externally (calendar, agenda,
hand-palm computer, mobile telephone, etc.), methods that
remind impaired people to perform a particular activity at
a specified time, and visual cues. The internal memory aids
comprehend verbal strategies (e.g., semantic associations)
and visual imagery strategies (e.g., face-name associations).
The rehabilitation of attention has used either direct train-
ing strategies, which represent the most frequent modality,
and compensatory approaches (Engelberts et al., 2002b;
Helmstaedter et al., 2007).
The CR methods may also be influenced by age. In chil-
dren, epilepsy is an ongoing process that changes with the
maturation of the central nervous system. Thereby, reha-
bilitation provides a framework for a dynamic treatment
plan addressing changing needs (Marks et al., 2003). In this
case, the term habilitation may be more proper than reha-
bilitation, guiding children toward their full potential. By
contrast, in adulthood, epilepsy may represent an isolated
clinical problem or a complication of an acute or chronic
disorder of the mature central nervous system.
Experimental studies
Forty years ago, Jones (1974) evaluated whether patients
with TLE submitted to right or left temporal lobe surgery
compensated memory deficits using mental imagery. All sub-
jects had to learn three lists of paired-associated words,
containing both concrete and abstract terms. The first list
was meant to provide a baseline of memory abilities; each
subject was asked to learn the second list using visual
imagery; afterwards, they were asked to put into practice
visual imagery, learning the third list. Differently from
amnesic patients, patients submitted to left temporal lobec-
tomy were able to compensate partially verbal memory
deficits, while patients with right temporal lobectomy per-
formed similarly to healthy controls. Although this study
did not test formally the generalization of learning strategy
to daily activities, three left TLE patients adopted mental
imagery as a mnemonic daily aid.
Pfafflin and May (2001) applied a comprehensive care
program in an epilepsy clinic using a prospective controlled
randomized design. Twenty percent of outpatients received
no AED, 50% of them had less than a seizure a month, and 40%
 Cognitive rehabilitation in epilepsy: An evidence-based review
Table 1 Experimental studies of cognitive rehabilitation in epilepsy.

Study design Participants Method Measurements of Highlights Study class Reference

efficacy

Observational 36 TLE patients Mental imagery Word list learning Patients submitted to II+ Jones (1974)
Immediate (18 left, 18 right) left temporal lobectomy
follow-up 2 amnesic patients partially compensated
36 controls verbal memory deficits
by using visual imagery
Randomized 42 inpatients 50 days cognitive training, Self-developed Improved quality of life II++ Pfafflin and
50-days treatment 64 outpatients psychotherapy, occupational measure of daily Reduced seizure May (2001)
Immediate 114 waiting list training, and counseling performance frequency.
follow-up controls Quality of life Correlation between
(unspecified quality of life and
epilepsy) seizure frequency
Observational 22 patients with Epilepsy education. Quality of life Improvement at both III Johanson et al.
8-weeks treatment. complex partial Body awareness and relaxation. Multidimensional measures (2001)
Immediate and seizures Creative activities. symptom self-raring
6-months Cognitive training.
follow-ups Completion of a personal diary
Observational 21 patients A course book explaining the Neuropsychological Increased use of III Hendriks (2001)
Immediate and (unspecified relationship between memory tests, self-evaluation strategies for everyday
3-months follow-up epilepsy) problems and epilepsy and scales, and memory memory in everyday life
memory structure, enhancing scales Memory improvement at
insight. short- and long-term
Group meeting on learning follow-up. Increased
strategies and planning of coping ability with
individual actions for memory memory difficulties.
problems.
Randomized 46 patients with Computer-based Retraining Computerized Improvement in II++ Engelberts
Six individual focal seizures Method for attention. attention tests, neuropsychological et al. (2002b)
weekly one-hour Compensation Method using Auditory Verbal tests, self-reported
sessions strategies for attention deficits Memory Test, cognitive outcome, and
Immediate and relying on external stimuli, non-computerized quality of life
6-months follow-up stimulating daily routines, and Stroop Color Word
reducing task complexity Task, self-rating of
cognitive functions,
quality of life

213
 214
Table 1 (Continued)

