J Neurooncol (2014) 118:385393
DOI 10.1007/s11060-014-1449-7
CLINICAL STUDY
Weight of epilepsy in brain tumor patients
Marta Maschio Francesca Sperati Loredana Dinapoli
Antonello Vidiri Alessandra Fabi Andrea Pace
Alfredo Pompili Carmine Maria Carapella Tonino Cantelmi
Received: 16 December 2013 / Accepted: 16 April 2014 / Published online: 1 May 2014
Springer Science+Business Media New York 2014
Abstract About 2040 % of patients with brain tumor
have seizures; all of whom must be treated with antiepi-
leptic drugs (AEDs) that can cause side effects which may
influence quality of life (QoL). However, little data are
available regarding the weight of epilepsy on QoL in brain
tumor (BT) patients, despite the fact that epilepsy is con-
sidered the most important risk factor for long-term dis-
ability in this patient population. Aim of this study is to
explore the weight of epilepsy in BT patients, and to
identify which factors might contribute to their epilepsy
burden, as expressed by them only at their first visit in a
specialized epilepsy center, in order to have a snapshot for
M. Maschio (&)
L. Dinapoli
T. Cantelmi
Center for Tumor-related Epilepsy, Area of Supporting Care,
Regina Elena National Cancer Institute, Via Elio Chianesi 53,
00144 Rome, Italy
e-mail: maschio@ifo.it
F. Sperati
Biostatistics/Scientific Direction, Regina Elena National Cancer
Institute, Via Elio Chianesi 53, 00144 Rome, Italy
A. Vidiri
Department of Radiology, Regina Elena National Cancer
Institute, Via Elio Chianesi 53, 00144 Rome, Italy
A. Fabi
Department of Oncology, Regina Elena National Cancer
Institute, Via Elio Chianesi 53, 00144 Rome, Italy
A. Pace
Neurology Unit, Department of Neuroscience and Cervical-
facial Pathology, Regina Elena National Cancer Institute, Via
Elio Chianesi 53, 00144 Rome, Italy
A. Pompili
C. M. Carapella
Neurosurgery Division, Department of Neuroscience and
Cervical-facial Pathology, Regina Elena National Cancer
Institute, Via Elio Chianesi 53, 00144 Rome, Italy
that moment in their care cycle. We reviewed medical
charts and results from a battery of tests (routinely given at
our outpatient center), administered to 100 consecutive
BTRE patients at their first visit, followed from 2007 to
2010. Our results reveal: (1) neurological performances
and global neurocognitive status were not influenced by
factors related to neoplastic disease or to epilepsy (2) side
effects, cognitive deficits, and QoL concerns, as well as
patients perception of these, were significantly related to
polytherapy, especially in patients who had been taking
AEDs for a period longer that 6 months (3) the seizure
number did not influence patients QoL. We found that the
weight of epilepsy in BTRE patients was related to AED
therapy. Our study highlights the fact that epilepsy in our
patients adds a significant burden, and suggests the need to
give the proper attention to patients concerns regarding the
challenges that this pathology might present. Nevertheless,
future studies could be designed with a follow-up period
and with a patient stratification in order to better under-
stand the weight of epilepsy for these patients.
Keywords Antiepileptic drugs
Brain tumor-related
epilepsy
Brain tumor
Quality of life
Introduction
From the physicians perspective, patients with brain
tumor-related epilepsy (BTRE) represent a sum of many
challengestherapeutic, support, and psychosocial, that
result from treating an individual who has two serious
pathologies simultaneously: on one hand, the brain tumor,
and on the other hand, epilepsy [1]. In fact BTRE patients
may require medical attention for a variety of unique
concerns: epileptic seizures, possible serious collateral
123
386
effects of antineoplastic and antiepileptic therapies, phys-
ical disabilities and/or neurocognitive disturbances corre-
lated to the tumor site [2, 3]. From the patient perspective,
in addition to the cancer diagnosis, the burden of epilepsy
can add distress to his/her coping with the brain tumor
(BT). In fact, literature data indicates that in these patients,
the presence of epilepsy is considered the most important
risk factor for long-term disability [35]. To date, there are
numerous studies that address the impact of BT on quality
of life (QoL), [68]. However, there is only one published
study [9] to date regarding the weight of epilepsy on the
QoL in this patient population. This paucity of studies
exists despite the fact that 2040 % of patient with BT
have seizures as presenting symptom and about 2045 %
will develop them throughout the course of the disease [3];
all of whom must be treated with antiepileptic drugs
(AEDs) that can cause collateral effects which may influ-
ence their QoL [911].
We decided to undertake a retrospective study on BTRE
patients who came to our center for brain tumor-related
epilepsy, in order to explore the weight of epilepsy in this
patient population, and to identify which factors might
contribute to this epilepsy burden, as expressed by them
only at their first visit, in order to have a snapshot for that
moment in their care cycle. Our center is a specialized
epilepsy center certified by LICE (Italian League against
Epilepsy) that is located within an oncological hospital
(Regina Elena National Cancer Institute) and for this rea-
son, there is a constant collaboration with oncologists
regarding the care of our patients. This type of collabora-
tion facilitates a multidisciplinary, integrated approach to
epilepsy and to BT, on the part of different specialists.
Patients arrive at our center already having received a
diagnosis of epilepsy and in treatment, or they are coming
for a first diagnosis. Patients can be referred to us from a
number of sources: from oncologist within our hospital or
from other hospitals; from their Public Health System
general practitioner; from other specialists; or on their own
(without having been referred).
To achieve this aim, we examined the medical charts
and results from a battery of neuropsychological/QoL tests
routinely administered at their first visit.
Materials and methods
Medical charts and results from a battery of neuropsy-
chological/QoL tests of 100 consecutive patients with
BTRE, were reviewed for two typologies of patients: (1)
patients following a first epileptic seizure due to BT, and
not yet taking AEDs (2) BTRE patients who had been
referred from other institutions (i.e. not specialized in
epilepsy) who were already taking AEDs. All materials
123
J Neurooncol (2014) 118:385393
reviewed were from patients who had come to our out-
patient center for their first visit, during the period
20072010. The following data were collected:
Demographic characteristics
1. Histological types of BT: metastases, meningiomas,
low grade and high-grade gliomas.
2. Seizure type, according to the International Classifica-
tion of Seizures [12]: simple partial (SP), complex
partial (CP), simple partial plus secondary generalized
