http://informahealthcare.com/bij ISSN: 0269-9052 (print), 1362-301X (electronic) Brain Inj, Early Online: 1–8 ! 2014 Informa UK Ltd. DOI: 10.3109/02699052.2014.975281
ORIGINAL ARTICLE
Long-term functional outcome of patients with cerebellar pilocytic astrocytoma surgically treated in childhood N. Ait Khelifa-Gallois1, F. Laroussinie1, S. Puget2, C. Sainte- Rose2, & G. Dellatolas1 INSERM U669, Univ Paris Sud, Univ Paris Descartes, Paris, France and 2Pediatric Neurosurgery Department, Necker Enfants Malades Hospital, Paris, France
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Abstract
Keywords
Purpose: A number of studies report neurological and cognitive deficits and behavioural disorders in children after surgical treatment for a benign cerebellar tumour. The present study explores functional outcome in adolescents and adults treated for a low-grade cerebellar astrocytoma in childhood. Materials and methods: Participants were 18 adolescents and 46 adults treated for low-grade astrocytoma in childhood. Academic achievement, professional status and neurological, cognitive and behavioural disturbances were collected using self-completed and parental questionnaires for adolescents and phone interview for adults. For the adolescent group, a control group filled in the same questionnaires. Results: Mean time lapse from surgery was 7.8 years for adolescents and 12.9 years for adults. Five adults (11%) had major sequelae related to post-operative complications, post-operative mutism and/or brain stem involvement. All the other participants presented close-to-normal academic achievement and normal autonomy, despite a high rate of reported cognitive difficulties and difficulties related to mild neurological sequelae (fine motor skills, balance). Conclusion: The long-term functional outcome of low-grade cerebellar astrocytoma is generally favourable, in the absence of post-operative complications and brain stem involvement. No major impact of neurological deficits, cognitive problems and emotional disorders on academic achievement and independent functioning was observed.
Cognitive difficulties, learning difficulties, long-term functional outcome, low-grade cerebellar astrocytoma, neurological sequelae, QoL
Introduction Pilocytic astrocytoma has an overall incidence of 0.37 per 100 000 persons per year [1] and a high survival rate—94% at 10 years—which is by far the best for any glial tumour [2]. After surgery, the tumour does not generally recur, although careful evaluation with neuroimaging is recommended in the years following surgery [3, 4]. Patients surgically treated for these tumours are generally considered to be cured [5]. However, despite their benign biological nature, an increasing number of studies have reported that low-grade cerebellar astrocytomas can cause not only permanent neurological symptoms related to cerebellar dysfunction (e.g. ataxia, dysmetria, nystagmus, dysarthria) [6], but also cognitive deficits. Schmahmann and Sherman [7] described a ‘cerebellar cognitive affective syndrome’ in adults with acquired cerebellar lesions, which is characterized by deficits in executive functions, linguistic processing, spatial cognition and affect regulation. Impairments in planning and sequencing, visual–spatial functions, expressive language, verbal memory, verbal fluency, attention, processing speed and
Correspondence: Nadira Ait Khelifa-Gallois, INSERM U669, 16 avenue Paul Vaillant Couturier, 94807, Villejuif, France. Tel: 0145595392. Fax: 0145595331. E-mail: [email protected]
History Received 2 May 2014 Revised 11 September 2014 Accepted 7 October 2014 Published online 5 November 2014
regulation of affect have been described in patients who underwent resection of a cerebellar tumour in childhood without additional therapy [8–10]. Likewise, behavioural deficits, impairments in interpersonal relationships, and academic difficulties have been reported in survivors of childhood low-grade astrocytoma [10, 11]. In addition, specific difficulty in learning to read has been attributed to cerebellar dysfunction [12]. Reports that cerebellar lesions produce intellectual and behavioural deficits make it important to determine the outcome of children with low-grade astrocytoma and the impact of the neurological, cognitive and behavioural difficulties described on long-term academic achievement, autonomy and quality-of-life. In fact, little is known about the long-term outcome after resection of a low-grade cerebellar astrocytoma. The impairments in intelligence, memory, language, attention, academic skills and psychosocial function that have been reported [13] have been frequently observed in groups that have undergone not only cerebellar resection but also cranial irradiation and/or chemotherapy [8]. Additionally, it can be remarked that the questionnaires used in studies that evaluate long-term outcome of low-grade cerebellar astrocytoma were developed to evaluate sequelae in brain tumours in general [5, 6]. A few studies used questionnaires to assess long-term outcome. Pompili et al. [5] used a questionnaire to assess the
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quality-of-life (QoL) of adults surgically treated for cerebellar pilocytic astrocytoma in childhood and concluded that, by traditional standards, these patients appear to fare quite well. Nevertheless, their self-reported life experience was less satisfactory than that of the control group. These authors emphasized the role of psychosocial factors in complete recovery and good quality-of-life. Daszkiewicz et al. [14] observed that the long-term functional outcome of juvenile cerebellar pilocytic astrocytoma was relatively favourable, in spite of permanent neurological deficits and emotional disorders in over half of the patients. These did not, however, preclude normal education and independent functioning. Finally, Zuzak et al. [6] concluded that children treated for low-grade cerebellar astrocytomas have a low risk of neurological, cognitive, emotional and behavioural complications when compared with other paediatric brain tumours and that their quality-of-life was similar to that of healthy controls. The present study used questionnaires and phone interviews focusing on neurological difficulties classically related to cerebellar dysfunction on one hand and to cognitive and behavioural difficulties as described in the literature after cerebellar damage on the other. In a group of adolescents and adults treated for a low-grade cerebellar astrocytoma, the aims were: (i) to collect self-completed or parental reports of neurological, cognitive and behavioural difficulties; (ii) to examine academic achievement, professional status and autonomy; and (iii) to explore whether negative outcomes, if present, are associated with specific risk factors. The present report includes two studies; the first, in adolescents, used self-completed and parental questionnaires to describe neurological, cognitive and behavioural difficulties and academic situation; and the second, in adults, used a semistructured interview to provide a description of reported difficulties and present life situation.
Study 1: Adolescents Methods Participants Inclusion criteria were: (1) surgically treated cerebellar astrocytoma during childhood at the Paediatric Neurosurgery Department of Necker Enfants Malades Hospital in Paris; (2) being aged 12–18 years in the year of the present study. Twenty-five adolescents corresponded to these criteria. Contact with adolescents and their parents or legal caregivers was made by the consulting physician, who gave or sent the parents an envelope containing an explanatory letter, an informed consent form and two questionnaires, one for the adolescent and the second for the parents. They were asked to return the informed consent and the questionnaires completed. Contact failed for six adolescents (impossible to find the address); four of them were living in countries other than France. One family refused to participate. Eighteen adolescents completed the self-report questionnaire and 17 of their parents completed the parental questionnaire. Information available concerning the non-participants about their present school situation and from the medical files did not show any significant difference between participants
Brain Inj, Early Online: 1–8
and non-participants. Seventeen healthy control adolescents recruited in ordinary schools of the same age, gender and parental education level, and 15 of their parents, completed the same questionnaires. Materials Medical data. From the medical files, information was
gathered about the history of the illness (i.e. age at diagnosis, age at surgery), type of surgery, presence of pre-operative hydrocephalus, recurrence of the tumour and secondary surgery and post-operative complications. The adolescent self-report and the parental questionnaire, presented in the Appendix, were developed by the present authors and based on previous experience from clinical investigations in children with brain tumours [15, 16]. The adolescent self-report included (i) a General Questionnaire concerning socio-demographic data, educational history, everyday difficulties and rehabilitation; (ii) a questionnaire about neurological, cognitive and academic difficulties (see Appendix). The parental questionnaire included (i) a General questionnaire concerning sociodemographic data, educational history, whether the school staff were aware of the illness, rehabilitation and satisfaction with the medical care received and rehabilitation; (ii) questions about present type of school frequented, current learning difficulties (i.e. slowness, attention, memory, language, academic or behavioural difficulties); (iii) the Global Evaluation Scale of Quality of Life (QoL) [16], assessing the child’s autonomy, behaviour, learning abilities, social relationships and overall QoL for the child; and (iv) a Behaviour Questionnaire [17]. This 21-item questionnaire assessed three aspects of behaviour: hyperactivity/attention, anxiety/ depression and sociability. Statistical analyses were performed with SAS software [18]. This study used chi-square and Fisher exact tests for comparison of proportions, Student’s t-test for comparison of means and Pearson correlations. Partial scores were generated by adding up the number of ‘yes’ answers. Questionnaires (see Appendix).
Results Medical data Table I gives a summary of medical information. For the 18 adolescents, mean age at the time of the study was 15 years (range ¼ 12–17 years) and mean age at surgery was 6.8 years (range ¼ 2.3–10.8 years). Mean time-lapse since surgery was 7.8 years (range ¼ 2.2–13.3 years). Pre-operative hydrocephalus was generally present (83%) and was treated by shunt before surgery in seven patients. Complete tumour resection was achieved in 15 (83%) of the 18 patients and incomplete in three. In these three patients, the residual tumour was immediately removed by secondary surgery without any adjuvant treatment. Tumour relapse occurred twice in one patient, respectively 1 year and 2.3 years after initial diagnosis; the recurrent tumour was totally removed by the last surgery. Post-operative complications were present in four patients and included focal neurological symptoms in one case, ataxia in one case and infections (i.e. meningitis,
Pilocytic astrocytoma outcome
DOI: 10.3109/02699052.2014.975281
encephalitis) in two cases. Post-operative shunt insertion was necessary in three cases. General questionnaire (Table I) At the time of the study, 15 patients were following a normal academic curriculum and two were in special classes. Schooling was quasi absent for one patient whose family belonged to the travelling people community. Five patients had a history of school grade repetition once and one patient twice. Eight patients were at the age to sit the middle-school national diploma (‘Brevet des Colle`ges’) and only one failed; this success rate (87.5%) is slightly above the national pass rate (83%) (data from the French Ministry of Education) [19]. The frequency of reported rehabilitation was not significantly different between patients and controls.
