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Outcome measures for children with movement disorders
Accepted Manuscript OUTCOME measures for children with movement disorders Emanuela Pagliano, Giovanni Baranello, Riccardo Masson, Maria Foscan, Maria Teresa Arnoldi, Alessia Marchi, Giorgia Aprile, Chiara Pantaleoni PII:
S1090-3798(17)31694-X
DOI:
10.1016/j.ejpn.2018.01.014
Reference:
YEJPN 2369
To appear in:
European Journal of Paediatric Neurology
Received Date: 31 May 2017 Revised Date:
11 January 2018
Accepted Date: 16 January 2018
Please cite this article as: Pagliano E, Baranello G, Masson R, Foscan M, Arnoldi MT, Marchi A, Aprile G, Pantaleoni C, OUTCOME measures for children with movement disorders, European Journal of Paediatric Neurology (2018), doi: 10.1016/j.ejpn.2018.01.014. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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OUTCOME MEASURES FOR CHILDREN WITH MOVEMENT DISORDERS Emanuela Pagliano, Giovanni Baranello, Riccardo Masson, Maria Foscan, Maria Teresa Arnoldi, Alessia Marchi, Giorgia Aprile, Chiara Pantaleoni
Corresponding Author: Emanuela Pagliano
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Developmental Neurology Unit, C. Besta Neurological Institute Foundation, Milan, Italy Via Celoria 11, 20133 - Milan, Italy
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Tel.: + 39 02 2394.2219 Fax: + 39 02 23942176
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e-mail: [email protected]
ACCEPTED MANUSCRIPT OUTCOME MEASURES FOR CHILDREN WITH MOVEMENT DISORDERS Emanuela Pagliano, Giovanni Baranello, Riccardo Masson, Maria Foscan, Maria Teresa Arnoldi, Alessia Marchi, Giorgia Aprile, Chiara Pantaleoni.
1. Introduction
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ABSTRACT The huge contribution of advances in the pediatric neurosciences, improvements in clinical practice, and new therapeutic options, has led to the development of new models of treatment and rehabilitation for dystonia in the last decade. It is now generally agreed that a multidimensional therapeutic approach is needed for children with motor disorders, whose motor function - conceived as a complex perceptive, motor and cognitive process - is impaired at a crucial time in their development, with a fallout on how their various adaptive functions evolve. Neurophysiological studies, modern neuroimaging techniques, and advances in cognitive psychology have all contributed to improving our understanding of the potential effects of treatments in early age - not only on the symptoms, but also on plasticity processes and neuronal reorganization. The International Classification of Functioning, Disability and Health (ICF) promoted by the WHO, and the diffusion of family-centered models of healthcare have underscored the importance of the ecological perspective with a view to providing effective therapies and a satisfactory quality of life for dystonic children and their families. The advances made in this area have made it necessary to study and developmore appropriate treatment outcome measures. In the light of these aspects, there is still not enough literature on the generally-accepted, exhaustive dystonia assessment tools. Given these limits, it might be useful to discuss the strengths and weaknesses of the main tools currently used in this setting.
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It is extremely difficult to define outcome measures for children with movement disorders. A recent work by Bertucco (2015)1confirmed that the clinical picture of dystonia is more complex in children than in adults, for a number of reasons: • first of all, there is a different etiopathogenesis and a different natural history of the disorders associated with dystonia, from childhood cerebral palsy (which is still the most common) to the genetic, metabolic and degenerative forms; • the early onset of the disorder can interfere with the acquisition of typical motor skills during critical periods of learning and skill development; • the great variety of signs and symptoms involved: different motor disorders often coexist (dystonic postures and movements, chorea and athetosis, and so on), and may be further complicated – especially in the secondary forms - by an associated spastic component (in the socalled “mixed form”); • the changeability over time in the way symptoms evolve, even in the natural history of the same form; • the intrinsic correlation of the motor disorder with perceptive, sensory, cognitive, emotional and communicational-relational problems, which are absolutely interdependent; • and finally - an important aspect especially in terms of rehabilitation - the pathological signs in dyskinetic children are often the result not only of damage to one or more systems controlling 1
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motor behavior, but also of strategies and compensatory mechanisms adopted over time to obtain a functional advantage.
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In addition to this clinical complexity, there is also the problem of how to choose the most appropriate therapeutic strategies. The most important treatments currently available are rehabilitation, pharmacological therapies, botulinum toxin injections (in focal forms), and surgical options such as intrathecal baclofen (ITB), and deep brain stimulation (DBS), and their efficacy needs to be measured and compared 1,2. Finally, a crucial aspect of any treatment and any measurement -particularly evident in this broad group of disorders – concerns patient outcome. What types of outcome can we measure? What is the ideal outcome for a given child with a given disorder, and at what stage of their development? The progress made by the neurosciences, and the consequent development of new rehabilitation methods have confirmed the need for a multidimensional approach to treatment dystonic children, conceiving their motor function as a perceptive, motor, and cognitive process. Neurophysiological studies on the mental representation of movement, modern neuroimaging techniques and developments in cognitive psychology have all contributed towards improving our understanding of the potential effects of rehabilitation on processes of plasticity and neuronal reorganization. The International Classification of Functioning, Disability and Health (ICF) promoted by the WHO, and the recent diffusion of family-centered models of healthcare have emphasized the importance of the ecological perspective with a view to providing effective therapies and a satisfactory quality of life for dystonic children and their families3. All these elements place the accent on the fact that we should not assess and treat the symptom alone. It is essential to examine how it influences fundamental functioning such as walking, manipulating objects, communication, independence in activities of daily living, and quality of life. Despite the considerable advances in the theoretical reference frame, interventions for dystonia in children are still heterogeneous and focus essentially on motor outcome or a specific adaptive function, while paying little attention to the child‟s complexity as an individual. As a result, even the most valid and sensitive tools for measuring outcome - in terms of the changes induced by a given treatment4- continue to concentrate exclusively on the neurofunctional aspects of the motor disorder, as well as revealing limitations in terms of their reliability5. 2.Currently-available outcome measures Given the numerous assessment scales available, here we describe only a selection of those used in the latest literature. They all start by measuring and classifying the severity of the condition, which is an inescapable element to consider in order to establish a realistically achievable outcome. The classifications used in the international literature concern postural kinetics and walking (the Gross Motor Function Classification System6 [GMFCS])and manual functions(the Manual Ability Classification System [MACS]7). The GMFCS distinguishes between five levels of severity: I. Walks without restriction. Limited in more advanced motor skills (running, jumping). II. Walks indoors without assistive devices. Limitations when walking outdoor or in the community. III. Walks with assistive devices, both indoors and out. Needs transportation when travelling long distances. IV. Cannot walk, not even with assistive devices. Needs assistance to move from sitting to standing. 2
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V. Self-mobility severely limited even with assistive devices. Unable to maintain antigravity of head and trunk. The MACS also distinguishes between five levels of severity: I. Handles objects easily and successfully. At most, limitations in the ease of performing manual tasks requiring speed and accuracy, but any limitations in manual abilities do not restrict independence in daily activities. II. Handles most objects, but with somewhat reduced quality and/or speed of achievement. Certain activities may be avoided or achieved with some difficulty; alternative ways of performing activities might be used, but manual abilities do not usually restrict independence in daily activities. III. Handles objects with difficulty; needs help to prepare and/or modify activities. Performance is slow and achieved with limited success regarding quality and quantity. Activities are performed independently if they have been set up or adapted. IV. Handles a limited selection of easily-managed objects in adapted situations. Performs parts of activities with effort and with limited success. Requires continuous support and assistance and/or adapted equipment to even partially complete the activity. V. Does not handle objects and has severely limited ability to perform even simple actions. Requires total assistance. After establishing a child‟s level of severity, more specific neurofunctional assessment scales are used.