tonicclonic seizures (SP ? SGTC), complex partial
plus secondary generalized tonicclonic seizures
(CP ? SGTC).
3. Number of seizures in the month preceding the first
visit to our center: one or more than 1 seizures per
month.
4. Antiepileptic therapy at first visit: yes or no.
5. Type of AEDs: old (carbamazepine, clobazam, phe-
nytoin, phenobarbital, valproic acid); new (lamotri-
gine, levetiracetam, oxcarbazepine, pregabalin,
topiramate, zonisamide); polytherapy.
6. Duration of AED therapy: B6 months and [6 months.
7. Reason for changing AEDs: persistence of seizures;
adverse events; persistence of seizure plus adverse
events.
8. Chemotherapy (CT)/radiotherapy (RT) received prior
to visit (to our center): yes or no.
9. Scores on the following tests:
a. Karnofsky Performance Status (KPS) and the
Barthel Index (BI) [13, 14] for evaluation of
personal autonomy and independence.
b. Mini Mental State Examination (MMSE) [15], for
evaluation of global cognitive performance.
c. European Organization for Research and Treat-
ment of Cancer Quality of Life Questionnaire-C30
(EORTC QLQ-C30). This is a cancer-specific,
structured questionnaire designed for use in clin-
ical trials; it contains 30 questions that evaluate
global QoL, symptoms and functional abilities
[16].
d. Quality of Life in Epilepsy-31 (QOLIE-31) ques-
tionnaire (version 2), This is an adaptation of the
original QOLIE-31 instrument and is a 31-item
questionnaire. It includes seven subscales (Seizure
Worry whose questions are about patients feel
about seizures during the past 4 weeks, Overall
QoL whose question asks about how patients feel
about overall quality of life, Emotional Wellbeing,
Energy/Fatigue (both) whose questions are about
how patients have been feeling during the past
4 weeks, Cognitive Functioning whose questions
386
effects of antineoplastic and antiepileptic therapies, phys-
ical disabilities and/or neurocognitive disturbances corre-
lated to the tumor site [2, 3]. From the patient perspective,
in addition to the cancer diagnosis, the burden of epilepsy
can add distress to his/her coping with the brain tumor
(BT). In fact, literature data indicates that in these patients,
the presence of epilepsy is considered the most important
risk factor for long-term disability [35]. To date, there are
numerous studies that address the impact of BT on quality
of life (QoL), [68]. However, there is only one published
study [9] to date regarding the weight of epilepsy on the
QoL in this patient population. This paucity of studies
exists despite the fact that 2040 % of patient with BT
have seizures as presenting symptom and about 2045 %
will develop them throughout the course of the disease [3];
all of whom must be treated with antiepileptic drugs
(AEDs) that can cause collateral effects which may influ-
ence their QoL [911].
We decided to undertake a retrospective study on BTRE
patients who came to our center for brain tumor-related
epilepsy, in order to explore the weight of epilepsy in this
patient population, and to identify which factors might
contribute to this epilepsy burden, as expressed by them
only at their first visit, in order to have a snapshot for that
moment in their care cycle. Our center is a specialized
epilepsy center certified by LICE (Italian League against
Epilepsy) that is located within an oncological hospital
(Regina Elena National Cancer Institute) and for this rea-
son, there is a constant collaboration with oncologists
regarding the care of our patients. This type of collabora-
tion facilitates a multidisciplinary, integrated approach to
epilepsy and to BT, on the part of different specialists.
Patients arrive at our center already having received a
diagnosis of epilepsy and in treatment, or they are coming
for a first diagnosis. Patients can be referred to us from a
number of sources: from oncologist within our hospital or
from other hospitals; from their Public Health System
general practitioner; from other specialists; or on their own
(without having been referred).
To achieve this aim, we examined the medical charts
and results from a battery of neuropsychological/QoL tests
routinely administered at their first visit.
Materials and methods
Medical charts and results from a battery of neuropsy-
chological/QoL tests of 100 consecutive patients with
BTRE, were reviewed for two typologies of patients: (1)
patients following a first epileptic seizure due to BT, and
not yet taking AEDs (2) BTRE patients who had been
referred from other institutions (i.e. not specialized in
epilepsy) who were already taking AEDs. All materials
123
J Neurooncol (2014) 118:385393
reviewed were from patients who had come to our out-
patient center for their first visit, during the period
20072010. The following data were collected:
Demographic characteristics
1. Histological types of BT: metastases, meningiomas,
low grade and high-grade gliomas.
2. Seizure type, according to the International Classifica-
tion of Seizures [12]: simple partial (SP), complex
partial (CP), simple partial plus secondary generalized
tonicclonic seizures (SP ? SGTC), complex partial
plus secondary generalized tonicclonic seizures
(CP ? SGTC).
3. Number of seizures in the month preceding the first
visit to our center: one or more than 1 seizures per
month.
4. Antiepileptic therapy at first visit: yes or no.
5. Type of AEDs: old (carbamazepine, clobazam, phe-
nytoin, phenobarbital, valproic acid); new (lamotri-
gine, levetiracetam, oxcarbazepine, pregabalin,
topiramate, zonisamide); polytherapy.
6. Duration of AED therapy: B6 months and [6 months.
7. Reason for changing AEDs: persistence of seizures;
adverse events; persistence of seizure plus adverse
events.
8. Chemotherapy (CT)/radiotherapy (RT) received prior
to visit (to our center): yes or no.
9. Scores on the following tests:
a. Karnofsky Performance Status (KPS) and the
Barthel Index (BI) [13, 14] for evaluation of
personal autonomy and independence.
b. Mini Mental State Examination (MMSE) [15], for
evaluation of global cognitive performance.
c. European Organization for Research and Treat-
ment of Cancer Quality of Life Questionnaire-C30
(EORTC QLQ-C30). This is a cancer-specific,
structured questionnaire designed for use in clin-
ical trials; it contains 30 questions that evaluate
global QoL, symptoms and functional abilities
[16].
d. Quality of Life in Epilepsy-31 (QOLIE-31) ques-
tionnaire (version 2), This is an adaptation of the
original QOLIE-31 instrument and is a 31-item
questionnaire. It includes seven subscales (Seizure
Worry whose questions are about patients feel
about seizures during the past 4 weeks, Overall
QoL whose question asks about how patients feel
about overall quality of life, Emotional Wellbeing,
Energy/Fatigue (both) whose questions are about
how patients have been feeling during the past
4 weeks, Cognitive Functioning whose questions
J Neurooncol (2014) 118:385393 387