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Parental assessment (Table III) This questionnaire was completed by the mother (67%) or both parents (28%) and rarely by the father alone (6%). The child’s illness was known to the school staff, except for three children. A vast majority of parents (87.5%) were satisfied with the medical care and information received about their child’s illness and also with the educational institution and the rehabilitation programme. Fifty-nine per cent of the parents indicated current learning difficulties in the patient group vs. 13% in controls (p ¼ 0.001). Specific difficulties for mathematics tended to be more frequent in patients than in controls (p ¼ 0.09). Scores for Depression/Anxiety and hyperactivity/ disruptive behaviour were marginally higher in patients than in controls (p ¼ 0.04 and 0.05, respectively). No significant difference was found on the Global Evaluation Scale of Quality-of-Life.
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Self-report of long-term difficulties Table II presents a summary of self-reported learning difficulties among study adolescents and healthy controls. Significant differences between patients and controls were observed for almost all items related to subtle neurological deficits arising from cerebellar dysfunction: the patient group reported more difficulties than the control group for balance (p ¼ 0.005), writing (p ¼ 0.001), oral speech (p ¼ 0.01) and fine manual skills (p ¼ 0.01). The differences did not reach significance for the cognitive items, despite a clear tendency among the patients to report more difficulties, especially in mathematics.
Learning difficulties in relation to the medical data School grade repetition was associated with early age at first surgery (p ¼ 0.003), post-operative complications (p ¼ 0.01) and post-operative shunt insertion (p ¼ 0.01). Post-operative shunt insertion was also associated with more frequent difficulties in sports (p ¼ 0.04) and early age at surgery was related to difficulties in mathematics (p ¼ 0.04) and marginally to speech difficulties (p ¼ 0.08). No other significant associations were found.
Study 2: Adults Methods Participants
Table I. Adolescent patient characteristics. Adolescent group (n ¼ 18) Age at time of study, mean (SD) [range] Mean age at onset of symptoms, mean (SD) [range] Mean age at surgery, mean (SD) [range] Time-lapse from surgery, mean (SD) [range] Gender: male, n (%) Medical data Pre-operative hydrocephalus, n (%) Complete excision of tumour, n (%) Tumour recurrence, n (%) VP shunt, n (%) Post-operative complications, n (%) Socio-demographic data (% yes) Father high school diploma Mother high school diploma Educational history, n (%) School repeat years Presence of everyday difficulties, n (%) Rehabilitation, n (%)a Psychotherapy Academic support Speech therapy Occupational therapy Physiotherapy Psychomotor therapyb Other rehabilitation a
15.1 (1.8) [12–17] 6.5 (3.4) [0.4–13.9] 6.8 (2.7) [2.3–10.8] 7.8 (2.9) [2.2–13.3] 6 (33) 14 15 3 3 4
(82) (83) (16) (17) (22)
9 (50) 6 (33)
Table II. Scores for self-reported neurological, cognitive and academic difficulties in astrocytoma adolescents and control group.
6 (33) 5 (29) 5 5 8 2 5 3 3
(29) (29) (47) (12) (29) (18) (18)
At least one rehabilitation. In France, as in other European countries, there are ‘psychomotricians’ for children or adults with neurological or psychiatric disorders who propose different activities (games, etc.) to improve the psychological condition of the patient.
b
Inclusion criteria were (1) surgically treated cerebellar astrocytoma during childhood at the Paediatric Neurosurgery Department of Necker Enfants Malades Hospital in Paris and (2) being aged over 18 years in the year of the present study. Sixty-eight adults corresponded to these criteria. Before the phone interview, the consulting neurologist and one of the authors (FL) sent these patients an envelope containing an explanatory letter and an informed consent form. Forty-six responses were received. In 15 cases contact failed (unknown address). Seven patients refused to participate; according to the medical files, none of them
Patients (n ¼ 18)
Controls (n ¼ 17)
Scores
M
SD
M
SD
p
Reading Mathematics Memory Attention Slowness Writing Talking or expressing oneself Manual skills Balance Sports
2.3 3.2 1.5 0.5 0.8 0.9 1.5 1.5 1.5 1.8
1.9 3.5 1.5 0.5 0.5 0.9 1.3 1.4 1.3 1.2
1.6 1.4 0.8 0.3 0.5 0.1 0.5 0.3 0.4 2.5
1.5 1.9 1.3 0.5 0.6 0.2 0.8 0.5 0.6 1.0
0.24 0.07 0.14 0.39 0.22 0.001 0.01 0.005 0.005 0.08
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Table III. Parent reports of adolescents’ learning difficulties.
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Difficulties (% yes)
Patients’ parents (n ¼ 17)
Learning difficulties Slowness Attention Memory Language Academic Mathematics French Global Evaluation Scale of QoL, mean (SD) Autonomy problems (1–5)a Behavioural problems (1–5)a Learning difficulties (1–5)a Social relationship (1–5)a QoL (1–5)a Total score (5–25) Behavioural Questionnaire: mean (SD) Depression/Anxiety Hyperactivity/Disruptive Behaviour Sociability
Controls’ parents (n ¼ 15)
p
58.8 29.4 29.4 17.6 0
13.3 6.7 6.7 0 0
0.001 0.18 0.18 0.23 1
35.3 23.5
6.7 13.3
0.09 0.65
3.9 3.6 3.7 3.7 4.2 19.1
(0.5) (0.8) (0.8) (0.7) (0.7) (2.5)
3.9 (2.8) 4.1 (3.8) 9.4 (1.4)
4.1 3.8 3.5 4.1 4.3 19.7
(0.6) (0.6) (0.8) (0.8) (0.6) (2.7)
0.34 0.57 0.53 0.15 0.70 0.53
2.0 (1.8) 1.9 (1.9) 9.4 (2.1)
0.04 0.05 0.99
a
1 ¼ a lot of problems. . . 5 ¼ better than most children of the same age.
presented major difficulties compromising their autonomy. There were no controls for the adult group, but figures concerning schooling history were compared to national figures. Material Medical data. From the medical files, information was
gathered about the history of the illness (i.e. age at diagnosis, age at surgery), type of surgery, presence of hydrocephalus, recurrence and secondary surgery and post-operative complications. After receiving the written informed consent of the patients, the interview was performed by telephone. The interview included the following topics: (1) rehabilitation and other therapies; (2) neurological symptoms (related to cerebellar dysfunction, pyramidal syndrome, brain stem syndrome, hydrocephalus, epilepsy); (3) cognitive difficulties and academic and professional achievement (reading, calculation, attention, memory, academic history, highest diploma obtained, professional situation); (4) functional independence (e.g. living alone or with the parents, marriage, job); and (5) opinion about treatment. Statistical analyses were performed with SAS software [18]. Chi-square and Fisher exact tests (comparison of proportions) were used.
Semi-structured interview (see Appendix).
Results Medical data The mean age of the 46 patients at the time of the study was 23.6 years (range ¼ 17.7–29.5 years) and mean age at surgery was 8.5 years (range ¼ 0.7–16. 7 years). The mean follow-up time was 12.9 years (range ¼ 3.2–18.8 years) (Table IV). In 40 patients (86%), the excision was total, according to surgical records. In all cases the tumour was histologically confirmed to be a cerebellar pilocytic astrocytoma. Brain stem involvement was present in three patients
(6.5%). Severe post-operative complications (infectious or haemorrhagic) were present in three cases (6.5%) and postoperative mutism in three cases (6.5%). Among the 46 participants, five patients formed a specific group: they were attending special institutions and had a permanent, severe disability. For these five patients, the phone interview was not possible because of considerable difficulties in understanding and answering the questions. Brain stem involvement (3/5), serious post-operative complications (3/5) and post-operative mutism (3/5) were significantly more frequent in this group of five patients than in the other 41 patients (0/41, p50.001 Fisher exact test). General questionnaire Among the 41 (89%) participants in the phone interview, 14 (34%) were professionally active, 23 (56%) were students and four (10%) were unemployed. Twelve (29%) were financially independent and had their own housing. Concerning rehabilitation and remediation, remedial teaching (39%) and speech therapy (34%) were the most frequent. Seventy-five per cent were satisfied with the outcome of treatment. Nine mentioned the inadequacy of the information they received, because the medical staff communicated solely with their parents. Concerning schooling history, 30 patients (73%) succeeded in the middle-school national diploma (‘Brevet des Colle`ges’), which is close to the national pass rate (83%) (data from the French Ministry of Education). Frequency of school grade repetition once (27%) or twice (29%) among the 41 patients should be compared with the national figures: 36.5% and 7.1% respectively, according to the PISA study [20] (Programme for International Student Assessment), showing that a second school grade repetition was more frequent among patients. Questionnaire about neurological, cognitive and academic difficulties In Table V, the items in the interview are sorted by frequency of reported difficulties in the total sample. Twenty-seven
Pilocytic astrocytoma outcome
DOI: 10.3109/02699052.2014.975281
Table IV. Adult patient characteristics.
