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Abstract

Background: Short and long-term consequences after treatment for childhood fossa posterior tumour are extensively reported in literature; however, papers enlightening physical function throughout rehabilitation and its correlation with Intelligence Quotient are sparse. Physical dysfunctioning may impact the child’s development, activities daily living, the ability to return to school and socialize with friends.

Methods: A retrospective cohort study design was used with data of 56 children who followed a multidisciplinary program in the Child Rehabilitation Centre, Ghent University Hospital, in the period 2005-2020. Descriptive statistical analysis was performed with the use of non-parametric tests and linear regression for the relationship of gross motor functioning and IQ.

Results: This report shows impaired motor and intelligence performance in children with a fossa posterior tumour. Furthermore, our study indicated that multidisciplinary rehabilitation is beneficial, but is not able to counteract further decline of several motor skills and intelligence during oncological treatment, more specifically in children with a medulloblastoma. A correlation between gross motor function and total IQ was found. 

Conclusion: Paediatric survivors of a fossa posterior tumour experience impaired physical and intellectual functions, with more decline during oncological treatment despite simultaneously multidisciplinary rehabilitation.

Key words

 Fossa posterior tumour, child, rehabilitation, motor functioning, intelligence quotient

Introduction

In the paediatric population, one fourth of the cancer diagnoses are brain tumours with an overall incidence between 2.65 and 5.7 per 100000 children and adolescents [1,2]. More than half of these tumours are located within the fossa posterior, involving the cerebellar hemispheres, brainstem, fourth ventricle or cerebellopontine angle [3]. Various histopathological types of fossa posterior tumours are described, according to the World Health Organization (WHO) 2007 classification criteria. The three most common fossa posterior tumours are medulloblastoma (40%), pilocytic astrocytoma (20–35%), and ependymoma (10%) [4]. Treatment of children with fossa posterior tumours, has improved significantly during the last years with an overall current 5-year survival rate above 70% [5,6].

Depending on the WHO classification of the tumour and protocol guidelines, a total microsurgical removal of the tumour is in most cases the first objective, followed by complementary treatments such as chemotherapy and radiotherapy. Although the role of the fossa posterior tumour on preoperative functioning may be difficult to determine because most of the time an emergency surgery is needed for an intracranial hypertension, we have to take into account that also oncological treatment may lead to severe short and long term physical and intellectual complications [7,8]. First, there is a crucial balance between the extension of neurosurgical removal and postsurgical neurological deficits such as cerebellar mutism, speech deficits, cranial neuropathies, cognitive deficits and cerebellar ataxia [9]. Secondly, although adjuvant chemotherapy improved survival rates dramatically, there is a known adverse effect on brain development, the so called “chemobrain” [10,11]. And last but not least, also radiotherapy may have a detrimental effect on neuropsychological development, particularly in small children [12].

Many previous papers report extensively short- and long-term consequences after treatment for childhood fossa posterior tumours, however literature specifically enlightening the physical functioning is rather sparse [13,14]. Nevertheless, physical functioning is important as it may impact the child’s further development, activities of daily living, the ability to return to school and to socialize with his/her friends.

In the acute postoperative phase, there is often a profound axial hypotonia and ataxia [15], whereas this ataxia may persist for more than a year post surgery [8]. Furthermore, paediatric survivors of a fossa posterior tumour show decreased subscale scores on the Bruininks-Osteretsky Test of Motor Performance, Second Edition (BOT-2), compared to normative data. Moreover, this impaired physical functioning is most remarkably in the subscale ‘balance’ [16]. Dreneva et al. concluded that fossa posterior tumour survivors demonstrate a permanent impairment of the postural function, and the authors attribute these deficits to both the tumour itself and its further oncological treatment [17].