are about thinking, reading, concentrating and Table 1 Descriptive, clinical, epileptological and oncological char-
memory problems patients may have had during acteristics of patients (n = 100)
the past 4 weeks, Medication Effects whose ques- Age (Mean 50.2 14.7
tions are about problems patients may have related years SD)
to epilepsy or antiepileptic medication, Social Gender n (%) M 53 (53)
Function whose questions are about how patient F 47 (47)
feel and about problems they may have with daily Education (years) 5 14 (14)
activities during the past 4 weeks) and the Health n (%)
Status item. Higher scores always reflect better 8 22 (22)
performance. An extra item is added to each of the 13 43 (43)
seven subscales asking the patient to grade his or 18 21 (21)
her overall distress related to the topic of each Marital status n (%) Married 70 (70)
subscale. Higher scores reflect greater distress Single 15 (15)
[17]. Widower/Widow 9 (9)
e. Adverse Events Profile. This is brief 19-item Divorced 6 (6)
instrument used to reduce adverse effects of AEDs Origin/region n (%) Lazio 82 (82)
and improve subjective health status. A score Other 12 (12)
ranging from 19 to 76 may be calculated to Job n (%) No 12 (12)
measure the total side effect burden of a medica- Yes 43 (43)
tion regimen [18]. A higher score corresponds to Student 4 (4)
heavier side effect. No, because of disease 22 (22)
The study was approved by the Institutes Ethical Retired 19 (19)
Committee. Reason for first visit to Seizures 69 (69)
our center n (%)
Adverse events 5 (5)
Statistical analysis
Seizures ? diagnosis of 23 (23)
tumor
We computed descriptive statistics for all variables of Seizures ? relapse 3 (3)
interest. Continuous data were reported as means and
Seizure number in 1 per month 25 (25)
standard deviations, while we represented categorical data month prior
with frequencies and percentage values. We evaluated the To first visit to our >1 per month 75 (75)
normal distribution of the data using the ShapiroWilk or center n (%)
KolmogorovSmirnov normality test, when appropriate. Seizure type n (%) SP 39 (39)
We applied the KruskallWallis test to compare all the CP 9 (9)
used tools for evaluation of QoL, and their different SP ? SGTC 24 (24)
domain scores, based on the histology (metastases, CP ? SGTC 28 (28)
meningioma, low-grade glioma and high-grade glioma), Histology n (%) Metastases 18 (18)
type of AEDs at first visit (old AED, new AED and Meningioma 14 (14)
polytherapy) and duration of AED therapy (no therapy, Low grade glioma 17 (17)
B6 months and [6 months). High grade glioma 51 (51)
Specifically regarding the variable AEDs at first visit, Surgery n (%) No 26 (26)
we grouped carbamazepine, clobazam, phenytoin, pheno- Yes 74 (74)
barbital and valproic acid as old AEDs; while lamotri- Radiotherapy n (%) No 56 (56)
gine, levetiracetam, oxcarbazepine, pregabalin, topiramate, Yes 44 (44)
zonisamide were considered as new AEDs. Chemotherapy n (%) No 63 (63)
We applied the MannWhitney test to compare all tests Yes 37 (37)
according to the following dichotomous variables: seizures AED at first visit n (%) Old AED 47 (47)
number in the month at first visit to our center (1 seizure
CBZ 5
per month and [1 per month), AED therapy (no and yes),
PB 36
RT (no and yes) and CT (no and yes).
PHT 1
We used the Pearsons Chi squared test to assess the rela-
VPA 5
tionships between the AED therapy at first visit and the fol-
New AED 23 (23)
lowing categorical variables: seizure number in the months