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Adult group (n ¼ 46) Age at time of study, mean (SD) [range] Mean age at onset of symptoms, mean (SD) [range] Mean age at surgery, mean (SD) [range] Time-lapse from surgery, mean (SD) [range] Gender: male, n (%) Pre-operative hydrocephalus, n (%) Complete excision of tumour, n (%) Tumour recurrence, n (%) Brain stem involvement, n (%) Post-operative complications, n (%) Post-operative cerebellar mutism, n (%) Rehabilitation (%) Remedial teaching Speech therapy Occupational therapy Physiotherapy Psychomotor therapy Educational/occupational, n (%) Students Workers Looking for a job Sheltered workplace
21.8 (3.3) [18–30] 7.9 (3.7) [0.4–13.4] 8.5 12.9 22 39 40 6 3 16 3
(3.9) [0.7–16.7] (4.7) [3.2–18.8] (48) (85) (86) (13) (6) (35) (6)
16 14 4 9 7
(39) (34) (10) (22) (17)
23 14 4 5
(50) (30) (9) (11)
(66%) of the 41 study patients had difficulties in concentrating (attention deficit). Twenty-six (63%) described memory deficits (such as memorizing a school lesson); half the patients (50%) presented balance difficulties (such as vertigo or difficulties riding a bicycle). Six (14.6%) patients had a change in hand dominance after the surgery.
Discussion A majority of the adolescents reported mild neurological sequelae including slowness, writing difficulties, fine manual skill deficits, balance and speech difficulties. These sequelae are neurological symptoms of cerebellar dysfunction. This is in accordance with Zuzak et al. [6], who observed a high proportion of neurological deficits (43%) in a similar population. In the cognitive-academic dimension, the differences with the control group did not reach statistical significance, despite a tendency for more difficulties in the patient group, such as a clearer tendency to difficulties in mathematics than in reading. These findings are not contradictory with other reports observing impairments in memory, language and attention in long-term survivors of low-grade cerebellar astrocytoma [8, 10, 11]. However, these results recall that, after a cerebellar lesion, the neurological deficits expected are more frequent and more marked than the cognitive deficits. In this study, 83% of the patients had attended a normal schooling. The rate of school grade repetition was almost 3-times higher in patients than in controls (33.3% vs. 12%), but this difference was not statistically significant given the small sample size. The frequency of special education was 11%, which is lower than the 24% rate of special education reported by Aarsen et al. [11]. Parents of study adolescents reported more learning difficulties than parents of healthy controls. Eiser and Morse [21] observed that difficulties appear more marked in
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parental reports than in self-reports in studies assessing difficulties after tumour treatment. However, in the present study, QoL was comparable between patients and controls according to parental report. Zuzak et al. [6] found that, in comparison with healthy controls, patients with cerebellar astrocytoma rated their Health-Related Quality-of-Life similar or even better and they also rated their physical health better than did healthy controls. These authors concluded that long-term neurocognitive and behavioural problems, reported by some of their patients, have only a minimal impact on subjective quality-of-life [6]. In the Behavioural scale, scores for Depression/Anxiety and Hyperactivity/ Disruptive behaviour were higher among patients than among controls. Patients’ parents indicated more often that their child was nervous, anxious, worried, sad or depressed and had temper tantrums or hot temper in comparison to parents of controls. This is in accordance with previous reports of depressive-anxiety problems [6] and affect regulation, impulsivity or irritability difficulties after astrocytoma treatment in childhood [8–10]. Five of the 46 adults (11%) but none of the 18 adolescents presented very poor outcome. This difference, although not statistically significant, might reflect therapeutic improvements in recent years. About 50% of the adults treated for low-grade astrocytoma in childhood reported long-term difficulties associated with neurological sequelae. This is in agreement with Daszkiewicz et al. [14], who found that 60% of a sample of 104 patients presented permanent neurological deficits, usually in the form of balance difficulties and ataxia. Attention and memory deficits were reported by more than half of these patients (respectively, 66% and 63%). The high rate of school grade repetition more than once seems compatible with neuropsychological difficulties described in the literature [8–10, 22]. However, in spite of permanent neurological deficits and reported impairments in attention and memory, the long-term functional outcome of these patients was relatively favourable. The vast majority of patients had a normal academic curriculum and autonomy. The main prognostic factors were post-operative complications, brain stem involvement and post-operative mutism, which were associated with major sequelae and less autonomy. These findings confirm previous reports in the same population [5, 6, 14]. Cerebellar pilocytic astrocytoma is a histologically benign tumour with very good tumour control achieved by surgery alone [6] and very high survival rates [23]. In all the patients in the present study, surgery alone was largely successful in disease control and there were no post-operative deaths. Improved survival rates in paediatric cerebellar tumours have been associated with progress in understanding of the neurophysiological role of the cerebellum, confirming its role not only in the co-ordination of movement but also in the regulation of cognitive and emotional processes and behaviour [24]. Awareness of significant tumour-related and/or therapy-related long-term neurological, cognitive, emotional or behavioural complications has increased [6, 25, 26]. However, studies focusing on the impact of post-operative sequelae on long-term outcome are rare. Few studies have investigated whether the situation of patients treated for pilocytic astrocytoma in childhood is different from that of
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Table V. Adult difficulties reported by phone interview, ordered by frequency.
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Adult group (n ¼ 41)
Remaining attentive during a lesson Memory Balance difficulties Learning lessons Mental calculation Slowness in the execution of a task Written expression Walking easily along the edge of a narrow pavement Learning multiplication tables Understanding the structure of a text Change of dominant hand after the surgery Reading aloud Riding a bicycle Writing fast Answering questions correctly after reading a text
n
%
27 26 20 19 16 14 12 12 11 6 6 6 5 4 4
66 63 50 47 39 34 30 30 28 15 15 15 12 10 10
the general population, nor have they explored the risk factors associated with poor outcomes. Neurological symptoms related to cerebellar dysfunction (e.g. slowness, writing disabilities, speech difficulties, fine manual skill deficits and balance difficulties) were reported both by adolescents and adults. Unlike cognitive complaints, neurological difficulties were significantly more frequent in the adolescents than in the controls. The adolescents’ parents judged the QoL of their child in a similar manner to the controls, but reported more depression/anxiety and hyperactivity/disruptive behaviour. A similar observation was made by Daszkiewicz et al. [14], who also noted that neurological deficits and emotional disorders do not preclude subsequent normal schooling and independent functioning. Specific difficulty in learning to read was not a major problem, as would be expected according to the cerebellar theory of developmental dyslexia [12], and the present study did not clearly show any permanent ‘cerebellar cognitive affective syndrome’ after acquired cerebellar lesions [7, 8]. In adolescents, school grade repetition was associated with young age at surgery. This result is similar to the pattern of long-term cognitive outcome seen in children treated for medulloblastoma [15]. Post-operative complications and recurrence were also associated with school grade repetition in adolescents, in agreement with Pencalet et al. [27]. In adults, serious post-operative complications, brain stem involvement and/or post-operative mutism were associated with major sequelae and lack of autonomy. These findings confirm previous reports on the negative prognosis of brain stem involvement [27–31], post-operative mutism [11, 32] and post-operative infections [27]. Both the present studies highlight the presence of mild fine motor and equilibrium difficulties related to imperfect cerebellar function. Indeed, difficulties in writing, talking, fine manual skills and balance were more often reported in the adolescents treated for pilocytic astrocytoma than in controls and were also frequently reported by the adults. Parents’ reports of learning difficulties were more frequent for patients than for controls and the frequency of self-reported
cognitive difficulties was high among the adults; however, the frequency of self-reported cognitive difficulties was generally not significantly different between patients and controls in the adolescent study. Self-reported cognitive difficulties should be interpreted with caution. Indeed, selfreport does not necessarily correlate with actual learning difficulties. In some cases, patients with a high level of education tend to report more difficulties than patients with low educational level. High educational level might reveal mild cognitive difficulties that may be not apparent in case of low educational status. Despite the tendency for more Depression/Anxiety and Hyperactivity difficulties in patients than in controls in the adolescent study, there was no clear evidence in favour of a permanent ‘affective’ cerebellar syndrome [7]. In particular, sociability was identical in patients and controls in the adolescent study, the frequency of psychotherapy was not significantly different (29% among patients vs. 18% among controls) and there was no clinical evidence of significant psychiatric problems among patient participants. Finally, the cognitive difficulties reported were not specific to reading. Indeed, only 15% of the adults reported reading difficulties and, among adolescents, report of reading difficulties was not significantly higher in patients than in controls. The present study has limitations. No neuropsychological tests were performed, although previous studies have shown that scores on questionnaires (teachers’ report) on learning difficulties in patients treated for cerebellar tumours correlated significantly with IQ scores [33]. The approach was deliberately ecological in order to examine the long-term functional outcome of patients treated for low-grade cerebellar astrocytoma in childhood. The adolescent sample was small, so that the comparisons between patients and controls lacked statistical power. Some patients who corresponded to the inclusion criteria did not participate, but the medical data did not differ between participants and non-participants. The number of patients did not allow a calculation of the reliability of the questionnaire, which needs further studies. Significant differences between patients and controls, despite the small size of the sample, are in favour of the validity of the questions. In conclusion, permanent neurological deficits were reported by both adolescents and adults treated for lowgrade astrocytoma in childhood. These deficits are neurological symptoms of cerebellar dysfunction. Nonetheless, the long-term functional outcome was favourable for the vast majority of patients. Brain stem involvement, post-operative mutism and complications were clearly associated with more negative long-term functional outcomes. Young age at surgery and post-operative complications were associated with school grade repetition. No difference between patients and controls was observed concerning parents’ answers on their child’s QoL, although parents of patients tended to report more learning difficulties, depression/anxiety and hyperactivity/ disruptive behaviour. These findings show that, although most patients are able to lead a close-to-normal life, careful neurological, cognitive and behavioural evaluations after the end of the treatment and at every important step in their school career should contribute to identifying difficulties and to finding the most appropriate solutions.