Given the fact that therapeutic interventions targeting motor skills and cognitive functions can be effective in this population, children with a history of a fossa posterior tumour usually start with multidisciplinary rehabilitation in specialized centres as soon as possible [18]. However, little is known about the progression these children make on physical performance during this rehabilitation period. Forsyth et al. reported a strong relation between the amount of active practice and gross motor recovery trajectories in children with an acquired brain injury [19]. Yet, understanding what difference rehabilitation can make in the physical outcome of these survivors of a fossa posterior tumour is a big challenge, because of the strongly individualized rehabilitation programs and the influence of protracted oncological treatment.

The main goals of our study are 1) to examine physical functioning and the intelligence quotient (IQ) of paediatric survivors of a fossa posterior tumour, using a standardized measure with comparison to normative data, 2) to evaluate progression during a multidisciplinary rehabilitation program and 3) to determine if there is a difference in physical functioning and the intelligence quotient (IQ) between the different histopathological tumours (medulloblastoma, ependymoma, astrocytoma). Because cognitive function is related to gross motor function in small children and children with cerebral palsy, our fourth goal is to search for a correlation between the gross motor functioning and cognitive functioning in children with a fossa posterior tumour [20,21].

Materials and Methods

Participants: A retrospective cohort study design was used, with data collected from the electronic patient record platform of the Children’s Rehabilitation Centre, Ghent University Hospital, Belgium. Children between the age of 0-15 years, diagnosed with a medulloblastoma, ependymoma or pilocytic astrocytoma in the fossa posterior, were selected in the period 2005-2020. They were included in the study if they underwent a (partial) neurosurgical resection of the tumour and followed a multidisciplinary rehabilitation program. Exclusion criteria were other histopathological types of fossa posterior tumour and children who didn’t had a neurosurgical intervention. This study was approved by Ghent University Hospital Research Ethics Committee (Figure 1).

Figure 1. Flowchart of data collection with exclusion criteria.

Physical functioning: To determine physical functioning at the onset and the end of the rehabilitation period, registered data were collected describing the force and range of motion. Furthermore, results of 3 norm referenced tools to measure gross and fine motor skills in children were assembled: the Bruininks-Oseretsky Test of Motor Proficiency Second Edition (BOT-2), the Peabody Developmental Motor Scale (PDMS-2) and the Purdue Pegboard Test (PPT).

The Bruininks-Oseretsky Test of Motor Proficiency Second Edition (BOT-2) delivers a comprehensive measure of gross and fine motor skills in children age 4 to 21. The BOT-2 has 53 items organised into four composites: fine motor manual control composite, manual coordination composite, body coordination composite and strength and agility composite. These composites are further divided into eight subscales [22,23].

The Peabody Developmental Motor Scale (PDMS-2) assesses gross and fine motor skills of young children from birth through 5 years. This test is composed of six subsets, which include: reflexes, stationary, locomotion, object manipulation, grasping and visual motor-integration. The PDMS-2 categorises performance into 1 of 7 categories, with higher scores reflective of better performance [24,25].

The Purdue Pegboard Test (PPT) is an assessment of fingertip dexterity and gross movement of the arm, hand and fingers. The child is seated at a table with the testing board in front of him/her. The testing board consists of two vertical rows of 25 small holes down the centre and 4 cups across the top with pins, washers, and collars. The clinician administers the following subtests: place as many pins as possible down on the row within 30 seconds with the right hand, with the left hand and with both hands. The last subtest is the use of both hands simultaneously while assembling pins, washers, and collars as many as possible within 60 seconds.

Cognitive functioning: The Wechsler Intelligence Scale for Children (WISC) is a widely used standardized tool to assess intelligence in children between the age from 6 to 17 years [26].  Different editions of the test were used in the study time frame 2005-2020, namely the third and fifth edition.

The Wechsler Preschool and Primary Scale of Intelligence (WPPSI)-III- NL is an intelligence test for children from the age of 2 year 6 months to 7 years 11 months [27].

The assessment of intelligence in children with problems in the area of verbal communication (e.g., cerebellar mutism, verbal apraxia, foreign language) was performed with the Snijders-Oomen Nonverbal Intelligence test Revised (SON-R). For the administration of this test, neither the examiner nor the child is required to speak or write. The SON-R 2½-7 is suitable for children between the age of 2,5 and 7 years, the SON-R 6-40 is used in older children [28].

