Journal of Behavioral and Brain Science, 2011, 1, 87-93
doi:10.4236/jbbs.2011.13012 Published Online August 2011 (http://www.SciRP.org/journal/jbbs)
Cognitive and Psychological Outcomes in Younger vs.
Older Children with Subtentorial/Supratentorial
Ependymoma after Radiation Therapy
Geraldina Poggi1, Annarita Adduci1, Lorenza Gandola2, Susanna Galbiati1,
Alessandro Degrate1, Elena Sironi1, Sandra Strazzer1, Maura Massimino2
1Scientific Institute E. Medea, Bosisio Parini, Italy
2National Tumo r Institute, Milan, Italy
Received March 28, 2011; revised April 20, 2011; accepted May 12, 2011
Abstract
Purpose: to investigate cognitive and psychological problems in children treated for intracranial ependy-
moma, the evolution of these disorders over time and the role of age at radiotherapy and tumor site, in their
onset and persistence. Methods and Materials: 23 patients received a complete evaluation; some of them
underwent follow-ups. The clinical data collected included sex, age (at diagnosis, assessment and tumor
treatment, thus dividing patients into two cohorts: younger or older than 5 years), site (supratentorial vs. sub-
tentorial), the presence of hydrocephalus, neurological examination, tumor treatment. All the patients re-
ceived an age-appropriate cognitive and psychological evaluation. Results: The mean cognitive level was
within the norm, with lower scores on the Performance Intelligence Quotient (PIQ). The psychological as-
sessment revealed Internalizing problems and impaired independence. Children older than 5 years had a
lower Intelligence Quotient (IQ) than the younger children, both at the initial evaluation and at follow-ups.
Initially, the supratentorial group appeared to be less impaired than the subtentorial group but then exhibited
a progressive decline in the IQ. In the subtentorial group, the children with an IQ within the normal range
remained stable at the follow-up, while the children with below-norm scores at the initial evaluation showed
deterioration over time. Conclusions: Tumor site seems to affect the cognitive outcome to a greater extent
than age at radiotherapy.
Keywords: Cognitive Outcome, Ependymoma, Children, Radiotherapy
1. Introduction
Studies on the cognitive outcome of patients with ependy-
moma are limited in number and are generally part of lar-
ger studies where ependymomas are compared with other
posterior fossa (PF) tumors such as medulloblastomas
and astrocytomas [1-4].
The most recent studies on cognitive and neuropsy-
chological outcomes show that patients treated for ependy-
moma do not present with severe cognitive impairment as
compared to other brain tumors, even though many of
them have neuropsychological problems (affecting me-
mory, attention, language and executive functions) which
often impair formal learning [5,6].
As for all brain tumors, age at diagnosis and the qual-
ity of surgery and radiotherapy are considered to be the
most important predictive factors for the onset of cogni-
tive and neuropsychological problems which have a great
impact on long-term survival [7-11].
The impact of radiation therapy was explored in Mer-
chant’s studies which showed how Conformal Radiation
Therapy (CRT) pointed out that supratentorial tumor
location, multiple surgery, male sex, longer symptomatic
interval, pre-CRT chemotherapy, endocrine deficiencies,
hydrocephalus, and young age at CRT were predictive
factors for academic problems [12-17].
In a recent work on 23 patients treated with local pos-
terior fossa irradiation who received one or more con-
secutive neuropsychological evaluations, von Hoff found
a moderate impairment of intellectual functions and iden-
tified early disease manifestation and treatment and post-
operative neurological deficits as the main risk factors

G. POGGI ET AL.
88
for the onset of cognitive problems. This study also em-
phasized that the neuropsychological difficulties can vary
in type and that no distinctive pattern of impairment can
be identified, unlike in other tumors [18].
The present study thus set out to:
1) Define the influence of age at radiotherapy as a
predictive factor by comparing two subgroups according
to age at radiotherapy (children younger than 5 years and
children older than 5 years).
2) Define the influence of tumor site as a predictive
factor by comparing two subgroups according to supra-
or subtentorial site.
3) Define the cognitive and psychological evolution of
the whole group’s cognitive profile over time.
