Motor performance after treatment of pilocytic astrocytoma in the posterior fossa in childhood

Abstract Background Pilocytic astrocytoma is the most common brain tumour type in childhood located in the posterior fossa, and treated mainly with surgery. These tumours have low mortality, but knowledge concerning its long‐term outcome is sparse. Aims The aim was to investigate if patients treated for pilocytic astrocytoma in the posterior fossa had motor complications, including balance, motor and process skills. Methods and Results This descriptive single‐centre study includes eight children and 12 adults, treated for pilocytic astrocytoma as children. Motor performance was investigated with Bruininks–Oseretsky Test of Motor Proficiency, Second Edition, and dynamic balance with the mini‐balance evaluation systems test. Physiological cost index, six‐minute walk test, hand grip strength and assessment of motor and process skills were also evaluated. Ten patients reported motor difficulties, mainly from the upper limbs. The motor performance test showed results within normal limits except for manual dexterity, which was significantly below mean (p = .008). In the dynamic balance test patients had significantly lower results compared with controls (p = .036). Physiological cost index, six‐minute walk tests and hand grip strength showed results within normal limits. In the Assessment of Motor and Process Skills, patients over 16 years had significantly lower results compared with test norms for motor activities of daily living (ADL) and 30% of all patients scored below the cut‐off level for difficulties with motor skills. Conclusions Motor performance for patients treated for pilocytic astrocytoma in the posterior fossa in childhood is satisfactory but some patients display difficulties with balance, manual dexterity and ADL motor skills. Thus, it is important to identify those in need of motor follow‐up and training.

grade tumours, 3 but in an earlier study, we found complications also among children treated for low-grade tumours. 4 Pilocytic astrocytoma is the most common brain tumour type in childhood located in the posterior fossa, and treated mainly with surgery. These tumours have a low mortality and favourable long-term outcome. 5,6 Although there are studies describing neurological, cognitive and behavioural complications among these patients, there is still a lack of knowledge concerning the extent of late effects. [7][8][9][10][11] In a study by our group, we found favourable clinical outcome, but 40% reported learning difficulties. 12 The cerebellum plays important roles in the acquisition of motor skills. This involves development from controlled to automatic processing, where movements that initially require problem solving and attention become increasingly more efficient and require less attention. 13 Diseases involving the cerebellum can lead to ataxia, which is characterised by incoordination of balance, gait, extremity and eye movements and dysarthria. 14 When assessing conditions involving the cerebellum, the concepts of postural control and balance are important.
Postural control is defined as the act of maintaining, achieving or restoring a state of balance during any posture or activity. 15 Balance is defined as the ability to maintain the body's centre of mass over its base of support, and is a composite ability involving integration of information from several sensory systems. 16 Like any other motor skill, postural control strategies can become more efficient with training and practice. 15 Motor consequences have not been as extensively evaluated as cognition in studies of children treated for brain tumours. 17,18 However, in a study by Piscione survivors of posterior fossa tumours demonstrated decreased physical functioning 17 and in another study by Rueckriegel, results showed impairment of fine motor function. 19 Against this background, more knowledge is needed about the type and extent of motor complications in patients treated for pilocytic astrocytoma in the posterior fossa. Our hypothesis was that these patients had affected motor performance. Therefore, our aims were to investigate whether patients had self-perceived difficulties with motor performance. We also wanted to investigate how they performed in tests of motor proficiency, including balance and if they had diminished gait efficiency, affected functional exercise capacity and reduced grip strength.
Lastly, we wanted to investigate whether the patients had affected motor and process activities of daily living (ADL) skills, and if the patients with motor difficulties also reported difficulties in school.