Pilocytic astrocytoma outcome
DOI: 10.3109/02699052.2014.975281
Acknowledgements We thank the participants for their contribution to this study.
20.
Declaration of interest
21.
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The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. N. Ait Khelifa-Gallois was supported by grants from ‘Canceropoˆle Ile de France’ and ‘Ligue contre le cancer’.
22.
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1. Brain Tumour Foundation of Canada. Juvenile pilocytic astrocytoma. Available online at: http://www.braintumour.ca/4886/ juvenile-pilocytic-astrocytoma-jpa, accessed 9 September 2014. 2. Koeller KK, Rushing EJ. From the archives of the AFIP: Pilocytic astrocytoma: Radiologic-pathologic correlation. Radiographics 2004;24:1693–1708. 3. Dirven CM, Mooij JJ, Molenaar WM. Cerebellar pilocytic astrocytoma: A treatment protocol based upon analysis of 73 cases and a review of the literature. Childs Nervous System 1997;13:17–23. 4. Hojer C, Hildebrandt G, Lanfermann H, Schro¨der R, Haupt WF. Pilocytic astrocytomas of the posterior fossa. A follow-up study in 33 patients. Acta Neurochirurgica (Wien) 1994;129:131–139. 5. Pompili A, Caperle M, Pace A, Ramazzotti V, Raus L, Jandolo B, Occhipinti E. Quality-of-life assessment in patients who had been surgically treated for cerebellar pilocytic astrocytoma in childhood. Journal of Neurosurgery 2002;96:229–234. 6. Zuzak TJ, Poretti A, Drexel B, Zehnder D, Boltshauser E, Grotzer MA. Outcome of children with low-grade cerebellar astrocytoma: Long-term complications and quality of life. Childs Nervous System 2008;24:1447–1455. 7. Schmahmann JD, Sherman JC. The cerebellar cognitive affective syndrome. Brain 1998;121:561–579. 8. Levisohn L, Cronin-Golomb A, Schmahmann JD. Neuropsychological consequences of cerebellar tumour resection in children: Cerebellar cognitive affective syndrome in a paediatric population. Brain 2000;123:1041–1050. 9. Riva D, Giorgi C. The cerebellum contributes to higher functions during development: Evidence from a series of children surgically treated for posterior fossa tumors. Brain 2000;123:1051–1061. 10. Steinlin M, Imfeld S, Zulauf P, Boltshauser E, Lo¨vblad K-O, Ridolfi Lu¨thy A, Perrig W, Kaufmann F. Neuropsychological longterm sequelae after posterior fossa tumour resection during childhood. Brain 2003;126:1998–2008. 11. Aarsen FK, Van Dongen HR, Paquier PF, Van Mourik M, CatsmanBerrevoets CE. Long-term sequelae in children after cerebellar astrocytoma surgery. Neurology 2004;62:1311–1316. 12. Nicolson RI, Fawcett AJ. Automaticity: A new framework for dyslexia research? Cognition 1990;35:159–182. 13. Dennis M, Spiegler BJ, Hetherington CR, Greenberg ML. Neuropsychological sequelae of the treatment of children with medulloblastoma. Journal of Neuro-oncology 1996;29:91–101. 14. Daszkiewicz P, Maryniak A, Roszkowski M, Barszcz S. Long-term functional outcome of surgical treatment of juvenile pilocytic astrocytoma of the cerebellum in children. Childs Nervous System 2009;25:855–860. 15. Grill J, Viguier D, Kieffer V, Bulteau C, Sainte-Rose C, Hartmann O, Kalifa C, Dellatolas G. Critical risk factors for intellectual impairment in children with posterior fossa tumors: The role of cerebellar damage. Journal of Neurosurgery 2004;101:152–158. 16. Soria C, El Sabbagh S, Escolano S, Bobet R, Bulteau C, Dellatolas G. Quality of life in children with epilepsy and cognitive impairment: A review and a pilot study. Developmental Neurorehabilitation 2007;10:213–221. 17. Sabbagh SE, Soria C, Escolano S, Bulteau C, Dellatolas G. Impact of epilepsy characteristics and behavioral problems on school placement in children. Epilepsy Behavior 2006;9:573–578. 18. SAS Institute INC SAS/STAT. User’s guide. Version 6. 4th ed. Vol. 1. Cary, NC: SAS; 1989. 19. ‘‘Diploˆme National Du Brevet, Session 2009.’’ – Ministe`re De L’E´ducation Nationale, De L’Enseignement Supe´rieur Et De La Recherche. N.p., n.d. Web. 09 Sept. 2014. – See more at: http://
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www.education.gouv.fr/cid53600/diplome-national-du-brevet-session-2009.html. ‘‘PISA – OECD – Re´sultats Du PISA 2009.’’ PISA – OECD. Available online at: http://www.oecd.org/pisa/pisaproducts/ 46619703.pdf, accessed 29 March 2014. Eiser C, Morse R. Quality-of-life measures in chronic diseases of childhood. Health Technol Assess 2001;5:1–157. Bebbe DW, Ris MD, Armstrong FD, Fontanesi J, Mulhern R, Holmes E, Wisoff JH. Cognitive and adaptive outcome in lowgrade pediatric cerebellar astrocytomas: Evidence of diminished cognitive and adaptive functioning in National Collaborative Research Studies (CCG 9891/POG 9130). Journal of Clinical Oncology 2005;23:5198–5204. Villarejo F, de Diego JMB, de la Riva AG. Prognosis of cerebellar astrocytomas in children. Childs Nervous System 2008;24:203–210. Jenney ME. Theoretical issues pertinent to measurement of quality of life. Medical & Pediatric Oncology Supplement 1998a;1:41–45. Jenkin D, Danjoux C, Greenberg M. Subsequent quality of life for children irradiated for a brain tumor before age four years. Medical & Pediatric Oncology 1998;31:506–511. Cohen BH, Packer RJ, Siegel KR, Rorke LB, D’Angio G, Sutton LN, Bruce DA, Schut L. Brain tumors in children under 2 years: Treatment, survival and long-term prognosis. Pediatric Neurosurgery 1993;19:171–179. Pencalet P, Maixner W, Sainte-Rose C, Lellouch-Tubiana A, Cinalli G, Zerah M, Pierre-Kahn A, Hoppe-Hirsch E, Bourgeois M, Renier D. Benign cerebellar astrocytomas in children. Journal of Neurosurgery 1999;90:265–273. Geissinger JD. Astrocytomas of the cerebellum in children. Longterm study. Archives of Neurology 1971;24:125–135. Gol A, Mckissock W. The cerebellar astrocytomas: A report on 98 verified cases. Journal of Neurosurgery 1959;16:287–296. Schneider Jr JH, Raffel C, McComb JG. Benign cerebellar astrocytomas of childhood. Neurosurgery 1992;30:58–62; discussion 62–63. Sgouros S, Fineron PW, Hockley AD. Cerebellar astrocytoma of childhood: Long-term follow-up. Childs Nervous System 1995;11: 89–96. Schmahmann JD. Disorders of the cerebellum: Ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. Journal of Neuropsychiatry & Clinical Neuroscience 2004;16:367–378. Kieffer V, Longaud A, Callu D, Laroussinie F, Viguier D, Grill J, Dellatolas G. Teachers’ report of learning and behavioural difficulties in children treated for cerebellar tumors. Brain Injury 2012;26:1014–1020.
Appendix A. Adolescent study 1. The adolescent self-report (a) General questionnaire: Please answer the following questions:
Personal educational history: (1) Are you presently attending school? (Yes/No), (2) What class? (3) Last diploma obtained? (4) School grade repetition? (Yes/No), (5) How many times have you repeated a school grade? (6) Special school? (Yes/No) Rehabilitation (Yes/No): (1) Psychotherapy, (2) Remedial teaching, (3) Speech therapy (4) Occupational therapy, (5) Physiotherapy, (6) Psychomotor therapy, (7) Other rehabilitation. (b) Neurological, cognitive and academic difficulties: Presence of everyday difficulties: (Yes/No) ‘Do you have difficulties in the following areas?’ (Yes/No). Reading difficulties: (1) Learning to read, (2) Reading aloud, (3) Reading silently without saying the words aloud, (4) Reading silently without whispering, (4) Answering questions about a text, (5) Finding information in a text, (6) Moving from one line to another, (7) Enjoying reading, (8) Difficulties reading, (9) Slowness in reading. Difficulties in mathematics: (1) Mathematics in general, (2) Solving additions on paper, (3) Solving subtractions on paper, (4) Multiplications, (5) Divisions, (6) Learning the multiplication tables, (6) Solving problems, (7) Mental calculation, (8) Performing simple calculations without a calculator, (9) Geometry.
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Memory difficulties: (1) Learning a lesson, (2) Remembering what
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has been learned, (3) Visual memory of graphic representations, (4) Learning poems, (5) Memorizing instructions. Attention difficulties: (1) Remaining attentive during a lesson. Slowness: (1) Completing exercises during exams, (2) Taking notes during lessons. Writing difficulties: (1) Writing, (2) Writing fast, (3) Writing legibly. Difficulties talking or expressing yourself: (1) Expressing views orally, (2) Hesitating to use long or complicated words, (3) Speaking as fast as most people, (4) Controlling your voice. Difficulties in manual skills: (1) Manual difficulties, (2) Using a ruler or compass, (3) Performing everyday gestures, (4) Slowness dressing, (5) Slowness housing, (6) Slower gestures than most people, (7) Clumsiness drawing simple things, (8) Reproducing a rhythm by tapping on a surface. Balance difficulties: (1) Balance difficulties in general, (2) Walking on a beam, (3) Walking on the edge of a narrow pavement, (4) Riding a bicycle, (5) Running down stairs Sports practice difficulties: (1) Are you sporty? (2) Do you do a sport now? (3) Do you have difficulties doing sports at school? (4) Do you like sports at school?