2. Material and Methods
Patients
This study included the newly diagnosed patients treated
for ependymoma at the Pediatric Oncology Department
of the National Institute for Tumors of Milan in the time
period between 1993 and 2005, according to two con-
secutive national AIEOP (Italian Association of Pediatric
Hematology and Oncology) protocols.
In the 1994-2001 period, the patients with complete
tumor excision received hyperfractionated radiotherapy
(1.1 Gy twice a day) to the tumor bed plus 1 - 2 cm mar-
gins up to a total dose of 70.4 Gy. When the residual
tumor was documented after surgery, the patients first
received 4 chemotherapy courses with vincristine, eto-
poside and cyclophosphamide (VEC) plus/minus second-
look surgery, followed by the same radiotherapy sched-
ule (protocol 1) [19]. After 2001, the children with com-
plete tumor excision and grade 2 revised histology re-
ceived conformal radiation with conventional fractiona-
tion of 1.8 Gy/d up to a total dose of 59.4 Gy. The chil-
dren with complete tumor excision and grade 3 revised
histology received 4 VEC courses after radiotherapy. In
the presence of a residual tumor, of any grade, VEC was
prescribed before radiotherapy to facilitate second-look
tumor removal. In the event of there still being a tumor
after the second-look surgery, radiotherapy was com-
pleted with a boost delivered in two daily fractions of 4
Gy (protocol 2). Exclusion criteria included a history of
previous brain lesions (congenital or acquired), pre-ex-
isting acute or chronic serious illness and psychomotor
delay, as reported by the parents. All the patients re-
ceived at least one complete cognitive evaluation.
A total of 23 patients were included in the study. After
the initial assessment, some patients underwent further
evaluation: 13 patients were assessed only once, 10 pa-
tients twice, 6 patients 3 times and 4 patients 4 times.
The progressive reduction in number in the patients
participating in the follow-ups is due to that fact that
about half of the 23 patients initially evaluated lived at a
significant distance from their oncological centers and
our Institute to which they had been referred for a mul-
tidisciplinary clinical and functional evaluation at the end
of tumor treatment. These patients were then referred to
more easily accessible centers and did not undergo later
follow-ups.
All the participants gave their consent. The following
clinical and medical data were collected for all of them:
sex, age at diagnosis, age at assessment, age at tumor
treatment, time between diagnosis and assessment, his-
tological diagnosis, tumor site (supratentorial vs. subten-
torial), hydrocephalus, neurological examination and type
of tumor treatment (neurosurgery, chemotherapy and ra-
diotherapy).
3. Methods
Cognitive/Neuropsychological and Psychological
Evaluation
All the patients received an age-appropriate clinical cog-
nitive and psychological evaluation.
The cognitive assessment was performed using the
Wechsler Intelligence Scales-WPPSI-R, WISC-R [20, 21].
Attention, memory, executive functions, were also eva-
luated by age-appropriate tests (see Table 1).
The use of different tests did not allow for a quantita-
tive analysis of the neuropsychological evaluation: for
that reason, in this study, the only variable considered is
the presence or the absence of specific problems in those
investigated areas (attention, memory, executive func-
tions). Thus, a qualitative analysis was performed.
The psychological evaluation protocol was geared to
assess several aspects of psychosocial functioning. The
Child Behavior Checklist (CBCL ) [22] and the Vineland
Adaptive Behavior Scales-Expanded Form (VABS) [23]
were administered.
4. Statistical Analysis
Statistical analysis was conducted using SPSS software.
Table 1. Neuropsychological domain and test of measure-
ment.
Neuropsychological domain and test of measurement
Attention
 Conners’ Kiddie Continuous Performance
Test (K-CPT)
 Continuous Performance Test II (CPT II)
Memory
 Rey Figure – memory –
 Corsi Block – Tapping Test
 Digit Span
Executive Functions Wisconsin Card Sorting Test (WCST)

G. POGGI ET AL.
89
Data are presented as means and standard deviations
(SDs) for quantitative variables, and as frequencies and
percentages for qualitative variables. The scores of some
neuropsychological tests were transformed to Z-Scores.
A Z-score ≥ 2 was considered to be pathological.
With regard to the associations between cognitive-
psychological problems and site and age at radiotherapy,
the findings were compared by means of an Analysis of
Variance (ANOVA): multiple comparisons between sub-
groups of patients were performed based on age at ra-
diotherapy, site. A matched-pair t-test sample compared
the different evaluation outcome within the whole group.