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A. Posturokinetic functions • Gross Motor Performance Measure (GMPM) The GMPM 8 is a qualitative assessment tool with 20 items drawn from the Gross Motor Function Measure (GMFM)9. It focuses on the child‟s posture and movements, which are assessed on the grounds of 5 performance attributes: (1) postural alignment; (2) coordination (considering the direction, speed, strength, and amplitude of each motor sequence); (3) dissociated movements (isolated and independent movements); (4) postural stability; (5) weight transfer. This scale provides information on the structure of the child‟s movements, and is therefore sensitive enough to identify discrete changes even in severely disabled children. • Gross Motor Function Measure The GMFM is composed of 66 items grouped into 5 dimensions: 1. lying and rolling; 2. crawling and kneeling; 3. sitting; 4. standing; 5. walking, running, and jumping. Normal children are generally able to complete all the items, which are scored on a 4-point ordinal scale: 0 = the child does not initiate the item; 3
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1 = the child initiates the item (<10% of the maximum score); 2 = the child partially completes the item (>10, but <100% of the maximum score); 3 = the child completes the item. Each dimension contributes equally to the total score. Scores for each dimension are expressed as a percentage of the maximum score for the dimension in question. The total score is obtained by adding the scores for all five dimensions and dividing by five (the total number of dimensions). The GMFM was created to measure gross motor function quantitatively, disregarding the quality of the movements.
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B. Upper limb functions • The Melbourne scale It was developed in the early 1990s, validated in 1997 for children aged 5 to 15 years and recently revised for children aged 2 years 6 months to 15 years. 10 It is composed of items exploring different functional tasks, including reaching the mouth to eat, or grasping objects in different spatial directions. The Melbourne scale is particularly useful for examining selected actions, such as reaching for an object, grasping, releasing, manipulating, and reaching the mouth with the hand. The items are scored on a 4-point scale, based on pre-set criteria. They are intended to assess different aspects of upper limb function: some focus on the quality of the movements, including their range, precision, fluidity, and speed; others focus on the developmental level. The total score is expressed as a percentage obtained by dividing the sum of the scores for all the items by the maximum score, and multiplying by 100. The Melbourne scale is mainly useful for judging the magnitude of changes after medical or surgical treatment, or physiotherapy. It is worth bearing in mind that this tool focuses on motor activity, disregarding aspects such as cognition, language, or perception. It has proved very sensitive in measuring changes in performance over time in response to rehabilitation or pharmacological or surgical treatments. The drawback of this scale is that it can only be used for assessments on demand, providing no opportunity to observe and globally assess two-handed manual dexterity, which is more typical of the functional conditions of daily living. • Assisting Hand Assessment (AHA) This is a test recently developed to assess children with unilateral upper limb dysfunction 11 (and it is therefore useful in hemi-dystonic forms). It has been validated for children from 18 months to 12 years old. It is based on the acknowledgement of the different role of the two hands, and on the fact that the palsied hand does not necessarily have to be as skillful as the dominant hand in two-handed activities. The object is to assess not best performance, but habitual performance (disregarding the level of impairment). It is administered in the form of pre-set games demanding two-handed manipulation, which is rated on a scale of 1 to 4, where the general meanings are: 1 =„does not do‟; 2 = „ineffective‟; 3= „somewhat effective‟; and 4= „effective‟. The sum of the scores is converted into interval logit measures called AHA units, which range from 0 to 100 (where a higher measure indicates a greater ability). The items are divided into six categories: initiation/usage; arm use; grip-release functions; fine motor adjustments; coordination ability; performance pace. The test assesses habitual performance of the palsied hand in two-handed activities. It does not assess use of the hand on demand. It is organized hierarchically: the items become increasingly complex, based more on a gradual improvement in abilities than on age-dependent development. 4
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• The Besta scale Hand function can also be assessed using the assessment protocol for upper limb function developed by Fedrizzi 12. This scale was developed specifically to assess hemiparetic children. It is administered every six months and is composed of two different parts. First, grasping with the palsied hand is assessed using standardized material (three cubes, 0.5, 2, and 4 cm in size), and quantifying hand function on a 4-point scale:0= no grasping;1= hand grasping;2= tri-digital grasping;3= pincer grasping. Then, two-handed manipulation is quantitatively assessed, either during spontaneous play activity or using materials selected according to the child‟s age. The quality of the motor patterns is scored according to its variability or stereotypy: 0= the child does not use the impaired upper limb; 1=the child uses impaired limb (not hand) in a stereotyped pattern (wrist support) for holding; 2= the impaired hand cooperates in manipulation as a support (holding objects), albeit with a restricted number of stereotyped patterns; 3= the impaired hand cooperates in manipulation, carrying out simultaneous movements (both supporting and manipulating), and with a variable repertoire of motor patterns.
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C. Quantitative assessment of Movement Disorders Most studies associated the above-described neurofunctional scales with more specific scales measuring the severity of the movement disorder. In particular, the scales still used today for children with dystonia, although they were devised for adults, are: • The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) This is still one of the most often used scales, though it has been strongly criticized. It is divided into a Movement Scale and a Disability Scale13.The Movement Scale assesses nine body districts, each of which is awarded two scores, from 0 to 4: one score assesses provoking factors, i.e. what triggers the dystonic motor response; the other assesses its severity, i.e. the degree of invalidity caused by the dystonia in a given body district. The scale produces a total score ranging from 0 to 120.The Disability Scale assesses functions such as speech, writing, eating, hygiene, feeding, dressing, and walking. The BFMDRS was the prototype assessment tool, and was subsequently adapted for use in pediatric age, but it has shown a limited sensitivity for this age group on both its subscales. • Barry-Albright Dystonia Scale (BADS) The BADS14 has been much used, judging from the literature, especially for the purpose of monitoring the outcome of pharmacological and surgical interventions. It was originally devised for secondary dystonia, such as childhood cerebral palsy. It divides the body into eight districts, which are scored on severity based on two parameters, given as percentages, measuring the duration of the dystonia during an activity, and how much it interferes with the activity concerned. The minimum score for each body district is 0 (no dystonia), and the maximum is 4 (dystonia persisting for more than 50% of the time, and interfering with the function and a correct posture). This scale was originally designed for adults too, and has proved scarcely sensitive when applied to children.
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In recent years, however, the need to devise more specific scales for use in children, has led to the development of new scales.