2. Parental questionnaire (a) General questionnaire: (1) Questionnaire completed by: the mother, the father, both parents.
(2) Educational level of the parents: (1) father: high school diploma? (2) mother: high school diploma? (‘Baccalaureat’) (Yes/No)
(3) Did you talk about your child’s illness to the school staff? (Yes/No)*
(4) Are you satisfied with: (1) the medical information you received; (2) the educational institution attended by your child; (3) the rehabilitation programmes (Very satisfied/fairly satisfied/Rather dissatisfied/very dissatisfied)*
(b) Questions about present type of school frequented, current learning difficulties:
Does your child have learning difficulties? (Yes/No) What kind of difficulties does he/she have? (Several answers possible): (1) Slowness, (2) Attention, (3) Memory, (4) Language, (4) Difficulties in French (5) Difficulties in mathematics, (6) Behaviour problems at school, (7) Other (please specify). (c) Global Evaluation Scale (Soria et al. [16]).
(d) Behaviour Questionnaire (Sabbagh et al. [17]).
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B. Adult study: Semi-structured telephone interview 1. General questionnaire (Yes/No) Academic and professional achievement: Educational/occupational: Student/Working/Looking for a job/ Sheltered workplace. Personal educational history: (1) school grade repetition? (Yes/No), (2) how many times did you repeat a school grade? (3) what is the highest diploma you obtained? (4) did you pass the Brevet des Colle`ges (middle-school national diploma)? Functional independence: (1) are you financially independent? (2) Where do you live (several answers possible): with your parents/ alone/with a partner/other situation? (Specify), (3) do you have a driving license? Rehabilitation: (1) Psychotherapy, (2) Remedial teaching, (3) Speech therapy, (4) Occupational therapy, (5) Physiotherapy, (6) Psychomotor therapy, (7) Other rehabilitation. Satisfaction with the medical information received: (Very satisfied/ Fairly satisfied/Rather dissatisfied/very dissatisfied)
2. Questionnaire about neurological, cognitive and academic difficulties: ‘Do/did you have difficulties in the following areas’ (Yes/No): Attention: (1) sustaining attention during a lesson? (2) Are you easily distracted? Memory: (1) learning a lesson? (2) remembering a lesson? (3) learning the multiplication tables? (4) learning a poem? (5) memorizing a plan or a figure? (6) remembering an instruction? Balance: (1) do you have any balance difficulties? (2) walking on a beam, (3) walking on the edge of a narrow pavement, (4) riding a bicycle, (5) running down stairs? Mental calculation: do you have difficulty doing additions? subtractions? multiplications? divisions? in problem-solving? Slowness: are you slow completing a task? Do you have difficulty finishing a task in a given time? Manual skills and writing: (1) do you have difficulty using a ruler? (2) using scissors, (3) did you change your dominant hand after surgery? (4) do you have difficulty writing? (5) writing fast? (6) is your handwriting legible? (7) do you get cramp when writing? (8) do you use a computer? Language and reading difficulties: (1) do you have difficulties in written expression?, understanding the structure of a text? (2) can you easily answer questions correctly after reading a text? (3) do you have difficulties reading aloud?
ORIGINAL ARTICLE
Long-term functional outcome of patients with cerebellar pilocytic astrocytoma surgically treated in childhood N. Ait Khelifa-Gallois1, F. Laroussinie1, S. Puget2, C. Sainte- Rose2, & G. Dellatolas1 INSERM U669, Univ Paris Sud, Univ Paris Descartes, Paris, France and 2Pediatric Neurosurgery Department, Necker Enfants Malades Hospital, Paris, France
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Abstract
Keywords
Purpose: A number of studies report neurological and cognitive deficits and behavioural disorders in children after surgical treatment for a benign cerebellar tumour. The present study explores functional outcome in adolescents and adults treated for a low-grade cerebellar astrocytoma in childhood. Materials and methods: Participants were 18 adolescents and 46 adults treated for low-grade astrocytoma in childhood. Academic achievement, professional status and neurological, cognitive and behavioural disturbances were collected using self-completed and parental questionnaires for adolescents and phone interview for adults. For the adolescent group, a control group filled in the same questionnaires. Results: Mean time lapse from surgery was 7.8 years for adolescents and 12.9 years for adults. Five adults (11%) had major sequelae related to post-operative complications, post-operative mutism and/or brain stem involvement. All the other participants presented close-to-normal academic achievement and normal autonomy, despite a high rate of reported cognitive difficulties and difficulties related to mild neurological sequelae (fine motor skills, balance). Conclusion: The long-term functional outcome of low-grade cerebellar astrocytoma is generally favourable, in the absence of post-operative complications and brain stem involvement. No major impact of neurological deficits, cognitive problems and emotional disorders on academic achievement and independent functioning was observed.
Cognitive difficulties, learning difficulties, long-term functional outcome, low-grade cerebellar astrocytoma, neurological sequelae, QoL
Introduction Pilocytic astrocytoma has an overall incidence of 0.37 per 100 000 persons per year [1] and a high survival rate—94% at 10 years—which is by far the best for any glial tumour [2]. After surgery, the tumour does not generally recur, although careful evaluation with neuroimaging is recommended in the years following surgery [3, 4]. Patients surgically treated for these tumours are generally considered to be cured [5]. However, despite their benign biological nature, an increasing number of studies have reported that low-grade cerebellar astrocytomas can cause not only permanent neurological symptoms related to cerebellar dysfunction (e.g. ataxia, dysmetria, nystagmus, dysarthria) [6], but also cognitive deficits. Schmahmann and Sherman [7] described a ‘cerebellar cognitive affective syndrome’ in adults with acquired cerebellar lesions, which is characterized by deficits in executive functions, linguistic processing, spatial cognition and affect regulation. Impairments in planning and sequencing, visual–spatial functions, expressive language, verbal memory, verbal fluency, attention, processing speed and
Correspondence: Nadira Ait Khelifa-Gallois, INSERM U669, 16 avenue Paul Vaillant Couturier, 94807, Villejuif, France. Tel: 0145595392. Fax: 0145595331. E-mail: [email protected]
History Received 2 May 2014 Revised 11 September 2014 Accepted 7 October 2014 Published online 5 November 2014
regulation of affect have been described in patients who underwent resection of a cerebellar tumour in childhood without additional therapy [8–10]. Likewise, behavioural deficits, impairments in interpersonal relationships, and academic difficulties have been reported in survivors of childhood low-grade astrocytoma [10, 11]. In addition, specific difficulty in learning to read has been attributed to cerebellar dysfunction [12]. Reports that cerebellar lesions produce intellectual and behavioural deficits make it important to determine the outcome of children with low-grade astrocytoma and the impact of the neurological, cognitive and behavioural difficulties described on long-term academic achievement, autonomy and quality-of-life. In fact, little is known about the long-term outcome after resection of a low-grade cerebellar astrocytoma. The impairments in intelligence, memory, language, attention, academic skills and psychosocial function that have been reported [13] have been frequently observed in groups that have undergone not only cerebellar resection but also cranial irradiation and/or chemotherapy [8]. Additionally, it can be remarked that the questionnaires used in studies that evaluate long-term outcome of low-grade cerebellar astrocytoma were developed to evaluate sequelae in brain tumours in general [5, 6]. A few studies used questionnaires to assess long-term outcome. Pompili et al. [5] used a questionnaire to assess the
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quality-of-life (QoL) of adults surgically treated for cerebellar pilocytic astrocytoma in childhood and concluded that, by traditional standards, these patients appear to fare quite well. Nevertheless, their self-reported life experience was less satisfactory than that of the control group. These authors emphasized the role of psychosocial factors in complete recovery and good quality-of-life. Daszkiewicz et al. [14] observed that the long-term functional outcome of juvenile cerebellar pilocytic astrocytoma was relatively favourable, in spite of permanent neurological deficits and emotional disorders in over half of the patients. These did not, however, preclude normal education and independent functioning. Finally, Zuzak et al. [6] concluded that children treated for low-grade cerebellar astrocytomas have a low risk of neurological, cognitive, emotional and behavioural complications when compared with other paediatric brain tumours and that their quality-of-life was similar to that of healthy controls. The present study used questionnaires and phone interviews focusing on neurological difficulties classically related to cerebellar dysfunction on one hand and to cognitive and behavioural difficulties as described in the literature after cerebellar damage on the other. In a group of adolescents and adults treated for a low-grade cerebellar astrocytoma, the aims were: (i) to collect self-completed or parental reports of neurological, cognitive and behavioural difficulties; (ii) to examine academic achievement, professional status and autonomy; and (iii) to explore whether negative outcomes, if present, are associated with specific risk factors. The present report includes two studies; the first, in adolescents, used self-completed and parental questionnaires to describe neurological, cognitive and behavioural difficulties and academic situation; and the second, in adults, used a semistructured interview to provide a description of reported difficulties and present life situation.