| Participants
This single-centre study was performed 2015-2017 at Uppsala University Children's Hospital, Sweden, a tertiary referral centre for children with tumours in the central nervous system (CNS), serving six counties in mid-Sweden with a population of 1.7 million people.
Patients were retrieved from the local and the National Brain Tumour Registry. A total of 27 patients <18 years of age with a low-grade astrocytoma in the posterior fossa diagnosed and treated in childhood between 1995 and 2011 were identified. At the time of this investigation, nine were children (9-17 years) and 18 adults (21--33 years). Patients were included at least 5 years after end of treatment. This study includes the same patient group as a former study from our research group, 12 except two adults who only participated in telephone interviews. Three patients did not answer several invitations, and two declined participation. Thus, 20 patients agreed to take part (12 adults and eight children; 74%). The mean age at tumour presentation was 8.3 years (standard deviation [SD] 4.3), and the mean age at participation in the study was 20.2 (SD 7.3) years. Mean time from diagnosis to participation was 12.2 (SD 4.6) years.
The included patients showed normal psychomotor development prior to diagnosis, except for one patient, diagnosed at 1 year of age with a delayed psychomotor development. All patients were treated surgically, and in 17 patients, the operation was considered as a complete resection. Three patients had a remaining tumour and were reoperated shortly after the initial operation. Another three patients relapsed; one was treated with re-surgery, one with re-surgery and chemotherapy (initially vincristine and carboplatin, later changed to vinblastine because of hearing loss) and one with gamma knife radio surgery. None had a metastatic tumour.
Nine patients had contact with a physiotherapist immediately after treatment.

| Procedure
Upon acceptance, participants were invited to the Folke Bernadotte Regional Rehabilitation Center in Uppsala to undergo investigations performed by a multi-professional team, 2 days for adults and 3 days for children. A schedule was made for the activities during the days, including a lunch break and rest between the different tests. The investigations included an interview, a neurological examination, tests of motor performance and assessment of motor and process skills. Physiological cost index Measurements of energy expenditure are often used to quantify gait efficiency by using heart rate recordings. 21 These provide an estimated measure of energy expenditure, based on a linear relationship between heart rate and oxygen uptake at a sub-maximal activity level.

| Tests of motor performance
Physiological cost index (PCI) is calculated as a quotient of the difference between work and rest heart rate divided by the walking speed, expressed as heartbeats per metre: PCI ðbeats=metreÞ ¼ work heart raterest heart rate ðbeats=minÞ walking speed ðmetre=minÞ The patients walked 375 m indoors at a self-selected speed. Directly after the test, the exertional effort was assessed according to the Borg rating of perceived exertion (RPE) scale where the lowest level six, corresponds with no exertion and the highest 20, with maximal exertion. 22 The reference values (M 0.44, SD 0.13) were taken from a study by Bratteby Tollerz, 21 which included 20 healthy children aged 5-16 years.
These values have been used for all patients, based on the assumption that energy cost will be approximately the same for all ages, because rest and work heart rate decreases with age and walking speed increases. 21 Six-minute walk test The six-minute walk test (6MWT) is a method to assess the submaximal level of functional exercise capacity. The test measures the distance in metres the patient can walk on a flat, hard surface in a period of 6 min. 23 The level of exertion during the test was assessed by the RPE scale. Reference values, divided into age groups and sex, were taken from a study by Geiger 23 including 528 children.

Hand grip strength
Grip strength is routinely assessed to evaluate upper extremity impairments, strength changes and work capacity. It provides information about hand function 24 and is an indicator of general health. 24 A three Jamar hydraulic hand-held dynamometer (Samons Preston Rolyan, Bolingbrook, IL) was used to measure grip strength in pounds (lb). Normative data, divided into sex and age groups, were collected from a study by McQuiddy, 24 where 1508 students aged 6-19 years participated, and from a study by Fain,25 with 237 participants, aged 20-34 years.