A p value < 0.05 (two-tailed) was considered to be sig-
nificant.
5. Results
Sample Description at 1st Evalu ation
Table 2 shows the demographic and clinical characteris-
tics of the whole group (23 patients) at the first evalua-
tion.
As shown in Table 2, most of the patients had been
treated for a subtentorial ependymoma. Of these patients,
26% had developed hydrocephalus at tumor onset. Most
of the patients were treated according to Protocol 2. The
most frequently reported outcomes include motor prob-
lems, while sensory problems were found in a small
number of patients. No patient presented with epilepsy.
With regard to the cognitive evaluation, at the initial
assessment the group presented with mean Full Intelli-
gence Quotient (FIQ), Verbal Intelligence Quotient (VIQ)
and Performance Intelligente Quotient (PIQ) scores
within the norm, although four (17.4%) patients had an
FIQ below the norm.
In the neuropsychological test, 9 (39.1%) patients
showed attention problems, 5 (21.7%) patients had me-
mory problems and 9 (39.1%) patients had executive
function deficits.
With regard to the psychological evaluation, the most
frequently reported problem on the CBCL is Internaliz-
ing: 6 (26%) patients scored above the norm on the “In-
ternalizing” scale. The VABS shows a greater impair-
ment in the motor domain and independence. Table 2
also shows the mean scores obtained by the patients in
the psychological tests.
 Age at Radiotherapy
When radiotherapy was administered, 10 (43.4%) chil-
dren were aged < 5 years and 13 (56.5%) children were
aged > 5 years. When looking at the relationship between
age at radiotherapy and cognitive outcome, there is a
marked, yet not statistically significant, difference in IQ
between the two groups: the older children have a lower
mean IQ than the younger children. The difference in
FIQ is close to significance (p = 0.07). With regard to the
relationship between age at radiotherapy and psycho-
logical outcomes, the mean CBCL scale scores of the two
groups are similar. In contrast, the VABS scores show a
greater impairment in the older group, but this difference
is not significant.
 Tumor Site
With regard to the supra-/subtentorial distinction, the
initial cognitive evaluation revealed a greater impairment
in the subtentorial group, with VIQ, PIQ and FIQ scores
of 99.25, 91.58 and 96.6 in the subtentorial group and 102,
105.6 and 105 in the supratentorial group. The greater
impairment of the subtentorial group appears to be con-
firmed by the VABS scores evidencing an impairment in
independence and social skills. In contrast, the CBCL
scores do not show any relevant differences.
6. Evolution over Time
To study the cognitive, neuropsychological and psycho-
logical outcomes evolution over time we opted for a
qualitative analysis because of the attrition in the number
of patient participating to this research; we performed a
qualitative evaluation of each individual case and gave a
description of the progress over time in the 11 cases un-
dergoing follow-ups (see Table 3).
With regard to the initial evaluation, most cases were
within the norm: 20 patients had an IQ of over 75, but
three patients had a score below the norm; 11 patients
showed neuropsychological difficulties, but only 7 pa-
tients showed a deficit in all neuropsychological areas.
10 patients had psychosocial problems.
With regard to progress over time, 6 patients remained
stable or improved, and in all 6 cases these patients had a
history of subtentorial tumors. However, we noticed a
decline in the cognitive level of 5 patients at follow-up.
Of the latter, almost all (4 patients) had a supratentorial
tumor. The 5th patient had a subtentorial tumor. Unlike
the other cases who had average scores at the initial
evaluation, he already had an impaired cognitive level
attributable to neurological lesions and sensory impair-
ments which appeared after hydrocephalus at the tumor
onset and neurosurgery.
Of the 5 patients whose condition worsened, two be-
longed to the group of patients aged less than 5 years at
radiotherapy and three belonged to the group of patients
aged more than 5 years at radiotherapy.
With regard to the site, we observed a tendency to-
wards deterioration in patients with a supratentorial tu-
mor and a tendency towards stability-rather than an im-
provement in those with a subtentorial tumor, regardless
of age. The qualitative analysis revealed that site had a
greater influence than age on the progress of the cogni-

G. POGGI ET AL.
90
Table 2. Sample description at 1st evaluation.