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Table 1 continued Table 2 Mean scores of all tests (n = 100)

LEV 4 Mean SD
LTG 1
KPS 93.8 10.6
OXC 13
Barthel 93.9 10.9
TPM 5
MMSE 28.1 2.3
None 22 (22)
EORTC QLQ-C-30 Functional scale 74.3 20
Polytherapy 8 (8)
Symptoms scale 18.5 17.7
OXC ? LEV
QoL 66.5 20.8
OXC ? VPA
QOLIE 31P(V2)
CBZ ? PB
Seizure worry 63.4 28.2
PB ? CNZ ? PHT ? OXC
Overall QoL 62.5 20.1
PB ? OXC ? LTG
Emotional wellbeing 65.9 23
PB ? PGB ? TPM ? OXC
Energy/Fatigue 56.5 23.5
LTG ? VPA ? LEV
Cognitive effects 71.2 28.4
PB ? PGB
AED effects 68 28.8
Modification of AED None 10 (10)
Social function 69.1 27.4
at first visit n (%) Yes, persistence of seizures 50 (50)
Health thermometer 58.3 22.7
Yes, adverse events 33 (33)
Distress (related to) Seizure worry 2.6 1.3
Yes, persistence of seizure 7 (7)
and adverse events Overall QoL 2.3 1.2
Emotional wellbeing 2.5 1.3
AED antiepileptic drug, SP simple partial, CP complex partial, SGTC
Energy/Fatigue 2.6 1.2
secondarily generalized tonicclonic
Cognitive effects 2.4 1.5
CBZ carbamazepine, CNZ clobazam, LEV levetiracetam, LTG lamo-
trigine, OXC oxcarbazepine, PB phenobarbital, PHT phenitoine, PGB AED effects 2.6 1.2
pregabalin, TPM topiramate, VPA valproic acid Social function 2.4 1.3
AEP 35 11.1