Statistical analysis: Descriptive statistical analysis was performed with SPSS version 27.0 (IBM, Armonk, NY, US) and Excel (Microsoft Office) for the graphic illustrations. Comparison of continuous variables between groups were performed using the non-parametric Wilcoxon (2 groups) or Kruskall-Wallis (more than two groups). Comparison of categorical variables was performed with non-parametric chi square test.

Corrected p-values lower than 0.05 were considered significant.

The relationship of physical functioning and cognitive status was assessed by a linear regression (Pearson correlation).

Results

Participants: Fifty-six children were included in our study in the time period of 2005-2020. Thirty-five (62.5%) males and 21 (37.5%) females, with an average age of 6.51 years (SD 4.13). The average period of the multidisciplinary rehabilitation was 444 days, equalling 1 year and 2 months. Multidisciplinary rehabilitation was started immediately after the neurosurgical procedure and consisted of physiotherapy, occupational, speech-language and neurocognitive training, with a frequency of 3 to 5 times a week (2,5 hours/day). The most common tumour histology was a medulloblastoma (50%), followed by a pilocytic astrocytoma (37.5%) and an ependymoma (12.5%).

At presentation in the hospital nearly 70% of patients needed an emergency surgery with establishment of an External Ventricular Drain (EVD) for intracranial hypertension.

Forty-one-point one percent of the included children had a relapse tumour with a significant predilection for an ependymoma (p=0.028), 19.6% died, most of them diagnosed with a medullobastoma (10/11 children) and only one child (1/11) deceased from an ependymoma.

The characteristics of the population are available in (Table 1).

Table 1. Patient’s demographics.

		Number	%
Tumour Histology	Ependymoma	7	12,5
	Medulloblastoma	28	50
	Pilocytic Astrocytoma	21	37,5
Sex	Male	35	62,5
	Female	21	37,5
Mean Age (SD)		6,512	4,129
External Ventricular Drain at presentation	Yes	38	67,9
	No	18	32,1
Relapse Tumour	Yes	23	41,1
	No	33	58,9
Deceased	Yes	11	19,6
	No	45	80.4

Physical functioning: To determine physical functioning in our study population with fossa posterior tumour at the onset and at the end of the rehabilitation period, registered data were collected describing the “balance” and “range of motion”. Furthermore, results of the BOT-2, PDMS-2 and PPT were assembled and analysed.

Balance and range of motion: Based on the professional experience of the physiotherapist, performance in balance and range of motion was defined as “normal” and “abnormal”.

Disbalance was mainly associated with medulloblastoma at onset of rehabilitation (p<0.001) as well at the end of the rehabilitation period (p<0.076). The range of motion in the upper limbs was seldom disturbed, however a reduction of the range of motion in the lower limbs was often seen in children with a medullobastoma. Moreover, this reduction in mobility in the lower limbs was unexpectedly more explicit at the end of the rehabilitation period compared to the beginning of the rehabilitation. The statistical significance (p) was calculated between this assessment and the different tumour histologies (Table 2).

Table 2. “Balance and Mobility” in our cohort children with a fossa posterior tumor.
*No statistical significance could be calculated since there are only normal values withheld.