DEMOGRAPHIC AN D CL INI CAL D ATA (23 pat ien ts )
Sex Male: 13 (56.5%)
Female: 10 (43.5%)
Mean age at Diagnosis 5.66 years (SD: 3.86 )
Mean age at Radiotherapy (years) 6.09 years (SD: 3.89)
Mean Time Diagnosis - Radiotherapy 0.34 (SD: 0.30)
Mean Time Diagnosis - 1st Evaluation 1.86 (SD: 2.63)
Age at 1st Evaluation (23 pt) 7.48 (SD: 4.29.)
Age at 2nd Evaluation (10 pt) 8.27 (SD: 4.58)
Demographic Data
Age at 3rd Evaluation (6 pt) 8.81 (SD: 4.17)
Tumor Site Supratentorial: 6 (26.1%)
Subtentorial: 17 (73.9%)
Hydrocephalus at onset Yes: 6 (26.1%)
No: 17 (73.9%)
Epilepsy 0 (0%)
Sensory Deficits
Reduced Visual Acuity: 1 (4.3%)
Strabismus: 2 (8.6%)
Reduced Hearing: 2 (8.6%)
Neurological examination Hemiparesis: 5 (21.7%)
Ataxia: 8 (34.7%)
Radiation therapy Protocol 1: 7 (30.4%)
Protocol 2: 16 (69.6 %)
Surgery Total excision at first surgery 16 (69%)
At second surgery 2 (8,6%)
Clinical Data
Chemotherapy Yes: 12 (52.1%)
No: 11 (47.9%)
COGNITIVE NEUROPSYCHOLOGICAL AND PSYCHOLOGICAL EVALUATION
FIQ 98.39 (SD: 19.02)
VIQ 100.06 (SD: 18.2)
PIQ 95.71 (SD: 21.53)
Internalizing 55.69 (SD: 10.9)
CBCL
Externalizing 48.19 (SD: 7.9)
Communication skills 90.8%
Daily Living skills 87.5%
Socialization 90.7%
VABS
Motor Skills 91.6%
tive situation over time.
7. Discussion
We studied the clinical and cognitive, neuropsychologi-
cal and psychological profiles of patients in order to re-
veal how age at radiotherapy and tumor site have influ-
ence in defining this profile, describing how this evolve
over time.
As compared to other populations, our sample fares
better from a clinical point of view in that our patients
did not exhibit severe motor or cognitive impairments.
Their outcomes are definitely more favorable than that of
patients who received whole brain irradiation [1-3]. The

G. POGGI ET AL.
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Table 3. Qualitative analysis.
PT Age at
Diagnosis Age at RT
Age at
First
Evaluation
Age
Group Tumor Site IQ at First
Evaluation
Cognitive
Evolution
over time
Attention
Problems Memory Problems
Executive
Function
Problems
Psycho-Social
Problems
1 26 29 36 < 5 Supra 110 DeteriorationNo / / Yes
2 37 45 51 < 5 Supra 123 DeteriorationNo No / No
3 17 20 28 < 5 Sub 112 // / / / Yes
4 12 14 24 <5 Sub 102 // / / / No
5 19 22 30 < 5 Sub 98 // / / / No
6 27 39 45 < 5 Sub 91 // / / / Yes
7 37 37 39 < 5 Sub 101 Stable / / / Yes
8 42 47 48 < 5 Sub 134 ImprovementNo No No No
9 48 56 178 < 5 Sub 67 // Yes Yes Yes Yes
10 50 55 65 < 5 Sub 117 // No No / No
11 54 56 58 < 5 Sub 113 ImprovementNo No No No
12 60 63 68 > 5 Supra 98 DeteriorationYes Yes Yes Yes
13 65 67 72 > 5 Supra 107 // Yes No No No
14 103 105 131 > 5 Supra 95 // No No No No
15 170 176 187 > 5 Supra 97 DeteriorationYes Yes Yes Yes
16 60 64 73 > 5 Sub 70 DeteriorationYes Yes Yes Yes
17 63 66 144 > 5 Sub 86 // Yes Yes Yes No
18 68 82 92 > 5 Sub 101 Stable Yes Yes Yes No
19 72 73 156 > 5 Sub 93 // No No Yes Yes
20 103 105 112 > 5 Sub 54 // Yes Yes Yes Yes
21 117 119 118 > 5 Sub 90 Stable Yes No Yes No
22 132 134 150 > 5 Sub 115 Stable No No No No
23 180 182 185 > 5 Sub 105 // Yes No No No
LEGEND: RT = radiotherapy; SUPRA = supratentorial site; SUB = subtentorial site.