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• The Movement Disorder-Childhood Rating Scale This scale was developed by the Stella Maris group in Pisa15 and stems from the precise need for an assessment tool specific for use in children. It is divided into two parts: General Assessment (Part I); and Movement Disorder Severity (Part II). Part I covers 4 areas - motor function, oral/verbal function, self-care, and attention/alertness - for a total of 15 items. By comparison with other assessment scales, it includes some additional items to better characterize the impact of movement disorders on different functions from a developmental perspective. In the motor function area, the items relate to head control, sitting and standing posture, and hand function. The oral/verbal function area includes an item assessing drooling because this is an important clinical sign in children with movement disorders. A completely new area has been added to explore attention and alertness, which are particularly vulnerable in developmental disorders and potentially sensitive to therapeutic interventions. Part II assesses the intensity of the prevalent movement abnormality in two conditions - at rest and during the performance of certain tasks - in seven body regions (eye and peri-orbital region, face, tongue and peri-oral region, neck, trunk, upper limb, and lower limb). The activities are performed after the child has received verbal instructions and a visual demonstration. All items are scored on a 5-point ordinal scale (0-4), where 0means no sign of abnormal function, and 4 means very severe problems. This scale has the particular merit of being able to assess the prevalent dyskinetic disorder and assign a separate score to all the dyskinetic components. Another of its qualities lies in that it enables both functional aspects and the clinical issue of severity to be assessed, then combined into a global score. The scale has proved useful in the clinical assessment of children, and it has been found particularly sensitive in identifying changes in children treated pharmacologically. • The Dyskinesia Impairment Scale This scale was developed by Monbaliu et al. 16specifically for the chronic forms of childhood cerebral palsy in order to assess the dystonic component separately from the choreo-athetosic component. It is consequently divided into two subscales, both of which assess 12 body regions: eyes, mouth, neck, trunk, limbs (upper and lower, further divided into proximal and distal, right and left). Dyskinesia characteristics can be assessed at rest and during activity and in terms of duration, amplitude, and influence on functional activities. Children are assessed using two scores - one in action (range 0-192); and one at rest (range 0-96) for a total score (combining the two subscales) ranging from 0 to 288. D. Scale for patient's individual goals Given the frequent reports in the literature of the currently-used scales having a limited sensitivity in measuring changes, they have been increasingly associated with new tools more “tailored” to individual patients that prove valid and reliable. Some of the most often used are as follows: • The Goal Attainment Scale (GAS) Awareness of the need for an integrated and family-centered approach supports the value of this tool in rehabilitation programs for neuromotor disorders of infancy. The GAS17 is a scale that establishes in advance the specific goals of treatment for a given child at a given stage of their development, in a given context and, most importantly, based on the child‟s and the family‟s 6
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particular needs. It therefore refers to an individualized criterion that is decided at the outset together with the child and family concerned. The goals are defined by means of 5 previouslyestablished points (five activities or functions) where: 0 represents the expected level of success; +1 or +2 represent levels higher than expected; and -1or -2 represent levels lower than expected. The GAS can be dichotomized as: goals achieved (scores 0, 1, 2)versus goals not achieved (scores -1 or -2). Each activity must be weighted, depending on the product of its importance to the patient and its difficulty. Many recently published works have reported on the utility of this scale in as much as it is sensitive in measuring even slight quantitative changes overlooked by traditional outcome measures, but are significant and clinically important for the child and his/her family. • The Canadian Occupational Performance Measure (COPM) The COPM18 is currently being used more and more. With a semistructured interview it enables the children or their parents to identify problems with performance in daily life in three settings: selfcare, productivity (at play and at school) and free time. These problems are scored on a scale from 1 to 10 (where 1 = not important, and 10 = very important), and the five most important problems are identified based on criteria of performance (“Can I complete this task?”) and satisfaction (“Am I satisfied with how I complete this task?”). The scale produces a measure of the efficacy of a treatment vis-à-vis the child‟s reported needs.
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E. Scales for assessing autonomy and functionality • The Functional Independence Measure for Children - WEEFIM This scale 19includes 19 items exploring six different developmental domains, including self-care, sphincter control, mobility, locomotion, communication, and social relationships. It is intended for children aged 6 months to 7 years. The items are scored on a 7-point scale, reflecting an increasing degree of independence and with respect to the need for assistance and assistive devices. • Pediatric Evaluation of Disability Inventory - PEDI Another internationally-adopted tool for assessing disability 20, this scale is intended for children aged 6 months to 7 years and 6 months . It comprises two different subscales: capabilities (which explores acquired functions), and performance (which assesses the degree of disability by measuring the level of assistance and the environmental modifications required). The Inventory is completed with the family‟s collaboration and takes about 45 minutes to administer.
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F. Scales for assessing quality of life Self- (or parent proxy-) perceived health-related quality of life (HRQOL) has recently emerged as a meaningful outcome measure in clinical trials and healthcare interventions. It can be particularly helpful not only in assessing the effectiveness of different therapeutic approaches, but also in guiding the medical staff‟s decision-making process. HRQOL assessment tools also provide an opportunity for parents and children to take an active part in decisions concerning the latter‟s treatment, in line with the modern family-centered model of healthcare21. Although the literature offers a growing number of valid generic and disease-specific HRQOL measures, they are still not homogeneous and they are rarely designed for children with dystonia.
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On the topic of pharmacological treatments,Tabbal 2 made the point that no exhaustive studies have been conducted in this field. Most of the currently-available drugs are off-label, and the reports published to date are based on extremely small and heterogeneous case series, and often on various outcome measures that have yet to be standardized. Briefly, the oral medication most often used for childhood dystonia is L-dopa, which remains the first choice at the onset of the motor disorder. If a month of therapy with L-dopa fails to produce results, the current guidelines recommend an anticholinergic agent (a controlled, double-blind clinical trial has only been conducted on trihexyphenidyl, which is useful when administered together with L-dopa). Other drugs used in clinical practice include: oral baclofen, long-acting benzodiazepine (clonazepam), carbamazepine, dopamine receptor antagonists (haloperidol and pimozide), and tetrabenazine. 2, 22, 23, 24, 25. As for the outcome measures used, a recent study by Battini et al.26 considered 68 patients with various motor disorders, divided into two age groups (0-3 and 4-18 years). They were assessed with the Movement Disorders Childhood Rating Scale (MDCRS) before treatment, and again after 6 months and after 12 months of treatment. Rather than to identify which pharmacological treatment was best for a given disorder, the aim of this study was to ascertain the sensitivity of the MDCRS in measuring changes induced by the treatment. The results seemed to confirm that, irrespective of the type of drug and the patient‟s age, an improvement was demonstrable in most cases (with the exception of the neurometabolic forms), and particularly in patients responding to Ldopa and in the myoclonic-dystonic forms. The improvement also appeared to be greater in the part of the scale measuring the functional aspects than in the part examining the severity of the dystonia. This brings us to the surgical options. Analyzing the report from by Romito et al.27 on the possible role of deep brain stimulation (DBS)- not only in primary forms of dystonia (for which its efficacy has already been amply documented), but also in secondary forms -what emerges is the growing need for valid and sensitive outcome measures capable of providing firm evidence of the efficacy of this type of treatment. The study was conducted on 15 accurately selected patients (only two of them under 18 years old) with static dystonia developing in pediatric age, assessed with the BFMDRS (Movement and Disability) 1-3 months after receiving DBS and then annually thereafter. The results demonstrated a real chance of improvement, even in the secondary forms, in terms not only of the severity of the dystonia, but also of the degree of disability, quality of life, and pain. Another important element that emerged from the work by Romito et al. concerns the timing of patient follow-up. Outcome measures are often studied and calibrated on trials with a very limited follow-up (up to 12 months), but it may take longer to document the treatment‟s efficacy over time. Keen et al.28conducted a study on 5 children with dyskinetic childhood cerebral palsy, who were a mean 11 years old at the time of undergoing DBS. They showed an improvement in their global scores on the BADS and BFMDRS-Movement, but the results were very contradictory when single items on the two scales were considered: the BADS identified a greater improvement in axial control, whereas the best results according to the BFMDRS-Movement were achieved in the area of language and the facial region. The poor clarity of these results underscores the problem of studies on small samples, as well as the limited sensitivity of the scales used to measure the quantitative and qualitative changes occurring after DBS. 8