prior to first visit at our center, the reason for AED modifi-
cation following the first visit (none, persistence of seizures,
adverse events and persistence of seizure plus adverse events)
and changes in AEDs after the first visit (no and yes). No effort
was made to correct for multiple comparisons.
All data were collected retrospectively and analysed
with SPSS statistical software version 20 (SPSS Inc.,
Chicago IL, USA).
Results
Descriptive clinical, epileptological and oncological char-
acteristics are described in Table 1.
Table 2 shows the mean scores obtained at all tests.
Regarding KPS, BI, and MMSE, scores were in the normal
ranges.
Statistical comparisons
Histologies: mean scores of the tests used to evaluate QoL
did not show any significant differences among the various
histologies (data not shown).
Seizure number (in the month prior to the first visit): the
number of seizures varies from 1 to 90 and the distribution
presents a strong skewness that limits its use as a
AED antiepileptic drug, KPS Karnofsky Performance Status, BI
Barthel Index, MMSE Mini Mental State Examination, AEP Adverse
Event Profile
continuous variable in the statistical analysis. Seizure
number in the month before: Range (190) Mean 7.9 SD
15.9 Median 2. For mean scores on all test utilized, pre-
sence of either one or more than 1 seizure/month showed
no significant impact (see Table 3).
AED therapy (presence/absence of), effects of therapy
on tests results: there were significant effects of AED
therapy on the following: patients under AED therapy
showed worse results on subscale of QOLIE 31-P cog-
nitive effects (p = 0.037), adverse effects (p = 0.004)
and social function (p = 0.009) and on the subscale
related to distress on cognitive effect (p = 0.024) and
drugs (p \ 0.001) compared with patients not taking
AED therapy, independently of the AEDs used (Table 4).
Effect of different AED therapies (on mean tests scores):
the group of patients with polytherapy showed the worst
results on the subscale of QOLIE31-P adverse effects
(p = 0.045) and health thermometer (p = 0.046). More-
over, this group of patients had higher scores on the AEP
test than patients with old and new therapy (mean SD:
48.6 13.5; 34.9 11.4; 34.3 10.0 for polytherapy,
new AED, old AED respectively. p = 0.021) (Table 5).

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Table 3 Comparison of mean scores of all tests, according to seizures number in the month before
Seizures number in the month before
1 [1 MannWhitney
n = 27 n = 73
Mean SD Mean SD p value

KPS 95.5 8.0 93.1 11.4 0.463

Barthel 95.5 8.0 93.3 11.7 0.605
MMSE 28.7 2.1 27.9 2.4 0.114
EORTC QLQ-C30 Functional scale 78.4 17.3 72.7 20.8 0.280
Symptoms scale 19.7 19.8 18.0 17.0 0.597
QoL 68.4 19.7 65.8 21.3 0.602
QOLIE 31P(V2)
Seizures worry 56.8 25.3 65.9 28.9 0.113
QoL 66.3 20.1 61.1 20.1 0.295
Emotional wellness 63.7 16.5 66.7 25.1 0.142
Energy fatigue 54.9 22.4 57.1 24.0 0.697
Cognitive effects 76.7 25.1 69.1 29.5 0.317
AE effects 70.0 23.2 67.2 30.7 0.909
Social function 71.1 25.8 68.3 28.1 0.758
Health thermometer 59.6 20.5 57.8 23.6 0.506
Distress(related to) Seizure worry 2.8 1.3 2.5 1.3 0.269
Overall QoL 2.4 1.0 2.3 1.2 0.678
Emotional wellbeing 2.5 1.1 2.5 1.3 0.908
Energy/fatigue 2.4 1.1 2.6 1.2 0.484
Cognitive effects 2.0 1.3 2.5 1.5 0.145
AED effects 2.5 1.0 2.6 1.3 0.656
Social functions 2.4 1.5 2.4 1.3 0.936
AEP 33.7 9.9 35.5 11.6 0.600
AED antiepileptic drug, KPS Karnofsky Performance Status, BI Barthel Index, MMSE Mini Mental State Examination, AEP Adverse Event
Profile