Physical functioning parameters	Tumour histology							Statistical significance (p)
	Medulloblastoma			Ependymoma		Pilocytic Astrocytoma
	Normal	Abnormal		Normal	Abnormal	Normal	Abnormal
Balance before rehab (n=16)	0%		68.8% (11/16)	6.3% (1/16)	0%	0%	25% (4/16)	<0.001
Balance after rehab (n=8)	0%		50% (4/8)	12.5% (1/8)	0%	25% (2/8)	12.5% (1/8)	<0.076
Mobility upper limbs before rehab (n=47)	44.7% (21/47)		2.1% (1/47)	10.6% (5/47)	0%	38.3% (18/47)	4.3% (2/47)	<0.637
Mobility upper limbs after rehab (n=27)	55.6% (15/27)		0%	7.4% (2/27)	0%	37% (10/27)	0%	*
Mobility lower limbs before rehab (n=48)	35.4% (17/48)		10.4% (5/48)	10.4% (5/48)	0%	41.7% (20/48)	2.1% (1/48)	<0.138
Mobility lower limbs after rehab (n=28)	35.7% (10/28)		21.4% (6/28)	7.1% (2/28)	0%	35.7% 10/28)	0%	<0.057

Gross motor functioning: Gross Motor functioning is assessed using the Bruininks-Oseretsky Test of Motor Proficiency Second Edition (BOT-2) and the Peabody Developmental Scale (PDMS-2).

The Bruininks-Oseretsky Test of Motor Proficiency Second Edition (BOT-2): Motor-area composite score distributions of “Body Coordination” and “Strength and Agility” were illustrated using boxplots and scatterplots (Figure 2). The norm referenced average for each composite is a score 50.

The composite scale “Body Coordination” shows a positive tendency throughout the rehabilitation. More specifically, the children perform wat a mean of 33 (SD 4.947/n=18) at the beginning of their rehabilitation and improve to a mean of 37.8 (SD 8.189/n=10) at the end, which is however still under the average norm referenced value. 

The composite score of “Strength and Agility” seems not to improve during the rehabilitation with a starting mean of 40.53 (SD 9.716/ n=16) and a final mean of 39.91 (SD=11.149/ n=11).

Because of the heterogeneous data, in which the starting and ending values weren’t always of the same patients a calculation of the statistical significance of the rehabilitation was not possible (Figure 2).

Figure 2. Boxplot of the gross motor-area composite score distributions “Body Coordination” and “Strength and Agility” of the BOT-2. The horizontal line illustrates the norm referenced standard score.

The Peabody Developmental Motor Scale (PDMS-2): Subscales “Locomotion”, “Object Manipulation” and “Stationary” were used to determine gross motor function in our study cohort of children with a fossa posterior tumour. The norm referenced average of every subscale is a score between 8 and 12.

The mean of the subscale “Locomotion” in our study population is 4.67 (SD=2.5/n=9) at the beginning of the rehabilitation and 6.20 (SD=2.864/n=5) at discharge. Regarding the subscale “Object Manipulation”, a positive tendency throughout the rehabilitation is found with a starting mean score of 8 (SD=2.366/n=6) and at the end 13 (SD=4.243/n=2). Finally, the subscale “Stationary” shows no progress with similar scores at the start and the end of the rehabilitation, respectively 7.14 (SD=2.410/n=7) and 6.50 (SD=3.536/n=2) (Figure 3).

Figure 3. Scatterplot of the gross motor subscale “Locomotion”, “Object Manipulation” and “Stationary” of the PDMS-2. This figure illustrates the values of the scale score at respectively the start and end of the rehabilitation. The median score is illustrated by the triangle symbol. Average scoring of these subsets is between 8 and 12, maximum scale score is 20.

Fine Motor Functioning: Fine Motor functioning was assessed by the BOT-2, the PDMS-2 and the Purdue Pegboard. 

The Bruininks-Oseretsky Test of Motor Proficiency Second Edition (BOT-2): Fine motor-area composite score distributions of “Fine Manual Control” and “Manual Coordination” were illustrated using a scatterplot (Figure 4). The norm referenced average for each composite is a score 50.

Figure 4. Scatterplot of the Fine motor subsets “Fine Manual Control” and “Manual Coordination” of the BOT-2. It illustrates the values of the scale score at respectively the start and end of the rehabilitation. The median score is illustrated by the triangle symbol. The norm reference average standard score is 50, illustrated by the vertical line.