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More encouraging findings on the efficacy of DBS in children with dystonia emerged from a study by Gimeno et al. 29, who used the Melbourne scale to examine the trend of responses to the treatment in the upper limbs. The study sample was divided into three groups: one included children with primary dystonia or dystonia-plus syndromes; another consisted of children with secondary dystonic forms; and the third was composed of children with dystonia related to progressive diseases. The Melbourne scale identified an improvement in the first and second groups, but not in the third, in which there was even a worsening dystonia in three cases. The limitations of this study, here again, concern the small sample size and short follow-up (at 6 and 12 months after DBS). In addition, the authors were critical of the Melbourne scale (despite its efficacy) because it selectively assesses the quality of limb movements, not their actual functionality. Starting with studies by Albright et al. in 200130, treatment with intrathecal baclofen(ITB) has been administered to children with both spastic and dystonic cerebral palsy. Most of the relevant studies 31, 32, 33 concerned children in GMFCS class IV-V, i.e. with severe symptoms. ITB treatment prompted no functional improvement in these samples, although all the authors of these studies emphasized that most of the children experienced an improvement in their dystonia sufficient to improve their posture and make it easier for caregivers to provide assistance. Lumsden et al.34administered a questionnaire to 273 children in an effort to bring out the main problems relating to their body functioning and structure, activities and participation, based on the ICF classification. The children were divided into four groups by the etiology of their dystonia (primary, secondary, hereditary-degenerative and primary-plus) and its severity (GMFCS).What emerged from the study findings is that the problem of pain affected all the groups, irrespective of the severity of their condition. Difficulties relating to daily living and manual praxis were reported mainly by the groups with secondary or primary-plus forms of dystonia, while problems with remaining seated were the main issue for the group with the more severe hereditary-degenerative forms. When the authors analyzed the literature, they identified 70 reports on different types of intervention/treatment, and confirmed once again that most of the neurosurgical studies had adopted scales that only quantified the severity of the dystonia (the BFMDRS and BADS),failing to consider other aspects that take priority for the children and their families, such as subjective improvements in the quality of their motor function. In one study, Gimeno et al.35 selected 6 children with severe dystonia (GMFCS level V; MACS level 4) treated with DBS. The authors found significant improvements in the pain scale and in the questionnaire on quality of life (CP Child questionnaire), and also on the COPM and GAS scales, which are designed not to quantify the severity of a child‟s condition, but the subjective quality of their motor function. Another prospective study by Gimeno et al.36 involved 30 patients between 3 and 18 years old who underwent DBS. Especially for secondary dystonia, it confirmed that assessing motor impairment (BFMDRS) is a very different matter from measuring functional goals (COPM): an improvement on the COPM did not always coincide with an improvement on the BFMDRS. This study confirmed yet again that holistic outcome measures are needed, so that assessments will also include profound issues relating to the autonomy and daily quality of life of children with dystonia and their families.
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4.Recommendations for the future • Use specific scales for pediatric age. • Consolidate the use of specific tools for the upper limbs and for practical activities, as already used for hemidystonic forms. • Include scales on quality of life and autonomy as outcome measures in clinical practice. • Use pain scales in particular: this symptom can be found in all the conditions in which motor disorders develop. • Adopt specific tools, suitable for a given child in a given family, for the child‟s particular disease and phase of development. It is important to have a toolbox of outcome measures and different generally-accepted scales capable of assessing different aspects of the dimensions of cerebral palsy in children. • In the light of findings in the literature, it also seems indispensable to identify other methods, taking the approach of evidence-based medicine (EBM),and using broad international databases in order to obtain more homogeneous populations of cases and sufficiently large samples on which to measure outcomes in relation to the various aspects and settings of the dystonic child‟s life.
Declaration of interest:
None of the authors declare any conflict of interest. The authors thank Frances Coburn (freelance science editor for scientific writing assistance)
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Unilateral Upper Limb Function Dev Med Child Neurol 2014; 56(7):665-672. 11) Krumlinde-Sundholm L, Hollmefur M, Kottorp A, Eliasson AC. The Assisting Hand Assessment: current evidence of validity, reliability and responsiveness to change. Dev Med Child Neurol 2007; 49: 259-264. 12) Fedrizzi E. I Disordini dello Sviluppo Motorio: Fisiopatologia- Valutazione diagnostica- Quadri clinici- Riabilitazione Piccin Eds, 2009. 13) Burke RE, Fahn S, Marsden CD, et al. Validity and reliability of a rating scale for the primary torsion dystonias. Neurology 1985; 35(1): 73-77. 14) Barry MJ, Van Swearingen JM , Albright AL. Reliability and responsiveness of the BarryAlbright Dystonia Scale. Dev Med Child Neurol 1999; 41(6): 404-411. 15) Battini R , Sgandurra G, Petacchi E, et al. Movement Disorder-Childhood Rating Scale: Reliability and ValidityPediatr Neurol 2008; 39(4): 259–265. 16) Monbaliu E, Ortibus E , De Cat J, et al. The Dyskinesia Impairment Scale: a new instrument to measure dystonia and choreoathetosis in dyskinetic cerebral palsy. Dev Med Child Neurol 2012; 54(3): 278-283. 17) Lynne Turner-Stokes. Goal Attainment Scaling (GAS) in Rehabilitation: a practical guide. Clin Rehabil 2009; 23 (4): 362-370. 18) Law M, Baptiste S, McColl M, et al. The Canadian occupational performance measure: an outcome measure for occupational therapy. Can J Occup Ther 1990; 57(2): 82-87. 19) Msall ME, Di Gaudio K, Rogers BT, et al . The functional independence measure for children (WeeFIM): Conceptual basis and pilot use in children with developmental disabilities. Clin Pediatr 1994; 33: 421-430. 20) Haley SM, Coster WJ, Ludlow LH, et al. Pediatric Evaluation of Disability Inventory (PEDI). Development Standardization and Administration Manual Boston, MA: Trustees of Boston University, 1992. 21) Shelly A, Davis E, Waters E, et al 2008The relationship between quality of life and functioning for children with cerebral palsy. Dev Med Child Neurol 2008; 50(3):199-203. 22) Jankovic J. Treatment of dystonia. Lancet Neurol 2006; 5(10): 864-872. 23) Bronte-Stewart H, Taira T, Valldeoriola F, et al. Inclusion and exclusion criteria for DBS in dystonia. Mov Disord 2011; 26 Suppl 1:S5-16. 24) Roubertie A, Roze E, Bahi-Buisson N, et al. Traitement des dystonies de l‟enfant. Arch Pediatr 2010; 17: 540-553. 25) EFNS guidelines on diagnosis and treatment of primary dystonias. Eur J Neurol 2011; 18(1):518. 26) Battini R, Olivieri I, Di Pietro R, et al. Movement Disorder-Childhood Rating Scale: a sensitive tool to evaluate movement disorders. Pediatr Neurol 2015; 53(1): 73-77. 27) Romito LM, Zorzi G, Marras EC, et al. Pallidal stimulation for acquired dystonia due to cerebral palsy: beyond 5 years. Eur J Neurol 2015; 22 (3): 426–433. 29) Keen JR, Przekop A, Olaya JE, Zouros A, Hsu FP. Deep brain stimulation for the treatment of dystonic cerebral palsy. J Neurosurg Pediatr 2014; 14(6):585–593. 30) Gimeno H, Lumsden D, Gordon A, et al. Improvement in upper limb function in children with dystonia following deep brain stimulation. Eur J Paediatr Neurol 2013; 17(4): 353-360. 31) Albright AL, Barry MJ, Shafton DH, Ferson SS. Intrathecal baclofen for generalized dystonia. Dev Med Child Neurol 2001; 43 (10): 652-657. 32) Motta F, Stignani C, Antonello CE. Upper limb function after intrathecal baclofen treatment in 11
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children with cerebral palsy. J Pediatr Orthop 2008; 28 (1): 91-96. 33) Motta F, Stignani C, Antonello CE. Effect of intrathecal baclofen on dystonia in children with cerebral palsy and the use of functional scales. J Pediatr Orthop 2008 ; 28 (2): 213-217. 34) Overgard TM, Kjaersgaard-Hansen L, Soe M, Illum NO. Positive experience with intrathecal baclofen treatment in children with severe cerebral palsy. Dan Med J 2015; 62(1): A4999. 35) Lumsden DE, Gimeno H, Tustin K, Kaminska M, Lin JP. Interventional studies in childhood dystonia do not address the concerns of children and their carers. Eur J Paediatr Neurol 2015; 19 (3): 327-336. 36) Gimeno H, Tustin K, Selway R, Lin JP. Beyond the Burke-Fahn-Marsden Dystonia Rating Scale: deep brain stimulation in childhood secondary dystonia. Eur J Paediatr Neurol 2012; 16 (5): 501-508.