Duration of AED therapy: the duration of AED therapy
varies from 0 to 108 months and the distribution presents a
strong skewness that limits its use as a continuous variable
in the statistical analysis. Duration of AED therapy: Range
(0108) Mean 7 SD 15.2 Median 1. Among patients who
had taken AED therapy for more than 6 months, the worse
the results of the tests on subscale of QOLIE31-P cog-
nitive effects (p = 0.001), adverse effects (p = 0.001)
and social function (= 0.029); on the subscale related to
distress on cognitive effect (p = 0.014) and drugs
(p = 0.001) and on AEP test (p = 0.015) (Table 6).
Change in AED therapy: of the patients arriving at our
center who had had to change their AED therapy, we found
that of the patients who had assumed new AEDs, 56 %
necessitated a change in AED. Of those who had taken an
old AED or polytherapy, 100 % had necessitated a change
in AED therapy (data not shown). As indicated in Table 1,
changes in AED therapy were made for reasons only due to
inefficacy, side effects or both.
Chemotherapy and radiotherapy (presence/absence of):
when we evaluated the effect of presence/absence of CT
and presence/absence of RT on mean scores of neurolog-
ical performances tests (KPS and BI), global neurocogni-
tive status (MMSE) and EORTC QLQ-C-30 we observed
no statistical differences (Table 7).
Discussion
These results were obtained from a retrospective study
comprised of a chart review of BTRE patients who had
come to our specialized epilepsy center, regarding only the
data pertaining to their first visit. Concerning the weight of
epilepsy in these patients, our results indicate that at the first
visit to our center, QoL was significantly influenced by the
presence, type and duration of AED therapy, but not by the
number of seizures. First, patients assuming AEDs (inde-
pendently of the AED used) perceive significantly more

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Table 4 Comparison of mean scores of all tests, according to AED therapy at first visit
AED therapy at first visit
No Yes MannWhitney
n = 22 n = 78
mean SD mean SD p value

KPS 90.9 13.4 94.6 9.6 0.185

BI 90.7 13.8 94.9 9.8 0.123
MMSE 27.7 2.6 28.2 2.3 0.390
EORTC QLQ-C30 Functional scale 78.8 16 73 20.9 0.355
Symptoms scale 19.6 18.3 18.1 17.6 0.770
QoL 66.2 20.9 66.6 20.9 0.848
QOLIE 31P(V2)
Seizure worry 72 30.6 61 27.2 0.070
Overall QoL 64.6 20 61.9 20.2 0.841
Emotional well-being 71.1 17.8 64.5 24.2 0.440
Energy/fatigue 56.5 25.3 56.5 23.1 0.874
Cognitive effects 80.2 27.8 68.6 28.2 0.037
AED effects 83.1 22.4 63.7 29.1 0.004
Social function 80.1 2.5 66 26.5 0.009
Health thermometer 50.9 19.5 60.4 23.2 0.056
Distress (related to) Seizure worry 2.6 1.4 2.6 1.3 0.891
Overall QoL 2.1 1.1 2.4 1.2 0.278
Emotional wellbeing 2.2 1.3 2.6 1.3 0.186
Energy/fatigue 2.5 1.1 2.6 1.2 0.959
Cognitive effects 1.8 1.4 2.5 1.5 0.024
AED effects 1.8 1 2.8 1.2 <0.001
Social function 2 1.2 2.5 1.3 0.150
AEP 31.6 9.2 36 11.5 0.124
Bold values indicate p \ 0.05 is statistically significant
AED antiepileptic drug, KPS Karnofsky Performance Status, BI Barthel Index, MMSE Mini Mental State Examination, AEP Adverse Event
Profile