Mini-balance evaluation systems test
The mini-balance evaluation systems test (Mini-BESTest) is a clinical balance scale including 14 items that examine motor performance tasks related to dynamic balance, such as dynamic body stability, transfers, gait, variation of support surfaces and visual conditions, obstacle negotiation, reaction to external forces and performance during dual tasking with cognitive challenge. 26 The administration time is about 15 min, which is an advantage over more extensive instruments, and is used and validated to assess balance impairments in several conditions, including neurological diseases. 26 In this study, we into Swedish and validated for Parkinson's disease and stroke. 27 In the original publication, 28-point summated scores were used, and only the most affected side for items of one-leg stance and lateral compensatory stepping were included. However, when comparing the effects of using a 32-point or a 28-point scoring scale, the effects on the results were minimal. 28

| Reported motor performance
Fourteen participants, five children and nine adults reported that they had motor symptoms postoperatively, mainly difficulties with balance and stiffness in the neck. In the study interviews, 10 participants, four children and six adults, reported that they had motor difficulties that affected their motor performance to some extent (Table 1). Six had difficulties affecting the upper limbs and two affecting balance, while one experienced one-sided muscular weakness. One patient had a pronounced difference in leg length present before the tumour diagnosis.

| BOT-2
All 20 participants performed BOT-2 ( Table 2), The results were within normal limits compared with norms, except for manual dexterity, which was significantly below mean (p = .008), and a tendency towards low results in the subtest balance (p = .051). Nine patients had a result below À1 SD in balance and seven in manual dexterity.

| PCI
The patients had results within normal limits compared with the reference values (M 0.43, SD 0.14), and rated the exertion as very light.

| 6MWT
All results were within normal limits compared with norms. Female participants scored exertion as somewhat hard, while males 12-15 years scored exertion as very light and those above 16 years as light.

| Hand grip strength
All results were within normal limits compared with the age norms.
All participants could perform the test properly and understood the test instructions. There were no significant differences between the patients and controls concerning age, length and weight (p = .857, p = .884 and p = .657, respectively). The patients had significantly lower results compared with the controls for the whole sample (p = .036) and for the children (p = .016) ( Table 3).

| AMPS
All patients performed AMPS (

| DISCUSSION
In the present study, we investigated motor performance and the abil- where children treated for cerebellar tumours were investigated. 17,19 In the study by Piscione, patients treated for pilocytic astrocytoma had results in the low normal range in BOT-2 for body coordination (where the subtest balance is included). 17 Rueckriegel 19  They argue that due to the fact that maturation of the cerebellum is still ongoing during childhood and adolescence, functional recovery may differ depending on age at injury. However, they state that the lesion site and not age-at-surgery is critical for motor recovery.
Impairments in balance and upper-limb function were linked to lesions of the inferior vermis and the deep cerebellar nuclei. 33  practical subjects including physical education. The results showed that children treated for brain tumours had significantly lower grades compared with controls, 34 without any significant impact of tumour grade.
This underscores that also children treated for low-grade tumours are at risk for lower results in physical education. Exercise training has proven to improve physical functioning, mood and cognitive performance, 35 which also has been shown in children treated with radiation. 35

| CONCLUSIONS
The long-term functional outcome for children treated for pilocytic astrocytoma in the posterior fossa is favourable. However, some patients have difficulties with motor performance, especially balance, manual dexterity and motor ADL. This may lead to challenges in daily life, especially among those who also have learning difficulties. Therefore, it is imperative to identify those in need of more thorough motor and cognitive follow-up programs, including interventions in school.
Moreover, there is a need to evaluate the effect of motor training among these patients and to establish appropriate collaboration between paediatric neuro-oncology clinics and the educational system.

ACKNOWLEDGEMENTS
This study was supported by grants from the Swedish Childhood Cancer Foundation, the Hedström Foundation and the Gillbergska Foundation. Financial support was also provided through a regional agreement on medical training and clinical research (ALF) between the Uppsala County Council and Uppsala University Children's Hospital.
Special thanks to Margareta Dahl MD, PhD, associate professor of paediatric neurology, for supervision and planning of the study. We would also like to thank Mona-Lisa Wernroth and Ulrika Andersson for help with the statistics. The English language of this manuscript was revised by senior lecturer Donald MacQueen.

CONFLICT OF INTEREST
The authors have stated explicitly that there are no conflicts of interest in connection with this article.

AUTHOR CONTRIBUTIONS
All authors had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data.

ETHICAL STATEMENT
The study was approved by the Regional Ethical Board (EPN Uppsala Log. No. 2015/107). Informed consent was obtained from all participants included in the study.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.