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ACCEPTED MANUSCRIPT HIGHLIGHTS -The huge contribution of advances in the pediatric neurosciences, improvements in clinical practice, and new therapeutic options, has led to the development of new models of treatment and rehabilitation for movement disorders in childhood -Despite these advances, the assessment and treatment of patient are still not well defined in relation to the complexity of this disorder and to the difficulty in measuring it
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-The aim of the present study is to make a review of the outcome measures (available at the present time) in order to find the ones that are more reliable to assess the following items: natural history, neuro-functional impairment and responsiveness of treatment
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-In accordance with this review it is necessary to have a "toolbox" of the outcome measures capable of assessing various aspects and dimensions of life in children with different severity levels and clinical pictures of the condition .
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S1090-3798(17)31694-X
DOI:
10.1016/j.ejpn.2018.01.014
Reference:
YEJPN 2369
To appear in:
European Journal of Paediatric Neurology
Received Date: 31 May 2017 Revised Date:
11 January 2018
Accepted Date: 16 January 2018
Please cite this article as: Pagliano E, Baranello G, Masson R, Foscan M, Arnoldi MT, Marchi A, Aprile G, Pantaleoni C, OUTCOME measures for children with movement disorders, European Journal of Paediatric Neurology (2018), doi: 10.1016/j.ejpn.2018.01.014. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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OUTCOME MEASURES FOR CHILDREN WITH MOVEMENT DISORDERS Emanuela Pagliano, Giovanni Baranello, Riccardo Masson, Maria Foscan, Maria Teresa Arnoldi, Alessia Marchi, Giorgia Aprile, Chiara Pantaleoni
Corresponding Author: Emanuela Pagliano
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Developmental Neurology Unit, C. Besta Neurological Institute Foundation, Milan, Italy Via Celoria 11, 20133 - Milan, Italy
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Tel.: + 39 02 2394.2219 Fax: + 39 02 23942176
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e-mail: [email protected]
ACCEPTED MANUSCRIPT OUTCOME MEASURES FOR CHILDREN WITH MOVEMENT DISORDERS Emanuela Pagliano, Giovanni Baranello, Riccardo Masson, Maria Foscan, Maria Teresa Arnoldi, Alessia Marchi, Giorgia Aprile, Chiara Pantaleoni.
1. Introduction
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ABSTRACT The huge contribution of advances in the pediatric neurosciences, improvements in clinical practice, and new therapeutic options, has led to the development of new models of treatment and rehabilitation for dystonia in the last decade. It is now generally agreed that a multidimensional therapeutic approach is needed for children with motor disorders, whose motor function - conceived as a complex perceptive, motor and cognitive process - is impaired at a crucial time in their development, with a fallout on how their various adaptive functions evolve. Neurophysiological studies, modern neuroimaging techniques, and advances in cognitive psychology have all contributed to improving our understanding of the potential effects of treatments in early age - not only on the symptoms, but also on plasticity processes and neuronal reorganization. The International Classification of Functioning, Disability and Health (ICF) promoted by the WHO, and the diffusion of family-centered models of healthcare have underscored the importance of the ecological perspective with a view to providing effective therapies and a satisfactory quality of life for dystonic children and their families. The advances made in this area have made it necessary to study and developmore appropriate treatment outcome measures. In the light of these aspects, there is still not enough literature on the generally-accepted, exhaustive dystonia assessment tools. Given these limits, it might be useful to discuss the strengths and weaknesses of the main tools currently used in this setting.
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It is extremely difficult to define outcome measures for children with movement disorders. A recent work by Bertucco (2015)1confirmed that the clinical picture of dystonia is more complex in children than in adults, for a number of reasons: • first of all, there is a different etiopathogenesis and a different natural history of the disorders associated with dystonia, from childhood cerebral palsy (which is still the most common) to the genetic, metabolic and degenerative forms; • the early onset of the disorder can interfere with the acquisition of typical motor skills during critical periods of learning and skill development; • the great variety of signs and symptoms involved: different motor disorders often coexist (dystonic postures and movements, chorea and athetosis, and so on), and may be further complicated – especially in the secondary forms - by an associated spastic component (in the socalled “mixed form”); • the changeability over time in the way symptoms evolve, even in the natural history of the same form; • the intrinsic correlation of the motor disorder with perceptive, sensory, cognitive, emotional and communicational-relational problems, which are absolutely interdependent; • and finally - an important aspect especially in terms of rehabilitation - the pathological signs in dyskinetic children are often the result not only of damage to one or more systems controlling 1
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motor behavior, but also of strategies and compensatory mechanisms adopted over time to obtain a functional advantage.