Study 1: Adolescents Methods Participants Inclusion criteria were: (1) surgically treated cerebellar astrocytoma during childhood at the Paediatric Neurosurgery Department of Necker Enfants Malades Hospital in Paris; (2) being aged 12–18 years in the year of the present study. Twenty-five adolescents corresponded to these criteria. Contact with adolescents and their parents or legal caregivers was made by the consulting physician, who gave or sent the parents an envelope containing an explanatory letter, an informed consent form and two questionnaires, one for the adolescent and the second for the parents. They were asked to return the informed consent and the questionnaires completed. Contact failed for six adolescents (impossible to find the address); four of them were living in countries other than France. One family refused to participate. Eighteen adolescents completed the self-report questionnaire and 17 of their parents completed the parental questionnaire. Information available concerning the non-participants about their present school situation and from the medical files did not show any significant difference between participants
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and non-participants. Seventeen healthy control adolescents recruited in ordinary schools of the same age, gender and parental education level, and 15 of their parents, completed the same questionnaires. Materials Medical data. From the medical files, information was
gathered about the history of the illness (i.e. age at diagnosis, age at surgery), type of surgery, presence of pre-operative hydrocephalus, recurrence of the tumour and secondary surgery and post-operative complications. The adolescent self-report and the parental questionnaire, presented in the Appendix, were developed by the present authors and based on previous experience from clinical investigations in children with brain tumours [15, 16]. The adolescent self-report included (i) a General Questionnaire concerning socio-demographic data, educational history, everyday difficulties and rehabilitation; (ii) a questionnaire about neurological, cognitive and academic difficulties (see Appendix). The parental questionnaire included (i) a General questionnaire concerning sociodemographic data, educational history, whether the school staff were aware of the illness, rehabilitation and satisfaction with the medical care received and rehabilitation; (ii) questions about present type of school frequented, current learning difficulties (i.e. slowness, attention, memory, language, academic or behavioural difficulties); (iii) the Global Evaluation Scale of Quality of Life (QoL) [16], assessing the child’s autonomy, behaviour, learning abilities, social relationships and overall QoL for the child; and (iv) a Behaviour Questionnaire [17]. This 21-item questionnaire assessed three aspects of behaviour: hyperactivity/attention, anxiety/ depression and sociability. Statistical analyses were performed with SAS software [18]. This study used chi-square and Fisher exact tests for comparison of proportions, Student’s t-test for comparison of means and Pearson correlations. Partial scores were generated by adding up the number of ‘yes’ answers. Questionnaires (see Appendix).
Results Medical data Table I gives a summary of medical information. For the 18 adolescents, mean age at the time of the study was 15 years (range ¼ 12–17 years) and mean age at surgery was 6.8 years (range ¼ 2.3–10.8 years). Mean time-lapse since surgery was 7.8 years (range ¼ 2.2–13.3 years). Pre-operative hydrocephalus was generally present (83%) and was treated by shunt before surgery in seven patients. Complete tumour resection was achieved in 15 (83%) of the 18 patients and incomplete in three. In these three patients, the residual tumour was immediately removed by secondary surgery without any adjuvant treatment. Tumour relapse occurred twice in one patient, respectively 1 year and 2.3 years after initial diagnosis; the recurrent tumour was totally removed by the last surgery. Post-operative complications were present in four patients and included focal neurological symptoms in one case, ataxia in one case and infections (i.e. meningitis,
Pilocytic astrocytoma outcome
DOI: 10.3109/02699052.2014.975281
encephalitis) in two cases. Post-operative shunt insertion was necessary in three cases. General questionnaire (Table I) At the time of the study, 15 patients were following a normal academic curriculum and two were in special classes. Schooling was quasi absent for one patient whose family belonged to the travelling people community. Five patients had a history of school grade repetition once and one patient twice. Eight patients were at the age to sit the middle-school national diploma (‘Brevet des Colle`ges’) and only one failed; this success rate (87.5%) is slightly above the national pass rate (83%) (data from the French Ministry of Education) [19]. The frequency of reported rehabilitation was not significantly different between patients and controls.
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Parental assessment (Table III) This questionnaire was completed by the mother (67%) or both parents (28%) and rarely by the father alone (6%). The child’s illness was known to the school staff, except for three children. A vast majority of parents (87.5%) were satisfied with the medical care and information received about their child’s illness and also with the educational institution and the rehabilitation programme. Fifty-nine per cent of the parents indicated current learning difficulties in the patient group vs. 13% in controls (p ¼ 0.001). Specific difficulties for mathematics tended to be more frequent in patients than in controls (p ¼ 0.09). Scores for Depression/Anxiety and hyperactivity/ disruptive behaviour were marginally higher in patients than in controls (p ¼ 0.04 and 0.05, respectively). No significant difference was found on the Global Evaluation Scale of Quality-of-Life.
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Self-report of long-term difficulties Table II presents a summary of self-reported learning difficulties among study adolescents and healthy controls. Significant differences between patients and controls were observed for almost all items related to subtle neurological deficits arising from cerebellar dysfunction: the patient group reported more difficulties than the control group for balance (p ¼ 0.005), writing (p ¼ 0.001), oral speech (p ¼ 0.01) and fine manual skills (p ¼ 0.01). The differences did not reach significance for the cognitive items, despite a clear tendency among the patients to report more difficulties, especially in mathematics.
Learning difficulties in relation to the medical data School grade repetition was associated with early age at first surgery (p ¼ 0.003), post-operative complications (p ¼ 0.01) and post-operative shunt insertion (p ¼ 0.01). Post-operative shunt insertion was also associated with more frequent difficulties in sports (p ¼ 0.04) and early age at surgery was related to difficulties in mathematics (p ¼ 0.04) and marginally to speech difficulties (p ¼ 0.08). No other significant associations were found.
Study 2: Adults Methods Participants
Table I. Adolescent patient characteristics. Adolescent group (n ¼ 18) Age at time of study, mean (SD) [range] Mean age at onset of symptoms, mean (SD) [range] Mean age at surgery, mean (SD) [range] Time-lapse from surgery, mean (SD) [range] Gender: male, n (%) Medical data Pre-operative hydrocephalus, n (%) Complete excision of tumour, n (%) Tumour recurrence, n (%) VP shunt, n (%) Post-operative complications, n (%) Socio-demographic data (% yes) Father high school diploma Mother high school diploma Educational history, n (%) School repeat years Presence of everyday difficulties, n (%) Rehabilitation, n (%)a Psychotherapy Academic support Speech therapy Occupational therapy Physiotherapy Psychomotor therapyb Other rehabilitation a
15.1 (1.8) [12–17] 6.5 (3.4) [0.4–13.9] 6.8 (2.7) [2.3–10.8] 7.8 (2.9) [2.2–13.3] 6 (33) 14 15 3 3 4
(82) (83) (16) (17) (22)
9 (50) 6 (33)
Table II. Scores for self-reported neurological, cognitive and academic difficulties in astrocytoma adolescents and control group.
6 (33) 5 (29) 5 5 8 2 5 3 3
(29) (29) (47) (12) (29) (18) (18)
At least one rehabilitation. In France, as in other European countries, there are ‘psychomotricians’ for children or adults with neurological or psychiatric disorders who propose different activities (games, etc.) to improve the psychological condition of the patient.
b
Inclusion criteria were (1) surgically treated cerebellar astrocytoma during childhood at the Paediatric Neurosurgery Department of Necker Enfants Malades Hospital in Paris and (2) being aged over 18 years in the year of the present study. Sixty-eight adults corresponded to these criteria. Before the phone interview, the consulting neurologist and one of the authors (FL) sent these patients an envelope containing an explanatory letter and an informed consent form. Forty-six responses were received. In 15 cases contact failed (unknown address). Seven patients refused to participate; according to the medical files, none of them
Patients (n ¼ 18)
Controls (n ¼ 17)
Scores
M
SD
M
SD
p
Reading Mathematics Memory Attention Slowness Writing Talking or expressing oneself Manual skills Balance Sports
2.3 3.2 1.5 0.5 0.8 0.9 1.5 1.5 1.5 1.8
1.9 3.5 1.5 0.5 0.5 0.9 1.3 1.4 1.3 1.2
1.6 1.4 0.8 0.3 0.5 0.1 0.5 0.3 0.4 2.5
1.5 1.9 1.3 0.5 0.6 0.2 0.8 0.5 0.6 1.0
0.24 0.07 0.14 0.39 0.22 0.001 0.01 0.005 0.005 0.08
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Table III. Parent reports of adolescents’ learning difficulties.
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Difficulties (% yes)
Patients’ parents (n ¼ 17)
Learning difficulties Slowness Attention Memory Language Academic Mathematics French Global Evaluation Scale of QoL, mean (SD) Autonomy problems (1–5)a Behavioural problems (1–5)a Learning difficulties (1–5)a Social relationship (1–5)a QoL (1–5)a Total score (5–25) Behavioural Questionnaire: mean (SD) Depression/Anxiety Hyperactivity/Disruptive Behaviour Sociability
Controls’ parents (n ¼ 15)
p
58.8 29.4 29.4 17.6 0
13.3 6.7 6.7 0 0
0.001 0.18 0.18 0.23 1
35.3 23.5
6.7 13.3
0.09 0.65
3.9 3.6 3.7 3.7 4.2 19.1
(0.5) (0.8) (0.8) (0.7) (0.7) (2.5)
3.9 (2.8) 4.1 (3.8) 9.4 (1.4)
4.1 3.8 3.5 4.1 4.3 19.7
(0.6) (0.6) (0.8) (0.8) (0.6) (2.7)
0.34 0.57 0.53 0.15 0.70 0.53
2.0 (1.8) 1.9 (1.9) 9.4 (2.1)
0.04 0.05 0.99
a
1 ¼ a lot of problems. . . 5 ¼ better than most children of the same age.
presented major difficulties compromising their autonomy. There were no controls for the adult group, but figures concerning schooling history were compared to national figures. Material Medical data. From the medical files, information was
gathered about the history of the illness (i.e. age at diagnosis, age at surgery), type of surgery, presence of hydrocephalus, recurrence and secondary surgery and post-operative complications. After receiving the written informed consent of the patients, the interview was performed by telephone. The interview included the following topics: (1) rehabilitation and other therapies; (2) neurological symptoms (related to cerebellar dysfunction, pyramidal syndrome, brain stem syndrome, hydrocephalus, epilepsy); (3) cognitive difficulties and academic and professional achievement (reading, calculation, attention, memory, academic history, highest diploma obtained, professional situation); (4) functional independence (e.g. living alone or with the parents, marriage, job); and (5) opinion about treatment. Statistical analyses were performed with SAS software [18]. Chi-square and Fisher exact tests (comparison of proportions) were used.