negative effects on cognition, social function and adverse
effects of AEDs, with respect to patients who had not taken
AEDs. The patients assuming AEDs also had a significantly
higher distress related to cognitive effect and to the presence
of drugs. This could mean that patients consider the anti-
epileptic therapy as a negative influence on their cognitive
functioning and QoL, independently of the AED used.
Moreover, in our patient population, patients assuming AED
polytherapy perceive significantly more adverse effects of
AEDs and have a worse perception of their health with
respect to patients in AED monotherapy. These data are in
line with those in the literature that indicate a higher number
of adverse events and a worsening of QoL for epileptic
patients who assume polytherapy [19]. In addition, we
observed that patients with longer AED therapy (indepen-
dently of AED used) perceive significantly more negative
effects on cognition, social function and adverse effects of
AEDs with respect to patients having had a therapy
B6 months. They also have significantly higher distress
related to cognitive effects and to the presence of drugs and
demonstrate heavier side effects. This is the first time that
data have shown that in this patient population, the duration
of AED therapy can have a significant influence on patients
QoL; the longer the therapy, the more negatively the AEDs
impacted patients social and cognitive spheres.
Another significant finding from this study is the fact
that the seizure number did not influence patients QoL in
BTRE patients. That means that whether there is one sei-
zure or many, the patients perception of his/her QoL did
not change; what weighs on the patient is the diagnosis of
epilepsy, that brings with it a host of other QoL concerns:
the need to take drugs, the fear of side effects and the
distress over not having a meaningful social life. This is in
line with literature data that points to side effects as
affecting perception of QoL in non oncological epileptic
patients, more than seizure frequency [2022].

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Table 5 Comparison of mean scores of all tests, according to type of AED therapy at first visit
AED at first visit KruskallWallis
old AED new AED polytherapy
n = 47 n = 23 n=8
Mean SD Mean SD Mean SD p value

KPS 94.2 9.5 93.9 11.2 98.7 3.5 0.436

BI 94.2 10.0 94.8 10.8 98.7 3.5 0.436
MMSE 28.2 2.3 28.1 2.4 29.0 1.4 0.699
EORTC QLQ-C30 Functional scale 73.8 20.8 72.4 22.8 69.7 17.1 0.689
Symptoms scale 17.0 18.3 19.8 18.4 20.1 11.1 0.436
QoL 69.7 17.7 64.9 25.2 53.1 21.8 0.165
QOLIE 31P(V2)
Seizure worry 62.0 27.8 63.2 28.0 49.2 19.9 0.307
Overall QoL 63.0 17.0 61.2 24.7 58.1 25.5 0.937
Emotional well-being 68.5 20.7 58.0 29.3 59.1 25.8 0.350
Energy/fatigue 60.6 20.6 51.1 27.4 48.1 21.5 0.224
Cognitive effects 71.0 25.8 70.1 31.0 50.1 30.5 0.144
AED effects 69.2 27.2 59.6 31.5 43.4 24.1 0.045
Social function 62.3 26.5 70.1 26.4 76.0 25.3 0.252
Health thermometer 66.8 19.0 52.6 24.2 45.0 31.2 0.046
Distress (related to) Seizure worry 2.6 1.5 2.5 1.2 2.7 0.9 0.847
Overall QoL 2.3 1.0 2.6 1.5 2.4 1.2 0.826
Emotional wellbeing 2.5 1.2 2.8 1.4 3.0 1.2 0.417
Energy/fatigue 2.5 1.2 2.5 1.2 3.0 1.3 0.564
Cognitive effects 2.5 1.5 2.3 1.5 3.1 1.5 0.489
AED effect 2.7 1.3 2.9 1.0 3.2 0.9 0.523
Social function 2.5 1.4 2.6 1.3 2.5 1.2 0.879
AEP 34.3 10.0 34.9 11.4 48.6 13.5 0.021
Bold values indicate p \ 0.05 is statistically significant
AED antiepileptic drug, KPS Karnofsky Performance Status, BI Barthel Index, MMSE Mini Mental State Examination, AEP Adverse Event
Profile