Study design Participants Method Measurements of Highlights Study class Reference

efficacy

Controlled 112 TLE patients Meta-cognitive therapy Verbal learning Improved verbal learning II+ Helmstaedter
One-month submitted to left (psycho-education about brain Figural memory in right TLE patients et al. (2007)
treatment or right temporal functioning and cognitive Attention tests
Immediate lobectomy deficits), learning
follow-up compensatory strategies,
attention, problem solving,
learning, and mnemonics
exercises
Computer based cognitive
exercises focused on attention,
memory and executive
functions.
Occupational therapy.
Socio-therapy (group
communication and interaction
in outdoor activities, sports,
painting or designing).
Individual counseling.
Observational 30 patients with Internal memory aids Learning Word list learning III Bresson et al.
TLE (14 with left improvement in left (2007)
TLE, 16 with right TLE patients
TLE)
Observational 54 patients with Self-generation encoding Neuropsychological Cognitive improvement III Schefft et al.
TLE strategy. tests after using (2008)
8 patients with Passive didactic strategy. self-generation encoding
FLE strategy in conjunction
with external cues
Observational 50 TLE patients Computer-based brain training. Memory test and Improvement of III Koorenhof
Three sessions (for submitted to left Training to use external self-rating self-rated memory and et al. (2012)
a maximum of four temporal memory aids and internal Hospital Anxiety and mood
hours) lobectomy 23 memory strategies Depression Scale
Short-term patients, 27
follow-up controls
Observational 3 patients Compensatory strategy for Learning of strategies Improvement of memory III Adelnkamp and