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In addition to this clinical complexity, there is also the problem of how to choose the most appropriate therapeutic strategies. The most important treatments currently available are rehabilitation, pharmacological therapies, botulinum toxin injections (in focal forms), and surgical options such as intrathecal baclofen (ITB), and deep brain stimulation (DBS), and their efficacy needs to be measured and compared 1,2. Finally, a crucial aspect of any treatment and any measurement -particularly evident in this broad group of disorders – concerns patient outcome. What types of outcome can we measure? What is the ideal outcome for a given child with a given disorder, and at what stage of their development? The progress made by the neurosciences, and the consequent development of new rehabilitation methods have confirmed the need for a multidimensional approach to treatment dystonic children, conceiving their motor function as a perceptive, motor, and cognitive process. Neurophysiological studies on the mental representation of movement, modern neuroimaging techniques and developments in cognitive psychology have all contributed towards improving our understanding of the potential effects of rehabilitation on processes of plasticity and neuronal reorganization. The International Classification of Functioning, Disability and Health (ICF) promoted by the WHO, and the recent diffusion of family-centered models of healthcare have emphasized the importance of the ecological perspective with a view to providing effective therapies and a satisfactory quality of life for dystonic children and their families3. All these elements place the accent on the fact that we should not assess and treat the symptom alone. It is essential to examine how it influences fundamental functioning such as walking, manipulating objects, communication, independence in activities of daily living, and quality of life. Despite the considerable advances in the theoretical reference frame, interventions for dystonia in children are still heterogeneous and focus essentially on motor outcome or a specific adaptive function, while paying little attention to the child‟s complexity as an individual. As a result, even the most valid and sensitive tools for measuring outcome - in terms of the changes induced by a given treatment4- continue to concentrate exclusively on the neurofunctional aspects of the motor disorder, as well as revealing limitations in terms of their reliability5. 2.Currently-available outcome measures Given the numerous assessment scales available, here we describe only a selection of those used in the latest literature. They all start by measuring and classifying the severity of the condition, which is an inescapable element to consider in order to establish a realistically achievable outcome. The classifications used in the international literature concern postural kinetics and walking (the Gross Motor Function Classification System6 [GMFCS])and manual functions(the Manual Ability Classification System [MACS]7). The GMFCS distinguishes between five levels of severity: I. Walks without restriction. Limited in more advanced motor skills (running, jumping). II. Walks indoors without assistive devices. Limitations when walking outdoor or in the community. III. Walks with assistive devices, both indoors and out. Needs transportation when travelling long distances. IV. Cannot walk, not even with assistive devices. Needs assistance to move from sitting to standing. 2
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V. Self-mobility severely limited even with assistive devices. Unable to maintain antigravity of head and trunk. The MACS also distinguishes between five levels of severity: I. Handles objects easily and successfully. At most, limitations in the ease of performing manual tasks requiring speed and accuracy, but any limitations in manual abilities do not restrict independence in daily activities. II. Handles most objects, but with somewhat reduced quality and/or speed of achievement. Certain activities may be avoided or achieved with some difficulty; alternative ways of performing activities might be used, but manual abilities do not usually restrict independence in daily activities. III. Handles objects with difficulty; needs help to prepare and/or modify activities. Performance is slow and achieved with limited success regarding quality and quantity. Activities are performed independently if they have been set up or adapted. IV. Handles a limited selection of easily-managed objects in adapted situations. Performs parts of activities with effort and with limited success. Requires continuous support and assistance and/or adapted equipment to even partially complete the activity. V. Does not handle objects and has severely limited ability to perform even simple actions. Requires total assistance. After establishing a child‟s level of severity, more specific neurofunctional assessment scales are used.
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A. Posturokinetic functions • Gross Motor Performance Measure (GMPM) The GMPM 8 is a qualitative assessment tool with 20 items drawn from the Gross Motor Function Measure (GMFM)9. It focuses on the child‟s posture and movements, which are assessed on the grounds of 5 performance attributes: (1) postural alignment; (2) coordination (considering the direction, speed, strength, and amplitude of each motor sequence); (3) dissociated movements (isolated and independent movements); (4) postural stability; (5) weight transfer. This scale provides information on the structure of the child‟s movements, and is therefore sensitive enough to identify discrete changes even in severely disabled children. • Gross Motor Function Measure The GMFM is composed of 66 items grouped into 5 dimensions: 1. lying and rolling; 2. crawling and kneeling; 3. sitting; 4. standing; 5. walking, running, and jumping. Normal children are generally able to complete all the items, which are scored on a 4-point ordinal scale: 0 = the child does not initiate the item; 3
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1 = the child initiates the item (<10% of the maximum score); 2 = the child partially completes the item (>10, but <100% of the maximum score); 3 = the child completes the item. Each dimension contributes equally to the total score. Scores for each dimension are expressed as a percentage of the maximum score for the dimension in question. The total score is obtained by adding the scores for all five dimensions and dividing by five (the total number of dimensions). The GMFM was created to measure gross motor function quantitatively, disregarding the quality of the movements.
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B. Upper limb functions • The Melbourne scale It was developed in the early 1990s, validated in 1997 for children aged 5 to 15 years and recently revised for children aged 2 years 6 months to 15 years. 10 It is composed of items exploring different functional tasks, including reaching the mouth to eat, or grasping objects in different spatial directions. The Melbourne scale is particularly useful for examining selected actions, such as reaching for an object, grasping, releasing, manipulating, and reaching the mouth with the hand. The items are scored on a 4-point scale, based on pre-set criteria. They are intended to assess different aspects of upper limb function: some focus on the quality of the movements, including their range, precision, fluidity, and speed; others focus on the developmental level. The total score is expressed as a percentage obtained by dividing the sum of the scores for all the items by the maximum score, and multiplying by 100. The Melbourne scale is mainly useful for judging the magnitude of changes after medical or surgical treatment, or physiotherapy. It is worth bearing in mind that this tool focuses on motor activity, disregarding aspects such as cognition, language, or perception. It has proved very sensitive in measuring changes in performance over time in response to rehabilitation or pharmacological or surgical treatments. The drawback of this scale is that it can only be used for assessments on demand, providing no opportunity to observe and globally assess two-handed manual dexterity, which is more typical of the functional conditions of daily living. • Assisting Hand Assessment (AHA) This is a test recently developed to assess children with unilateral upper limb dysfunction 11 (and it is therefore useful in hemi-dystonic forms). It has been validated for children from 18 months to 12 years old. It is based on the acknowledgement of the different role of the two hands, and on the fact that the palsied hand does not necessarily have to be as skillful as the dominant hand in two-handed activities. The object is to assess not best performance, but habitual performance (disregarding the level of impairment). It is administered in the form of pre-set games demanding two-handed manipulation, which is rated on a scale of 1 to 4, where the general meanings are: 1 =„does not do‟; 2 = „ineffective‟; 3= „somewhat effective‟; and 4= „effective‟. The sum of the scores is converted into interval logit measures called AHA units, which range from 0 to 100 (where a higher measure indicates a greater ability). The items are divided into six categories: initiation/usage; arm use; grip-release functions; fine motor adjustments; coordination ability; performance pace. The test assesses habitual performance of the palsied hand in two-handed activities. It does not assess use of the hand on demand. It is organized hierarchically: the items become increasingly complex, based more on a gradual improvement in abilities than on age-dependent development. 4
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• The Besta scale Hand function can also be assessed using the assessment protocol for upper limb function developed by Fedrizzi 12. This scale was developed specifically to assess hemiparetic children. It is administered every six months and is composed of two different parts. First, grasping with the palsied hand is assessed using standardized material (three cubes, 0.5, 2, and 4 cm in size), and quantifying hand function on a 4-point scale:0= no grasping;1= hand grasping;2= tri-digital grasping;3= pincer grasping. Then, two-handed manipulation is quantitatively assessed, either during spontaneous play activity or using materials selected according to the child‟s age. The quality of the motor patterns is scored according to its variability or stereotypy: 0= the child does not use the impaired upper limb; 1=the child uses impaired limb (not hand) in a stereotyped pattern (wrist support) for holding; 2= the impaired hand cooperates in manipulation as a support (holding objects), albeit with a restricted number of stereotyped patterns; 3= the impaired hand cooperates in manipulation, carrying out simultaneous movements (both supporting and manipulating), and with a variable repertoire of motor patterns.