The mean standard score of “Fine Manual Control” at the beginning was 41.286 (SD 7.544 /n=7), which is under the average value of 50. Throughout the rehabilitation there was an amelioration of the fine manual control, with an increase of the mean to 51.25 (SD 6.551 /n=4)).

Also, the mean standard score of the subscale “Manual Coordination” is located under the average value at the beginning of the rehabilitation, with a score of 37,857 (SD=9.720 /n=7).

Since there was no available data of post rehabilitation Manual Coordination, a comparison could not be made (Figure 4).

Figure 5. Scatterplot of the fine motor subsets “Grasping” and “Visual-Motor Integration” of the PDMS-2. It illustrates the values of the scale score at respectively the start and end of the rehabilitation. The median score is illustrated by the triangle symbol. Average scoring in the norm referenced population of these subsets is between 8 and 12, the maximum scale score is 20.

Figure 6. Bar Charts of the distribution of the percentile ranks of the PPT. The charts representing different subcategories are illustrated in the rows (Left, Right, Assembly and Both). The left column represents the values before the rehabilitation and the right column illustrates the values after the rehabilitation.

The Peabody Developmental Motor Scale (PDMS-2): In the PDMS-2, we focused on the fine motor subtests “Grasping” and “Visual-Motor Integration”. The norm referenced average of every subscale is a score between 8 and 12.

The mean score of the subscale “Grasping” in our study is 9 (SD=3 /n=7) at the beginning of the rehabilitation with a mean of 8 (SD=4.082 /n=11) at the end.  Although both mean scores lie within the average range, we notice a small decrease between before and after the rehabilitation.

The mean of the subscale “Visual-Motor Integration” is 8.91 (SD=2.3 /n=11) at the beginning of the rehabilitation with a substantial decrease after the rehabilitation to 6.20 (SD=3.347 /n=5), below the average range (Figure 5).

Purdue Pegboard Test (PTT): Scores of the Purdue Pegboard were divided into the percentile ranks to give an insight into the starting values of our group of patients and to compare with the scores at the end of rehabilitation (Figure 6).

In global the percentile values of left and right hand separately, of both hands and the assembly score are most commonly in the lowest percentile (0-10) represented.

After the end of the rehabilitation, there is no improvement of the percentile values with scores over the 50-percentile mark varying from only 10% of the children (scoring of the left hand) to the maximum of 18.2% (scoring of the right hand).

Mean values scores of the percentile ranks score before the rehabilitation below the average marker of 50. Mean score of the Left Hand is 31.667 (SD 21.602/ n=15), of the Right Hand the mean score is 27.857 (SD=27.012/ n=14). Scoring of assembly and of Both Hands have a respectively mean value of 35.0 (SD 29.439/ n=13) and 21.923 (SD 22.130 /n=13). The mean values of the ranks decrease at discharge of the rehabilitation, with a mean value of 18.0 at the Right Hand (SD=25.832/ n=11) and 19.546 (SD=17.670/ n=10) at the Left Hand. The score of the Assembly has a mean value of 26.429 (SD=22.678 /n= 7) and finally, the mean score of the subset of Both Hands is 20 (SD=23.452/ n= 6).

Cognitive functioning: Results of the WPSI-III and WISC III/V edition are displayed in three categories, total IQ score, verbal IQ score and performal IQ score (Table 3). Regardless of the histopathological type, children with a fossa posterior tumour in our study cohort, have a mean total IQ of 90.94 (SD 12.84), with a verbal IQ of 95.11 (SD 14.998) and performal IQ of 87.41 (SD 13.162) at start of rehabilitation. Furthermore, no significant correlation could be found between the total, verbal or performal IQ at the start of the rehabilitation and the underlying tumour histology (p= 0.364, p=0.145 and p= 0.279).

Table 3. The three categories of the Intelligence Quotient (IQ) testing (Total, Verbal and Performal) are categorized by the underlying tumour histology. The mean value of the first test before the rehabilitation and the final test at the end of the rehabilitation is shown.