most frequently reported motor impairments included
hemiparesis and ataxia in percentages similar to those
reported in the literature [1,3,17]. They are almost totally
attributable to a preoperative lesion or immediate post-
operative lesion.
At the cognitive and neuropsychological levels, the
mean scores of the whole sample are within the norm. The
same holds true for the PIQ scores which were lower
than the VIQ scores. The difference between PIQ and
VIQ is consistent with the literature.
On the whole, the picture was stable from a neuro-
psychological point of view as well; at the first evalua-
tion, 4 of the 7 patients with significant neuropsy-cho-
logical problems had scored below or at the lower limits
of the norm: these were patients with pre- or periopera-
tive damage. 3 patients had neuropsychological difficul-
ties which were associated with a subsequent deteriora-
tion of the cognitive level rather than an initial impair-
ment. The neuropsychological problems did not appear
to be necessarily associated to an impairment of the cog-
nitive level. This is in line with recent reports of core
problems (attention and memory problems) affecting aca-
demic performance, even in the presence of non-patho-
logical cognitive levels [24,25].
It is assumed that disorders of attention, memory and
executive functions—the functions underlying learning
—impair the normal functional development process and,
in so doing, affect contextual and school learning [26].
It is therefore necessary to perform repeat follow-ups
over time as the presence of disorders affecting the basic

G. POGGI ET AL.
92
neuropsychological functions could adversely influence
later cognitive development and planning, organization,
categorization and cognitive flexibility, thus interfering
with learning and interpersonal skills [24,25].
While investigating the outcome, relevant findings
emerged when we divided the patients into groups ac-
cording to age at radiotherapy and tumor site (supra- vs.
subtentorial). With regard to age we found a greater cog-
nitive impairment in the older patients at the initial eva-
luation than at the later follow-ups. Such a difference
was seen in both performance and verbal tests.
With regard to tumor site, we found a greater initial
impairment in patients with a subtentorial tumor, while
patients with a supratentorial tumor showed a more fa-
vorable initial pattern which however deteriorated pro-
gressively at the follow-ups, both in performance and
verbal tests.
In contrast, the subtentorial group remained stable or
improved during time, except for the patient with scores
below the limits of the norm at the initial cognitive eva-
luation who later exhibited a deterioration.
When looking at the most significant variables being
studied (age, site), the limited sample size and heteroge-
neity does not enable us to draw representative conclu-
sions on the differences in the clinical picture. However,
it can be stated that the younger patients who were treated
with radiotherapy do not appear to have a cognitive im-
pairment. Only one out of 11 patients showed a general-
ized cognitive impairment, with an association between
the below-the-norm IQ and neuropsychological psycho-
logical problems.
When interpreting this finding, it should be kept in
mind that only 6/11 patients in the younger group un-
derwent a neuropsychological evaluation (attention, me-
mory and executive functions) because the remaining
children were too young for these tests.
The most frequently observed psychological problems
are Internalizing problems. The result of the psychology-
cal evaluation which was performed on our sample is in
line with previous studies, which found the same kind of
disorders affecting this population of patients.
In conclusion, we can safely state that, in our sample,
tumor site seems to affect the cognitive outcome to a
greater extent than age at radiotherapy.
This emphasizes the need for similar studies on larger
samples which can provide a better insight into the mul-
tiplicity of cognitive, neuropsychological and psycho-lo-
gical profiles and enable a more detailed quantitative
analysis to be made, together with more generalizable con-
clusions. Such studies should be long-term, as longi-
tudinal observations enable better monitoring of the cog-
nitive, neuropsychological and psychological problems
and their impact on later cognitive development.
8. Acknowledgements
We gratefully acknowledge the financial support of
AIRC (Associazione Italiana per la ricerca contro il can-
cro).
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