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C. Quantitative assessment of Movement Disorders Most studies associated the above-described neurofunctional scales with more specific scales measuring the severity of the movement disorder. In particular, the scales still used today for children with dystonia, although they were devised for adults, are: • The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) This is still one of the most often used scales, though it has been strongly criticized. It is divided into a Movement Scale and a Disability Scale13.The Movement Scale assesses nine body districts, each of which is awarded two scores, from 0 to 4: one score assesses provoking factors, i.e. what triggers the dystonic motor response; the other assesses its severity, i.e. the degree of invalidity caused by the dystonia in a given body district. The scale produces a total score ranging from 0 to 120.The Disability Scale assesses functions such as speech, writing, eating, hygiene, feeding, dressing, and walking. The BFMDRS was the prototype assessment tool, and was subsequently adapted for use in pediatric age, but it has shown a limited sensitivity for this age group on both its subscales. • Barry-Albright Dystonia Scale (BADS) The BADS14 has been much used, judging from the literature, especially for the purpose of monitoring the outcome of pharmacological and surgical interventions. It was originally devised for secondary dystonia, such as childhood cerebral palsy. It divides the body into eight districts, which are scored on severity based on two parameters, given as percentages, measuring the duration of the dystonia during an activity, and how much it interferes with the activity concerned. The minimum score for each body district is 0 (no dystonia), and the maximum is 4 (dystonia persisting for more than 50% of the time, and interfering with the function and a correct posture). This scale was originally designed for adults too, and has proved scarcely sensitive when applied to children.
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In recent years, however, the need to devise more specific scales for use in children, has led to the development of new scales.
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• The Movement Disorder-Childhood Rating Scale This scale was developed by the Stella Maris group in Pisa15 and stems from the precise need for an assessment tool specific for use in children. It is divided into two parts: General Assessment (Part I); and Movement Disorder Severity (Part II). Part I covers 4 areas - motor function, oral/verbal function, self-care, and attention/alertness - for a total of 15 items. By comparison with other assessment scales, it includes some additional items to better characterize the impact of movement disorders on different functions from a developmental perspective. In the motor function area, the items relate to head control, sitting and standing posture, and hand function. The oral/verbal function area includes an item assessing drooling because this is an important clinical sign in children with movement disorders. A completely new area has been added to explore attention and alertness, which are particularly vulnerable in developmental disorders and potentially sensitive to therapeutic interventions. Part II assesses the intensity of the prevalent movement abnormality in two conditions - at rest and during the performance of certain tasks - in seven body regions (eye and peri-orbital region, face, tongue and peri-oral region, neck, trunk, upper limb, and lower limb). The activities are performed after the child has received verbal instructions and a visual demonstration. All items are scored on a 5-point ordinal scale (0-4), where 0means no sign of abnormal function, and 4 means very severe problems. This scale has the particular merit of being able to assess the prevalent dyskinetic disorder and assign a separate score to all the dyskinetic components. Another of its qualities lies in that it enables both functional aspects and the clinical issue of severity to be assessed, then combined into a global score. The scale has proved useful in the clinical assessment of children, and it has been found particularly sensitive in identifying changes in children treated pharmacologically. • The Dyskinesia Impairment Scale This scale was developed by Monbaliu et al. 16specifically for the chronic forms of childhood cerebral palsy in order to assess the dystonic component separately from the choreo-athetosic component. It is consequently divided into two subscales, both of which assess 12 body regions: eyes, mouth, neck, trunk, limbs (upper and lower, further divided into proximal and distal, right and left). Dyskinesia characteristics can be assessed at rest and during activity and in terms of duration, amplitude, and influence on functional activities. Children are assessed using two scores - one in action (range 0-192); and one at rest (range 0-96) for a total score (combining the two subscales) ranging from 0 to 288. D. Scale for patient's individual goals Given the frequent reports in the literature of the currently-used scales having a limited sensitivity in measuring changes, they have been increasingly associated with new tools more “tailored” to individual patients that prove valid and reliable. Some of the most often used are as follows: • The Goal Attainment Scale (GAS) Awareness of the need for an integrated and family-centered approach supports the value of this tool in rehabilitation programs for neuromotor disorders of infancy. The GAS17 is a scale that establishes in advance the specific goals of treatment for a given child at a given stage of their development, in a given context and, most importantly, based on the child‟s and the family‟s 6
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particular needs. It therefore refers to an individualized criterion that is decided at the outset together with the child and family concerned. The goals are defined by means of 5 previouslyestablished points (five activities or functions) where: 0 represents the expected level of success; +1 or +2 represent levels higher than expected; and -1or -2 represent levels lower than expected. The GAS can be dichotomized as: goals achieved (scores 0, 1, 2)versus goals not achieved (scores -1 or -2). Each activity must be weighted, depending on the product of its importance to the patient and its difficulty. Many recently published works have reported on the utility of this scale in as much as it is sensitive in measuring even slight quantitative changes overlooked by traditional outcome measures, but are significant and clinically important for the child and his/her family. • The Canadian Occupational Performance Measure (COPM) The COPM18 is currently being used more and more. With a semistructured interview it enables the children or their parents to identify problems with performance in daily life in three settings: selfcare, productivity (at play and at school) and free time. These problems are scored on a scale from 1 to 10 (where 1 = not important, and 10 = very important), and the five most important problems are identified based on criteria of performance (“Can I complete this task?”) and satisfaction (“Am I satisfied with how I complete this task?”). The scale produces a measure of the efficacy of a treatment vis-à-vis the child‟s reported needs.
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E. Scales for assessing autonomy and functionality • The Functional Independence Measure for Children - WEEFIM This scale 19includes 19 items exploring six different developmental domains, including self-care, sphincter control, mobility, locomotion, communication, and social relationships. It is intended for children aged 6 months to 7 years. The items are scored on a 7-point scale, reflecting an increasing degree of independence and with respect to the need for assistance and assistive devices. • Pediatric Evaluation of Disability Inventory - PEDI Another internationally-adopted tool for assessing disability 20, this scale is intended for children aged 6 months to 7 years and 6 months . It comprises two different subscales: capabilities (which explores acquired functions), and performance (which assesses the degree of disability by measuring the level of assistance and the environmental modifications required). The Inventory is completed with the family‟s collaboration and takes about 45 minutes to administer.
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F. Scales for assessing quality of life Self- (or parent proxy-) perceived health-related quality of life (HRQOL) has recently emerged as a meaningful outcome measure in clinical trials and healthcare interventions. It can be particularly helpful not only in assessing the effectiveness of different therapeutic approaches, but also in guiding the medical staff‟s decision-making process. HRQOL assessment tools also provide an opportunity for parents and children to take an active part in decisions concerning the latter‟s treatment, in line with the modern family-centered model of healthcare21. Although the literature offers a growing number of valid generic and disease-specific HRQOL measures, they are still not homogeneous and they are rarely designed for children with dystonia.