Semi-structured interview (see Appendix).
Results Medical data The mean age of the 46 patients at the time of the study was 23.6 years (range ¼ 17.7–29.5 years) and mean age at surgery was 8.5 years (range ¼ 0.7–16. 7 years). The mean follow-up time was 12.9 years (range ¼ 3.2–18.8 years) (Table IV). In 40 patients (86%), the excision was total, according to surgical records. In all cases the tumour was histologically confirmed to be a cerebellar pilocytic astrocytoma. Brain stem involvement was present in three patients
(6.5%). Severe post-operative complications (infectious or haemorrhagic) were present in three cases (6.5%) and postoperative mutism in three cases (6.5%). Among the 46 participants, five patients formed a specific group: they were attending special institutions and had a permanent, severe disability. For these five patients, the phone interview was not possible because of considerable difficulties in understanding and answering the questions. Brain stem involvement (3/5), serious post-operative complications (3/5) and post-operative mutism (3/5) were significantly more frequent in this group of five patients than in the other 41 patients (0/41, p50.001 Fisher exact test). General questionnaire Among the 41 (89%) participants in the phone interview, 14 (34%) were professionally active, 23 (56%) were students and four (10%) were unemployed. Twelve (29%) were financially independent and had their own housing. Concerning rehabilitation and remediation, remedial teaching (39%) and speech therapy (34%) were the most frequent. Seventy-five per cent were satisfied with the outcome of treatment. Nine mentioned the inadequacy of the information they received, because the medical staff communicated solely with their parents. Concerning schooling history, 30 patients (73%) succeeded in the middle-school national diploma (‘Brevet des Colle`ges’), which is close to the national pass rate (83%) (data from the French Ministry of Education). Frequency of school grade repetition once (27%) or twice (29%) among the 41 patients should be compared with the national figures: 36.5% and 7.1% respectively, according to the PISA study [20] (Programme for International Student Assessment), showing that a second school grade repetition was more frequent among patients. Questionnaire about neurological, cognitive and academic difficulties In Table V, the items in the interview are sorted by frequency of reported difficulties in the total sample. Twenty-seven
Pilocytic astrocytoma outcome
DOI: 10.3109/02699052.2014.975281
Table IV. Adult patient characteristics.
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Adult group (n ¼ 46) Age at time of study, mean (SD) [range] Mean age at onset of symptoms, mean (SD) [range] Mean age at surgery, mean (SD) [range] Time-lapse from surgery, mean (SD) [range] Gender: male, n (%) Pre-operative hydrocephalus, n (%) Complete excision of tumour, n (%) Tumour recurrence, n (%) Brain stem involvement, n (%) Post-operative complications, n (%) Post-operative cerebellar mutism, n (%) Rehabilitation (%) Remedial teaching Speech therapy Occupational therapy Physiotherapy Psychomotor therapy Educational/occupational, n (%) Students Workers Looking for a job Sheltered workplace
21.8 (3.3) [18–30] 7.9 (3.7) [0.4–13.4] 8.5 12.9 22 39 40 6 3 16 3
(3.9) [0.7–16.7] (4.7) [3.2–18.8] (48) (85) (86) (13) (6) (35) (6)
16 14 4 9 7
(39) (34) (10) (22) (17)
23 14 4 5
(50) (30) (9) (11)
(66%) of the 41 study patients had difficulties in concentrating (attention deficit). Twenty-six (63%) described memory deficits (such as memorizing a school lesson); half the patients (50%) presented balance difficulties (such as vertigo or difficulties riding a bicycle). Six (14.6%) patients had a change in hand dominance after the surgery.
Discussion A majority of the adolescents reported mild neurological sequelae including slowness, writing difficulties, fine manual skill deficits, balance and speech difficulties. These sequelae are neurological symptoms of cerebellar dysfunction. This is in accordance with Zuzak et al. [6], who observed a high proportion of neurological deficits (43%) in a similar population. In the cognitive-academic dimension, the differences with the control group did not reach statistical significance, despite a tendency for more difficulties in the patient group, such as a clearer tendency to difficulties in mathematics than in reading. These findings are not contradictory with other reports observing impairments in memory, language and attention in long-term survivors of low-grade cerebellar astrocytoma [8, 10, 11]. However, these results recall that, after a cerebellar lesion, the neurological deficits expected are more frequent and more marked than the cognitive deficits. In this study, 83% of the patients had attended a normal schooling. The rate of school grade repetition was almost 3-times higher in patients than in controls (33.3% vs. 12%), but this difference was not statistically significant given the small sample size. The frequency of special education was 11%, which is lower than the 24% rate of special education reported by Aarsen et al. [11]. Parents of study adolescents reported more learning difficulties than parents of healthy controls. Eiser and Morse [21] observed that difficulties appear more marked in
5
parental reports than in self-reports in studies assessing difficulties after tumour treatment. However, in the present study, QoL was comparable between patients and controls according to parental report. Zuzak et al. [6] found that, in comparison with healthy controls, patients with cerebellar astrocytoma rated their Health-Related Quality-of-Life similar or even better and they also rated their physical health better than did healthy controls. These authors concluded that long-term neurocognitive and behavioural problems, reported by some of their patients, have only a minimal impact on subjective quality-of-life [6]. In the Behavioural scale, scores for Depression/Anxiety and Hyperactivity/ Disruptive behaviour were higher among patients than among controls. Patients’ parents indicated more often that their child was nervous, anxious, worried, sad or depressed and had temper tantrums or hot temper in comparison to parents of controls. This is in accordance with previous reports of depressive-anxiety problems [6] and affect regulation, impulsivity or irritability difficulties after astrocytoma treatment in childhood [8–10]. Five of the 46 adults (11%) but none of the 18 adolescents presented very poor outcome. This difference, although not statistically significant, might reflect therapeutic improvements in recent years. About 50% of the adults treated for low-grade astrocytoma in childhood reported long-term difficulties associated with neurological sequelae. This is in agreement with Daszkiewicz et al. [14], who found that 60% of a sample of 104 patients presented permanent neurological deficits, usually in the form of balance difficulties and ataxia. Attention and memory deficits were reported by more than half of these patients (respectively, 66% and 63%). The high rate of school grade repetition more than once seems compatible with neuropsychological difficulties described in the literature [8–10, 22]. However, in spite of permanent neurological deficits and reported impairments in attention and memory, the long-term functional outcome of these patients was relatively favourable. The vast majority of patients had a normal academic curriculum and autonomy. The main prognostic factors were post-operative complications, brain stem involvement and post-operative mutism, which were associated with major sequelae and less autonomy. These findings confirm previous reports in the same population [5, 6, 14]. Cerebellar pilocytic astrocytoma is a histologically benign tumour with very good tumour control achieved by surgery alone [6] and very high survival rates [23]. In all the patients in the present study, surgery alone was largely successful in disease control and there were no post-operative deaths. Improved survival rates in paediatric cerebellar tumours have been associated with progress in understanding of the neurophysiological role of the cerebellum, confirming its role not only in the co-ordination of movement but also in the regulation of cognitive and emotional processes and behaviour [24]. Awareness of significant tumour-related and/or therapy-related long-term neurological, cognitive, emotional or behavioural complications has increased [6, 25, 26]. However, studies focusing on the impact of post-operative sequelae on long-term outcome are rare. Few studies have investigated whether the situation of patients treated for pilocytic astrocytoma in childhood is different from that of
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Table V. Adult difficulties reported by phone interview, ordered by frequency.