Our data appear to confirm the work by Klein [9] that
demonstrates a worse QoL in BTRE patients with respect
to BT patients; due to the side effects of AED therapy and
to the burden of the diagnosis of epilepsy.
Finally, our study reveals that neurological perfor-
mances (evaluated by KPS and BI) and global neurocog-
nitive status (even if evaluated only by MMSE, considered
a basic instrument) were not influenced either by factors
related to the neoplastic disease or by factors related to
epilepsy and related treatments. These results are consistent
with other studies in which patients with BT have good
functional recovery [23] and their daily lives and functional
performances do not appear to be limited by seizure
number [9]. However, the aim of this study was to bring to
the fore the burden of epilepsy in this patient population,
rather than of the neoplastic disease, which in any event,
would require specific methods and dedicated research
designs. The MMSE, which is comprised in the battery of
tests routinely given at our center, is actually too broad for
the evaluation of possible effects of pharmacological
therapy on the cognitive sphere. The evaluation of the
possible effect of AEDs on cognition, in both BTRE and
non-oncological epilepsy, is usually done with a more
structured battery of tests [2429]. Finally, in our patients,
QoL did not seem to have been influenced by the different
histology. However patients having arrived at our center
had all been in a phase of illness that still allowed complete
autonomy, and therefore, possible differences in QoL due
to a histological differentiation might not have been dis-
tinguishable yet.
In conclusion, our study highlights the fact that epilepsy
in our patients with BTRE adds a significant burden, and
suggests the need to give the proper attention to patients
concerns regarding the challenges that this pathology might
present. Nevertheless, future studies could be designed
with a follow-up period and with a patient stratification in
order to better understand the weight of epilepsy for these
patients.

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392 J Neurooncol (2014) 118:385393

Table 6 Comparison of mean scores of all tests, according to duration of AED therapy prior to first visit
Duration of AED therapy
No therapy B 6 months [ 6 months KruskallWallis
n = 22 n = 56 n = 22
Mean SD Mean SD Mean SD p value

KPS 90.9 13.4 93.6 10.5 97.3 6.3 0.139

BI 90.7 13.8 93.9 10.8 97.3 6.3 0.143
MMSE 27.7 2.6 28 2.2 28.9 2.3 0.119
EORTC QLQ-C30
Functional scale 78.8 16 72.8 21.5 73.5 19.5 0.633
Symptoms scale 19.6 18.3 17.9 19.3 18.6 12.9 0.645
QoL 66.2 20.9 67.4 22.4 64.4 16.9 0.844
QOLIE 31P(V2)
Seizure worry 72 30.6 63.2 28.2 55.5 24.2 0.086
Overall QoL 64.6 20 63 20.6 59.3 19.4 0.752
Emotional well being 71.1 17.8 64.5 24.4 64.3 24.4 0.708
Energy/fatigue 56.5 25.3 58.8 23.5 50.8 21.8 0.395
Cognitive effects 80.2 27.8 74.7 26.9 53.1 26.1 0.001
AED effects 83.1 22.4 68.1 28.7 52.6 27.6 0.001
Social function 80.1 28.5 66.7 27.1 64.2 25.3 0.029
Health thermometer 50.9 19.5 62 23.5 56.4 22.6 0.129
Distress (related to) Seizure worry 2.6 1.4 2.7 1.4 2.5 1.2 0.928
Overall QoL 2.1 1.1 2.4 1.3 2.4 0.9 0.541
Emotional wellbeing 2.2 1.3 2.6 1.3 2.6 1.2 0.409
Energy/fatigue 2.5 1.1 2.5 1.3 2.6 1.1 0.890
Cognitive effects 1.8 1.4 2.4 1.5 2.9 1.3 0.014
AED effects 1.8 1 2.8 1.2 2.9 1.2 0.001
Social function 2 1.2 2.5 1.4 2.4 1.2 0.356
AEP 31.6 9.2 33.9 10.7 41.2 12 0.015
Bold values indicate p \ 0.05 is statistically significant
AED antiepileptic drug, KPS Karnofsky Performance Status, BI Barthel Index, MMSE Mini Mental State Examination, AEP Adverse Event
Profile

Table 7 Comparison of mean scores of tests according to RT/CT

Radiotherapy Chemotherapy
No Yes MannWhitney No Yes MannWhitney
n = 56 n = 44 n = 63 n = 37
Mean SD Mean SD p-value Mean SD Mean SD p value

KPS 94.6 10.3 92.7 11.1 0.324 94.6 9.8 92.4 11.9 0.425
Barthel 94.4 10.7 93.4 11.2 0.641 94.9 9.6 92.3 12.7 0.424
MMSE 28.2 2.3 27.9 2.4 0.519 28.2 2.1 28.0 2.7 0.988
EORTC QLQ-C30 Functional scale 72.6 22.5 76.3 16.3 0.773 74.6 20.7 73.7 19.0 0.513
Symptoms scale 21.3 20.8 14.8 11.9 0.300 18.4 18.0 18.5 17.4 0.999
QoL 66.6 22.2 66.3 19.1 0.677 66.0 21.3 67.3 20.2 0.889
KPS Karnofsky Performance Status, BI Barthel Index, MMSE Mini Mental State Examination

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