E. Farina et al.
submitted to memory on jobs and awareness Vermeulen
amygdalectomy (1991)
TLE, temporal lobe epilepsy; FLE, frontal lobe epilepsy.
Cognitive rehabilitation in epilepsy: An evidence-based review
received one drug, while 4% and 30% of inpatients and wait-
ing list patients, respectively, received one or more AEDs.
CR was combined with psychotherapy, occupational training,
and individual counseling. Self-evaluation of daily perform-
ances and QoL was completed before and after treatment.
QoL improved and seizure frequency decreased in 40% of
patients treated by CR compared with 23% of the waiting-list
patients, although the mean changes were not significant.
QoL improvement related to seizure reduction.
Hendriks (2001) described a rehabilitation program for
memory, including the use of a course book aimed to improve
insight and group meetings to discuss learning strategies.
Assessment was performed before and at the end of the
treatment, with a brush-up session three months later.
Patients and their relatives indicated that the participants
were significantly more acquainted with strategies suppor-
ting memory in everyday life and their memory did improve.
They also reported a better ability to cope with memory dif-
ficulties. Significant improvements were also noticed at the
brush-up session on most of the long-term memory tests.
However, the paper did not describe any quantitative data
or control subjects.
Engelberts et al. (2002b) evaluated adult outpatients
with focal seizures and attention impairment, treated with
carbamazepine. Nineteen patients were randomly assigned
to a Retraining Method based on the direct retraining of
attention using computerized tasks. Seventeen patients
were assigned to a Compensation Method which provided
strategies for attention deficits, relying on external infor-
mation storage systems, developing daily routines, and
reducing tasks’ complexity by means of a step-by-step
strategy. Eight patients were included in a waiting-list.
Assessment was completed before training, immediately
after it, and six months later. At the immediate and
six-months follow-ups, the training-related performances
improved in both treatment groups compared with controls.
The Compensation Method was more effective in improv-
ing self-reported cognitive abilities and QoL, in particular in
patients with low educational levels. Attention, as measured
by the Stroop Color Word Task, did not show any change.
Patients with uncontrolled seizures benefitted from CR more
than seizure free patients.
Bresson et al. (2007) evaluated the usefulness of differ-
ent internal memory aids in patients with TLE and memory
disturbances candidates to surgery. The effect of memory
aids was different in two patient subgroups. Compared with
patients with right TLE and normal controls, on word list
learning, patients with left TLE took little advantage from
cued recall and phonemic processing, which is supported
by the left hemisphere cortex (Berman et al., 2003). How-
ever, patients with left TLE highly benefitted from semantic
processing. These findings underline the need to differenti-
ate the type of cognitive strategies in epilepsy rehabilitation
according to the location of brain damage: patients with
left TLE should be instructed to process information more
deeply, generating self-reference or self-generated cues,
while patients with right TLE may be helped by any kind
of cue.
Schefft et al. (2008) showed that a self-generation encod-
ing strategy was more effective than a passive didactic
strategy in patients with left (n = 25) or right TLE (n = 29)
or frontal lobe epilepsy (n = 8), but only if it was used
215
in conjunction with external cues. As the authors stated,
the greater help derived from an internal self-generated
strategy is not surprising because similar findings were also
shown in healthy subjects and patients affected by differ-
ent neurological disorders (traumatic brain injury, multiple
sclerosis, Alzheimer’s disease, Parkinson’s disease). Unfor-
tunately, the authors did not furnish any data about the
generalization of this internal strategy to daily life.
Helmstaedter et al. (2007) investigated as to whether a
holistic program of CR may help to remediate neuropsychol-
ogical impairment after temporal lobectomy. Two groups of
patients with drug-resistant TLE submitted to temporal lobe
resection were treated (n = 55) or not treated (n = 57) by
postoperative CR. All patients were evaluated using memory
and attention tests before and three months after surgery.
Randomization was not possible owing to funding problems;
the rehabilitated group was recruited in one clinic and the
control age-matched group in another. However, the authors
stated that ‘‘groups were matched as far as possible with
respect to gender, age at surgery, age of epilepsy onset,
side and type of surgery, handedness, and estimated IQ or
education’’. No detail was given about the pharmacologi-
cal treatment. A verbal learning test provided three scores:
learning (the total number of words correctly reproduced
over five learning trials), memory (the number of words lost
that were remembered between the last immediate recall
and the delayed recall), and recognition. Figural memory
was assessed using the revised version of the German figural
design list-learning test. Psychomotor speed and attention
were assessed by means of a letter cancelation task. Results
showed that attention improved independently on rehabili-
tation. There was a rehabilitation effect on verbal learning
and recognition only in patients with right TLE, while no
effect was seen for verbal delayed recall. This indicated
that the positive effects of rehabilitation may be linked
to the neocortical aspects of verbal learning rather than
to the medial temporal aspects of long-term consolidation
and retrieval. Patients with left TLE, who were most in
need of rehabilitation, obtained less benefits than right TLE
patients. The authors concluded that, after right temporal
lobe surgery, the left hemisphere-mediated learning may
remain available and may be recruited by training, while
this would not be possible after left hemisphere surgery.
Another study on patients with TLE was performed by
Koorenhof et al. (2012). This short report documented a
preliminary evaluation of the acceptability and short-term
efficacy of an outpatient memory rehabilitation program in
patients with TLE submitted to left temporal lobectomy.
The study also investigated whether a computer-based train-
ing could determine any additional benefit and whether
training delivered before surgery had any advantage over
post-surgical training. Fifty participants were enrolled in
the study and 42 of them completed the program; dropping
out was due to a lack of time to attend the sessions or to
complete the homework. Information concerning the brain,
memory functions, and factors affecting memory in epilepsy
were provided. Furthermore, instructions were given about
external memory aids (‘‘traditional’’ or ‘‘modern’’, such
as mobile phones and computers) and internal memory
strategies (imagery, the Method of Loci, the Story Method).
Participants were encouraged to use the external and
internal strategies in daily situations and were assigned
216
homework (paper and pencil exercises, behavioral tasks).
As part of the program, participants were also provided
with up to 40 15-min sessions based on a computer-based
training delivered via the Internet, focusing on memory,
concentration, mental flexibility, cognitive control, and
processing speed. Memory was evaluated using parallel
tests and self-rating of everyday performances. Participants
also completed the Hospital Anxiety and Depression Scale.