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Adult group (n ¼ 41)
Remaining attentive during a lesson Memory Balance difficulties Learning lessons Mental calculation Slowness in the execution of a task Written expression Walking easily along the edge of a narrow pavement Learning multiplication tables Understanding the structure of a text Change of dominant hand after the surgery Reading aloud Riding a bicycle Writing fast Answering questions correctly after reading a text
n
%
27 26 20 19 16 14 12 12 11 6 6 6 5 4 4
66 63 50 47 39 34 30 30 28 15 15 15 12 10 10
the general population, nor have they explored the risk factors associated with poor outcomes. Neurological symptoms related to cerebellar dysfunction (e.g. slowness, writing disabilities, speech difficulties, fine manual skill deficits and balance difficulties) were reported both by adolescents and adults. Unlike cognitive complaints, neurological difficulties were significantly more frequent in the adolescents than in the controls. The adolescents’ parents judged the QoL of their child in a similar manner to the controls, but reported more depression/anxiety and hyperactivity/disruptive behaviour. A similar observation was made by Daszkiewicz et al. [14], who also noted that neurological deficits and emotional disorders do not preclude subsequent normal schooling and independent functioning. Specific difficulty in learning to read was not a major problem, as would be expected according to the cerebellar theory of developmental dyslexia [12], and the present study did not clearly show any permanent ‘cerebellar cognitive affective syndrome’ after acquired cerebellar lesions [7, 8]. In adolescents, school grade repetition was associated with young age at surgery. This result is similar to the pattern of long-term cognitive outcome seen in children treated for medulloblastoma [15]. Post-operative complications and recurrence were also associated with school grade repetition in adolescents, in agreement with Pencalet et al. [27]. In adults, serious post-operative complications, brain stem involvement and/or post-operative mutism were associated with major sequelae and lack of autonomy. These findings confirm previous reports on the negative prognosis of brain stem involvement [27–31], post-operative mutism [11, 32] and post-operative infections [27]. Both the present studies highlight the presence of mild fine motor and equilibrium difficulties related to imperfect cerebellar function. Indeed, difficulties in writing, talking, fine manual skills and balance were more often reported in the adolescents treated for pilocytic astrocytoma than in controls and were also frequently reported by the adults. Parents’ reports of learning difficulties were more frequent for patients than for controls and the frequency of self-reported
cognitive difficulties was high among the adults; however, the frequency of self-reported cognitive difficulties was generally not significantly different between patients and controls in the adolescent study. Self-reported cognitive difficulties should be interpreted with caution. Indeed, selfreport does not necessarily correlate with actual learning difficulties. In some cases, patients with a high level of education tend to report more difficulties than patients with low educational level. High educational level might reveal mild cognitive difficulties that may be not apparent in case of low educational status. Despite the tendency for more Depression/Anxiety and Hyperactivity difficulties in patients than in controls in the adolescent study, there was no clear evidence in favour of a permanent ‘affective’ cerebellar syndrome [7]. In particular, sociability was identical in patients and controls in the adolescent study, the frequency of psychotherapy was not significantly different (29% among patients vs. 18% among controls) and there was no clinical evidence of significant psychiatric problems among patient participants. Finally, the cognitive difficulties reported were not specific to reading. Indeed, only 15% of the adults reported reading difficulties and, among adolescents, report of reading difficulties was not significantly higher in patients than in controls. The present study has limitations. No neuropsychological tests were performed, although previous studies have shown that scores on questionnaires (teachers’ report) on learning difficulties in patients treated for cerebellar tumours correlated significantly with IQ scores [33]. The approach was deliberately ecological in order to examine the long-term functional outcome of patients treated for low-grade cerebellar astrocytoma in childhood. The adolescent sample was small, so that the comparisons between patients and controls lacked statistical power. Some patients who corresponded to the inclusion criteria did not participate, but the medical data did not differ between participants and non-participants. The number of patients did not allow a calculation of the reliability of the questionnaire, which needs further studies. Significant differences between patients and controls, despite the small size of the sample, are in favour of the validity of the questions. In conclusion, permanent neurological deficits were reported by both adolescents and adults treated for lowgrade astrocytoma in childhood. These deficits are neurological symptoms of cerebellar dysfunction. Nonetheless, the long-term functional outcome was favourable for the vast majority of patients. Brain stem involvement, post-operative mutism and complications were clearly associated with more negative long-term functional outcomes. Young age at surgery and post-operative complications were associated with school grade repetition. No difference between patients and controls was observed concerning parents’ answers on their child’s QoL, although parents of patients tended to report more learning difficulties, depression/anxiety and hyperactivity/ disruptive behaviour. These findings show that, although most patients are able to lead a close-to-normal life, careful neurological, cognitive and behavioural evaluations after the end of the treatment and at every important step in their school career should contribute to identifying difficulties and to finding the most appropriate solutions.
Pilocytic astrocytoma outcome
DOI: 10.3109/02699052.2014.975281
Acknowledgements We thank the participants for their contribution to this study.
20.
Declaration of interest
21.
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The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. N. Ait Khelifa-Gallois was supported by grants from ‘Canceropoˆle Ile de France’ and ‘Ligue contre le cancer’.
22.
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Appendix A. Adolescent study 1. The adolescent self-report (a) General questionnaire: Please answer the following questions:
Personal educational history: (1) Are you presently attending school? (Yes/No), (2) What class? (3) Last diploma obtained? (4) School grade repetition? (Yes/No), (5) How many times have you repeated a school grade? (6) Special school? (Yes/No) Rehabilitation (Yes/No): (1) Psychotherapy, (2) Remedial teaching, (3) Speech therapy (4) Occupational therapy, (5) Physiotherapy, (6) Psychomotor therapy, (7) Other rehabilitation. (b) Neurological, cognitive and academic difficulties: Presence of everyday difficulties: (Yes/No) ‘Do you have difficulties in the following areas?’ (Yes/No). Reading difficulties: (1) Learning to read, (2) Reading aloud, (3) Reading silently without saying the words aloud, (4) Reading silently without whispering, (4) Answering questions about a text, (5) Finding information in a text, (6) Moving from one line to another, (7) Enjoying reading, (8) Difficulties reading, (9) Slowness in reading. Difficulties in mathematics: (1) Mathematics in general, (2) Solving additions on paper, (3) Solving subtractions on paper, (4) Multiplications, (5) Divisions, (6) Learning the multiplication tables, (6) Solving problems, (7) Mental calculation, (8) Performing simple calculations without a calculator, (9) Geometry.
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Memory difficulties: (1) Learning a lesson, (2) Remembering what
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has been learned, (3) Visual memory of graphic representations, (4) Learning poems, (5) Memorizing instructions. Attention difficulties: (1) Remaining attentive during a lesson. Slowness: (1) Completing exercises during exams, (2) Taking notes during lessons. Writing difficulties: (1) Writing, (2) Writing fast, (3) Writing legibly. Difficulties talking or expressing yourself: (1) Expressing views orally, (2) Hesitating to use long or complicated words, (3) Speaking as fast as most people, (4) Controlling your voice. Difficulties in manual skills: (1) Manual difficulties, (2) Using a ruler or compass, (3) Performing everyday gestures, (4) Slowness dressing, (5) Slowness housing, (6) Slower gestures than most people, (7) Clumsiness drawing simple things, (8) Reproducing a rhythm by tapping on a surface. Balance difficulties: (1) Balance difficulties in general, (2) Walking on a beam, (3) Walking on the edge of a narrow pavement, (4) Riding a bicycle, (5) Running down stairs Sports practice difficulties: (1) Are you sporty? (2) Do you do a sport now? (3) Do you have difficulties doing sports at school? (4) Do you like sports at school?
2. Parental questionnaire (a) General questionnaire: (1) Questionnaire completed by: the mother, the father, both parents.
(2) Educational level of the parents: (1) father: high school diploma? (2) mother: high school diploma? (‘Baccalaureat’) (Yes/No)
(3) Did you talk about your child’s illness to the school staff? (Yes/No)*
(4) Are you satisfied with: (1) the medical information you received; (2) the educational institution attended by your child; (3) the rehabilitation programmes (Very satisfied/fairly satisfied/Rather dissatisfied/very dissatisfied)*
(b) Questions about present type of school frequented, current learning difficulties:
Does your child have learning difficulties? (Yes/No) What kind of difficulties does he/she have? (Several answers possible): (1) Slowness, (2) Attention, (3) Memory, (4) Language, (4) Difficulties in French (5) Difficulties in mathematics, (6) Behaviour problems at school, (7) Other (please specify). (c) Global Evaluation Scale (Soria et al. [16]).
(d) Behaviour Questionnaire (Sabbagh et al. [17]).
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B. Adult study: Semi-structured telephone interview 1. General questionnaire (Yes/No) Academic and professional achievement: Educational/occupational: Student/Working/Looking for a job/ Sheltered workplace. Personal educational history: (1) school grade repetition? (Yes/No), (2) how many times did you repeat a school grade? (3) what is the highest diploma you obtained? (4) did you pass the Brevet des Colle`ges (middle-school national diploma)? Functional independence: (1) are you financially independent? (2) Where do you live (several answers possible): with your parents/ alone/with a partner/other situation? (Specify), (3) do you have a driving license? Rehabilitation: (1) Psychotherapy, (2) Remedial teaching, (3) Speech therapy, (4) Occupational therapy, (5) Physiotherapy, (6) Psychomotor therapy, (7) Other rehabilitation. Satisfaction with the medical information received: (Very satisfied/ Fairly satisfied/Rather dissatisfied/very dissatisfied)
2. Questionnaire about neurological, cognitive and academic difficulties: ‘Do/did you have difficulties in the following areas’ (Yes/No): Attention: (1) sustaining attention during a lesson? (2) Are you easily distracted? Memory: (1) learning a lesson? (2) remembering a lesson? (3) learning the multiplication tables? (4) learning a poem? (5) memorizing a plan or a figure? (6) remembering an instruction? Balance: (1) do you have any balance difficulties? (2) walking on a beam, (3) walking on the edge of a narrow pavement, (4) riding a bicycle, (5) running down stairs? Mental calculation: do you have difficulty doing additions? subtractions? multiplications? divisions? in problem-solving? Slowness: are you slow completing a task? Do you have difficulty finishing a task in a given time? Manual skills and writing: (1) do you have difficulty using a ruler? (2) using scissors, (3) did you change your dominant hand after surgery? (4) do you have difficulty writing? (5) writing fast? (6) is your handwriting legible? (7) do you get cramp when writing? (8) do you use a computer? Language and reading difficulties: (1) do you have difficulties in written expression?, understanding the structure of a text? (2) can you easily answer questions correctly after reading a text? (3) do you have difficulties reading aloud?