When analysing the IQ scores at the end of the rehabilitation we see a negative tendency of all values (total, verbal and performal) in children with a medulloblastoma, compared to the initial intelligence performance.

The total IQ score reduces from 92.31 (SD 12.826) to 82.44 (SD 11.980). The verbal IQ score deteriorates from 96.07 (SD 12.899) to 88.33 (SD 12.510) and the performal IQ score decrements from 87.23 (SD 12.969) to 80.56 (SD 80.56). This negative tendency in intelligence performance was however not seen in the small group of children with a pilocytic astrocytoma. Unfortunately, there were no IQ data available at the end of the rehabilitation of the children with an ependymoma. 

Relationship between Intelligence Quotient (IQ) and Motor Functioning:

The relationship between IQ and the gross and fine motor functioning before start of the rehabilitation was investigated by using the Pearson Correlation.

There is strong correlation between the Total IQ and the Body Coordination score (BOT-2) with a positive correlation coefficient of 0.519 (p=0.102/ n=11). A similar strong correlation was found between the Verbal IQ and the Body Coordination subset with a positive value of 0.528 (p=0.144/ n=9). One relationship is strongly negatively correlated, namely the verbal IQ and the Object Manipulation subset with a Pearson score of -1.000 (p<0.001/ n=2), however we have to be cautious with this conclusion because of the very small number of children.  The other investigated correlations do not show a strong correlation (in a positive or negative way). The correlation between the IQ and fine motor functioning shows varying results, with a strong negative correlation between the Visual-Motor Integration (PDMS-2) and the performal IQ. However, as a result of the very low number of data no conclusions can be made (Tables 4 and 5).

Table 4. The Pearson correlation is depicted between the total, verbal and performal intelligence quotient and the different gross motor subscales of the BOT-2 and the PDMS-2. The significance is calculated, with the number of available data of each combination shown.

		BOT-2 Body coordination	BOT-2 Strength and agility	PDMS-2 Locomotion	PDMS-2 Object Manipulation	PDMS-2 Stationary
Total IQ	Pearson Correlation	,519	,317	,197	-,346	-,002
	Sig. (2-tailed)	,102	,372	,751	,775	,998
	N	11	10	5	3	5
Verbal IQ	Pearson Correlation	,528	,426	,078	-1,000	-,235
	Sig. (2-tailed)	,144	,293	,922	.	,765
	N	9	8	4	2	4
Performal IQ	Pearson Correlation	,423	-,099	,616	-,218	,553
	Sig. (2-tailed)	,257	,815	,268	,860	,447
	N	9	8	5	3	4

Table 5. The Pearson correlation is depicted between the total, verbal and performal intelligence quotient and the different fine motor subscales of the BOT-2 and the PDMS-2. The significance is calculated, with the number of available data of each combination shown.

		BOT-2 Fine Manual Control	BOT-2 Manual Coordination	PDMS-2 Grasping	PDMS-2 Visual-Motor
Total IQ	Pearson Correlation	-,158	-,099	-1,000	,064
	Sig. (2-tailed)	,899	,937	.	,959
	N	3	3	2	3
Verbal IQ	Pearson Correlation	-,785	-,094	-1,000	1,000
	Sig. (2-tailed)	,426	,940	.	.
	N	3	3	2	2
Performal IQ	Pearson Correlation	,436	,500	.	-,904
	Sig. (2-tailed)	,713	,667	.	,281
	N	3	3	2	3

Discussion

This retrospective study evaluates motor and neurocognitive functioning in children with a history of a fossa posterior tumour. Furthermore, we tried to enlighten the potential positive effects of an intensive rehabilitation program in association with oncological treatment.

In correlation with previous literature, nearly all children suffered from a disturbed balance at the time of administration in the Child Rehabilitation Centre, which was mainly associated with a medulloblastoma [16,17,29]. This postural problem was most likely caused by the tumour invasion or derived from an extensive neurosurgical removal. Despite intensive physiotherapy, the same poor results were seen at the end of the rehabilitation period (mean period 1 year and 2 months). This finding indicates either a more permanent cerebellar dysfunction or the adverse effect of chemotherapy and craniospinal radiotherapy on balance during rehabilitation.