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On the topic of pharmacological treatments,Tabbal 2 made the point that no exhaustive studies have been conducted in this field. Most of the currently-available drugs are off-label, and the reports published to date are based on extremely small and heterogeneous case series, and often on various outcome measures that have yet to be standardized. Briefly, the oral medication most often used for childhood dystonia is L-dopa, which remains the first choice at the onset of the motor disorder. If a month of therapy with L-dopa fails to produce results, the current guidelines recommend an anticholinergic agent (a controlled, double-blind clinical trial has only been conducted on trihexyphenidyl, which is useful when administered together with L-dopa). Other drugs used in clinical practice include: oral baclofen, long-acting benzodiazepine (clonazepam), carbamazepine, dopamine receptor antagonists (haloperidol and pimozide), and tetrabenazine. 2, 22, 23, 24, 25. As for the outcome measures used, a recent study by Battini et al.26 considered 68 patients with various motor disorders, divided into two age groups (0-3 and 4-18 years). They were assessed with the Movement Disorders Childhood Rating Scale (MDCRS) before treatment, and again after 6 months and after 12 months of treatment. Rather than to identify which pharmacological treatment was best for a given disorder, the aim of this study was to ascertain the sensitivity of the MDCRS in measuring changes induced by the treatment. The results seemed to confirm that, irrespective of the type of drug and the patient‟s age, an improvement was demonstrable in most cases (with the exception of the neurometabolic forms), and particularly in patients responding to Ldopa and in the myoclonic-dystonic forms. The improvement also appeared to be greater in the part of the scale measuring the functional aspects than in the part examining the severity of the dystonia. This brings us to the surgical options. Analyzing the report from by Romito et al.27 on the possible role of deep brain stimulation (DBS)- not only in primary forms of dystonia (for which its efficacy has already been amply documented), but also in secondary forms -what emerges is the growing need for valid and sensitive outcome measures capable of providing firm evidence of the efficacy of this type of treatment. The study was conducted on 15 accurately selected patients (only two of them under 18 years old) with static dystonia developing in pediatric age, assessed with the BFMDRS (Movement and Disability) 1-3 months after receiving DBS and then annually thereafter. The results demonstrated a real chance of improvement, even in the secondary forms, in terms not only of the severity of the dystonia, but also of the degree of disability, quality of life, and pain. Another important element that emerged from the work by Romito et al. concerns the timing of patient follow-up. Outcome measures are often studied and calibrated on trials with a very limited follow-up (up to 12 months), but it may take longer to document the treatment‟s efficacy over time. Keen et al.28conducted a study on 5 children with dyskinetic childhood cerebral palsy, who were a mean 11 years old at the time of undergoing DBS. They showed an improvement in their global scores on the BADS and BFMDRS-Movement, but the results were very contradictory when single items on the two scales were considered: the BADS identified a greater improvement in axial control, whereas the best results according to the BFMDRS-Movement were achieved in the area of language and the facial region. The poor clarity of these results underscores the problem of studies on small samples, as well as the limited sensitivity of the scales used to measure the quantitative and qualitative changes occurring after DBS. 8
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More encouraging findings on the efficacy of DBS in children with dystonia emerged from a study by Gimeno et al. 29, who used the Melbourne scale to examine the trend of responses to the treatment in the upper limbs. The study sample was divided into three groups: one included children with primary dystonia or dystonia-plus syndromes; another consisted of children with secondary dystonic forms; and the third was composed of children with dystonia related to progressive diseases. The Melbourne scale identified an improvement in the first and second groups, but not in the third, in which there was even a worsening dystonia in three cases. The limitations of this study, here again, concern the small sample size and short follow-up (at 6 and 12 months after DBS). In addition, the authors were critical of the Melbourne scale (despite its efficacy) because it selectively assesses the quality of limb movements, not their actual functionality. Starting with studies by Albright et al. in 200130, treatment with intrathecal baclofen(ITB) has been administered to children with both spastic and dystonic cerebral palsy. Most of the relevant studies 31, 32, 33 concerned children in GMFCS class IV-V, i.e. with severe symptoms. ITB treatment prompted no functional improvement in these samples, although all the authors of these studies emphasized that most of the children experienced an improvement in their dystonia sufficient to improve their posture and make it easier for caregivers to provide assistance. Lumsden et al.34administered a questionnaire to 273 children in an effort to bring out the main problems relating to their body functioning and structure, activities and participation, based on the ICF classification. The children were divided into four groups by the etiology of their dystonia (primary, secondary, hereditary-degenerative and primary-plus) and its severity (GMFCS).What emerged from the study findings is that the problem of pain affected all the groups, irrespective of the severity of their condition. Difficulties relating to daily living and manual praxis were reported mainly by the groups with secondary or primary-plus forms of dystonia, while problems with remaining seated were the main issue for the group with the more severe hereditary-degenerative forms. When the authors analyzed the literature, they identified 70 reports on different types of intervention/treatment, and confirmed once again that most of the neurosurgical studies had adopted scales that only quantified the severity of the dystonia (the BFMDRS and BADS),failing to consider other aspects that take priority for the children and their families, such as subjective improvements in the quality of their motor function. In one study, Gimeno et al.35 selected 6 children with severe dystonia (GMFCS level V; MACS level 4) treated with DBS. The authors found significant improvements in the pain scale and in the questionnaire on quality of life (CP Child questionnaire), and also on the COPM and GAS scales, which are designed not to quantify the severity of a child‟s condition, but the subjective quality of their motor function. Another prospective study by Gimeno et al.36 involved 30 patients between 3 and 18 years old who underwent DBS. Especially for secondary dystonia, it confirmed that assessing motor impairment (BFMDRS) is a very different matter from measuring functional goals (COPM): an improvement on the COPM did not always coincide with an improvement on the BFMDRS. This study confirmed yet again that holistic outcome measures are needed, so that assessments will also include profound issues relating to the autonomy and daily quality of life of children with dystonia and their families.
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4.Recommendations for the future • Use specific scales for pediatric age. • Consolidate the use of specific tools for the upper limbs and for practical activities, as already used for hemidystonic forms. • Include scales on quality of life and autonomy as outcome measures in clinical practice. • Use pain scales in particular: this symptom can be found in all the conditions in which motor disorders develop. • Adopt specific tools, suitable for a given child in a given family, for the child‟s particular disease and phase of development. It is important to have a toolbox of outcome measures and different generally-accepted scales capable of assessing different aspects of the dimensions of cerebral palsy in children. • In the light of findings in the literature, it also seems indispensable to identify other methods, taking the approach of evidence-based medicine (EBM),and using broad international databases in order to obtain more homogeneous populations of cases and sufficiently large samples on which to measure outcomes in relation to the various aspects and settings of the dystonic child‟s life.
Declaration of interest:
None of the authors declare any conflict of interest. The authors thank Frances Coburn (freelance science editor for scientific writing assistance)
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ACCEPTED MANUSCRIPT HIGHLIGHTS -The huge contribution of advances in the pediatric neurosciences, improvements in clinical practice, and new therapeutic options, has led to the development of new models of treatment and rehabilitation for movement disorders in childhood -Despite these advances, the assessment and treatment of patient are still not well defined in relation to the complexity of this disorder and to the difficulty in measuring it
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-The aim of the present study is to make a review of the outcome measures (available at the present time) in order to find the ones that are more reliable to assess the following items: natural history, neuro-functional impairment and responsiveness of treatment
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-In accordance with this review it is necessary to have a "toolbox" of the outcome measures capable of assessing various aspects and dimensions of life in children with different severity levels and clinical pictures of the condition .
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