After training, no significant gain was detected on mem-
ory tests even though some participants showed better
performances. Self-ratings indicated memory improvement,
which was significant only in the left temporal lobectomy
group. Positive memory changes were associated with mood
improvement. Compared with postoperative rehabilitation,
preoperative rehabilitation was not associated with a better
outcome.
Johanson et al. (2001) described an eight-weeks holistic
rehabilitation program in small epilepsy groups, based on
a person-centered team approach. This program had dif-
ferent goals: improving the ability to cope with seizures
and their cognitive consequences, increasing meta-memory,
ameliorating QoL, developing techniques for a self-control
of seizures, and obtaining practical information about
epilepsy-related problems and inherent resources. Classes
were run twice a week and lasted 4 h a day. The pilot
study used this method in 21 participants most of whom
were affected by complex partial seizures with or with-
out generalization. However, there was no control group,
PWE were only evaluated using two self-reported meas-
ures (QoL, multidimensional symptoms assessment), and
no neuropsychological tests were employed. Both measures
showed significant positive changes: some psychological and
Qol aspects improved at the end of the program and other
aspects improved at the six-months follow-up. Interestingly,
very positive qualitative changes were reported at a 5-years
follow-up.
In Adelkamp and Vermeulen’s (1991) study, three PWE
with anterograde memory deficits caused by bilateral amyg-
dalectomy, viral encephalitis or head injury were assessed
after rehabilitation. Patients were unaware of their memory
deficits and their causes. Two of them gained partial aware-
ness and learned compensatory strategies to be applied in
their jobs, while the third patient only ameliorated in aware-
ness but did not develop any compensatory strategy in daily
life because his work was highly complex. No quantitative
data were reported.
A case study (Gupta and Naorem, 2003) dealt with a
32-year-old man with secondary generalized epilepsy that
started at eight years, associated with attention, concen-
tration, and memory deficits. The rehabilitation program
comprised a psychological support therapy and cognitive
training including paper and pencil tasks and real-life activ-
ities aimed to stimulate selective and sustained attention,
to reduce interference effects, to develop compensatory
memory strategies, and to shift attention among competing
stimuli. The training program covered six weeks including
an hour session a week and home exercises. Results showed
an improvement of global cognitive functions, attention,
memory, executive abilities, emotional status, and indepen-
dency.
Based on the evidence level of efficacy, two out of nine
experimental studies were attributed to class II++, two to
E. Farina et al.
class II+, and five to class III. Therefore, the level of evidence
was B for the attention deficits and C for the memory deficits
(Table 1).
Discussion
This review shows that there is a limited evidence of
efficacy for CR in epilepsy. The number of experimental
studies in this field is small and some of them suffer from
important biases, such as a lack of randomization (Jones,
1974; Hendriks, 2001; Helmstaedter et al., 2007) or control
groups (Hendriks, 2001) and small sample sizes (Jones, 1974;
Engelberts et al., 2002a; Koorenhof et al., 2012). These
studies are not homogeneous when considering the partici-
pants (types of epilepsy, surgical and non-surgical patients)
and the duration or type of intervention (holistic, as in
Pfafflin and May, 2001; Helmstaedter et al., 2007; Johanson
et al., 2001; selective, as in Engelberts et al., 2002b; Schefft
et al., 2008).
Out of the studies reported in this review, one found no
significant results (Pfafflin and May, 2001), while another
showed modest effects (Koorenhof et al., 2012). Some stud-
ies reporting a positive influence for CR only described
qualitative changes, which prevents a clear-cut assess-
ment of the efficacy of the treatments (Adelnkamp and
Vermeulen, 1991; Hendriks, 2001; Johanson et al., 2001).
A relevant result based on neuropsychological tests
assessing verbal learning and recognition was that patients
with right TLE responded to CR more significantly than
patients with left TLE (Helmstaedter et al., 2007). Other
studies revealed that patients submitted to left temporal
lobectomy were partially able to compensate their ver-
bal memory deficits using visual imagery (Jones, 1974) or
to take advantage from the use of semantic strategies for
verbal learning (Bresson et al., 2007). Patients with left
TLE also reported subjective memory improvement after
a holistic rehabilitation program (Koorenhof et al., 2012).
A possible confounding effect of AEDs was never specifi-
cally considered. These findings suggest that the choice of a
rehabilitative intervention should take into account epilepsy
laterality and clinical and pharmacological variables. Fur-
thermore, the majority of studies showing benefits from
CR involved patients with TLE, suggesting that some of the
pathophysiological and clinical features of TLE may be spe-
cific indications to CR.
The holistic rehabilitation approach has strong theoret-
ical bases and a major advantage in that it addresses both
cognitive and behavioral problems that cause psychosocial
disabilities. The efficacy of such an approach in PWE should
be confirmed by adequate methodologies, considering that
a multi-professional work needs a great amount of time and
economic sustainability. The length of a holistic program
may also be an obstacle, as suggested by studies on patients’
compliance (Koorenhof et al., 2012). The generalization of
the benefits of CR to functions not directly involved by the
training and its impact on everyday skills remain uncertain,
although internal strategies, such as mental imagery, have
been used as mnemonic aids in daily life (Jones, 1974).
To conclude, these results provide some support than
CR may be a useful resource to alleviate cognitive distur-
bances and consequent psychosocial difficulties in PWE, in
Cognitive rehabilitation in epilepsy: An evidence-based review
particular in patients with TLE. PWE, who frequently retain
good insight and have selective impairments, could exhibit
a better response to CR compared to patients with other
neurological disorders, such as a stroke or TBI. A comprehen-
sive rehabilitation approach focusing not only on cognitive
deficits but also on personal, social, and physical aspects,
based on a multidisciplinary team approach, could provide
an opportunity of clinical improvement beyond seizure
control. Recommendations for future studies include the
assessment of large patient groups with multicenter recruit-
ment, the use of standardized high quality interventions, the
planning of randomized controlled studies, and long-term
follow-ups. A relevant concern remains the choice of the
indicators of efficacy. Measures of outcome assessing the
generalization of the effects to various cognitive domains
and daily performances should be adopted. Neuropsychol-
ogical tests should have an ecological value and should be
combined with measures of perceived abilities, autonomy,
and QoL.
Conclusions
In selected PWE, attention and memory may benefit from
CR. In these patients, a holistic approach including tail-
ored training and compensation strategies may be more
useful than selective interventions. Controlled studies in
well-defined patients groups are needed to document the
efficacy of well-defined rehabilitation therapies.
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