Besides the disturbed balance, other gross motor function difficulties were recognized in these children. A decrease in active and passive range of motion of the upper and lower limbs was observed at the time of administration in the rehabilitation centre (before start of chemotherapy and radiotherapy). This finding is not yet described in literature, and could be related to post-neurosurgery immobility, pain or fatigue. Notwithstanding the positive evolution of mobility in the upper limbs, we noted a further deterioration of mobility in the lower limbs (especially ankle dorsiflexion) in children with a medulloblastoma at the end of the rehabilitation period, which was rather unexpected. The adverse effects of chemotherapy agents, such as Vincristine, on balance and gastrocsoleus flexibility are well known, but seem to be poorly counteracted by intensive rehabilitation [30,31].

Despite the disappointing results on balance and range of motion, a positive evolution throughout the rehabilitation was seen on the composite score distributions “Body coordination” and “Strength and agility” of the BOT-2, and the subsets “Locomotion” and “Stationary” of the PDMS-2. At the end of their rehabilitation, our cohort children with a fossa posterior tumour still performed underneath the average on these assessments, however with a better score compared to their initial performance. Only the results on the PDMS-2 subset “Object manipulation” raised to the average level. Impaired gross motor function in child survivors of a fossa posterior tumour is well described in many papers [16,32]. With our findings, we may assume that these children however remain sensitive to physical activity interventions adapted to their medical status. Moreover, gross motor exercise is safe and does not negatively impact the ability to complete chemotherapy and radiotherapy [33,34].

In correlation with the impaired gross motor function, children with a history of a fossa posterior tumour also performed below average on several assessments of fine motor functioning, more specifically on the subsets “Fine Manual Control” and “Manual Coordination” of the BOT-2. The mean score for “Fine Manual Control” of the BOT-2 however improved at the end of the rehabilitation to an average value. Interesting, the mean score distribution of “Grasping” and “Visual-Motor Integration” of the PDMS-2 was situated in the norm reference average range at the beginning of the rehabilitation but dropped underneath the average at the end. Furthermore, also the overall scores of the Purdue Pegboard Test showed a negative evolution throughout rehabilitation. Many papers already described the adverse effect of chemotherapy on fine motor skills in children with acute lymphoblastic leukaemia, with a significant negative correlation between age and motor- or visuomotor performance [35-38]. A study in which the Purdue Pegboard test was conducted in children with ALL, showed a significant slowing of fine motor speed and dexterity for the dominant hand, nondominant hand and both hands [39]. Our findings in children with a fossa posterior tumour are consistent with these papers, which emphasizes the detrimental impact of chemotherapy on fine motor skills due to neuropathy.

The mean intelligence quotient (IQ) of the children in our study cohort was 90.94, with a mean verbal IQ (VIQ) of 95.11 and a mean performal IQ (PIQ) of 87.41 at the time of administration in the child rehabilitation centre, which is low average in comparison with an age-appropriate standard population. Notwithstanding the fact that we can’t speak of an excessive cognitive impairment in these children at start of their rehabilitation program, we may presume a negative effect of initial increased intracranial pressure, the involvement of the cerebellum and the extent of neurosurgery [9,13,40]. A growing number of neuroanatomical and functional neuroimaging studies support the role of the cerebellum in a variety of cognitive processes, such as attention, memory, executive functioning, visuo-spatial regulation, learning, language and behavioural-affective modulation [41]. More specific, “executive functions” (including working memory) have been related to the lateral cerebellar hemispheres, and “attention” to the neocerebellar areas of the hemispheres and the vermis [29]. Despite the fact that in children with cerebellar lesions these cognitive effects are still controversial, we could argue that a lower PIQ compared to the VIQ might be a consequence of executive dysfunction. Another possible explanation may be that a decreased fine motor control in performance tasks may lead to lower scores, resulting in a lower PIQ as reported by Grill et al. [40]. However, when we correlated body coordination with IQ, we obtained the highest correlation coefficients between gross motor control and TIQ and between motor control and VIQ, not with PIQ. Analysing the correlation between fine motor control and PIQ was in our study cohort not conclusive, due to the small number of data. Previous studies in children with a fossa posterior tumour, tend to show less severe cognitive deficits in astrocytoma survivors compared to medulloblastoma survivors [42]. However, at the time of administration in the child rehabilitation centre (post-neurosurgery, no yet adjuvant therapy started), there was no significant difference in cognitive performance between the children with various tumour types. This interesting finding emphasizes the prominent role of adjuvant oncological therapy in the long-term neurocognitive outcome of these children. After an intensive period of multidisciplinary rehabilitation (mean 1 year 2 months), in combination with chemotherapy and radiotherapy, we observed a drop of nearly 10% in all IQ variables (TIQ, VIQ, PIQ) in the cohort children with a medulloblastoma. This decline in overall intellectual ability across time corresponds with multiple follow up studies in these children [13,40,43,44]. This decline in IQ seems to be related to failure to acquire information as expected, and not to a deterioration in existing skills [44-45].

Taking into account our results above, one may conclude that an intensive multidisciplinary rehabilitation program in the post-acute phase during oncological treatment, may have just a limited confident effect on the neurocognitive and physical outcome in children with a medulloblastoma. However, a comparison with children with a fossa posterior tumour who did not receive rehabilitation, is due to ethical reasons obviously not possible in our hospital. Chemotherapy and radiotherapy have a known suppressive effect on brain plasticity, cognitive development, and physical performance [10,11,39,45]. Therefore, the primary goal of early rehabilitation is to try to (partially) counteract serious decline in physical and cognitive skills, and to prevent secondary complications [46]. Some papers have already supported the positive effects of specialized multidisciplinary rehabilitation with personalized intervention goals in these children [46-48]. Our results of moderate improvement in body coordination, locomotion, strength, agility, and fine manual control from below average to low average scores, while receiving chemotherapy, confirm the need of rehabilitation. Furthermore, deteriorating results in balance, range of motion, grasping, visual-motor integration and intellectual capacity throughout rehabilitation, are not an indication that multidisciplinary rehabilitation was not successful. On the contrary, with caution we could assume that these results would be worse without rehabilitation. It is important to accentuate that rehabilitation is more than exercise. Children also learn to use alternative strategies to compensate their cognitive and motor function deficits, which facilitates functional independence and may increase participation in age-appropriate activities [49,50].

Limitations of this study need to be acknowledged. First, this study is a retrospective observational cohort study, in which results were compared with normative data from the different assessments used. Since the inclusion time frame is a period of fifteen years, some measures transformed in different editions (for instance the WISC-III and WISC-V), which could interfere with our results. Second, there is a considerable amount of missing data, which made it difficult to obtain significant conclusions when we compared results at the beginning and at the end of the rehabilitation period. Therefore, our findings need to be interpreted with caution. A prospective longitudinal study in children with a fossa posterior tumour following rehabilitation would be more ideal to gain complete data sets.

Conclusion

This report shows the impaired motor and intelligence performance in children with a fossa posterior tumour and confirms the long-term detrimental effect of oncological treatment. Furthermore, our study indicated that multidisciplinary rehabilitation is beneficial, but is not able to counteract further decline of several motor skills and intelligence in the post-acute phase of treatment, more specifically in children with a medulloblastoma. Although the efficacy of rehabilitation is moderate, we argue that rehabilitation in the post-acute phase of oncological treatment may increase participation in age-appropriate activity requirements. Longitudinal follow-up studies are warranted to assess physical and neuropsychological outcomes in this population.

Acknowledgements

*Robin De Wilde and Mathieu Decock contributed equally to this paper as first co-authors.

Declaration of interest

We have no conflicts of interest to disclose.

References

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