Abstract
Rett syndrome (RTT) is a severe neurodevelopmental disorder resulting in a wide range of functional impairments and therefore greatly impacts the lives of both patients and their families. While genetic and medical aspects have been studied for several decades, rehabilitation intervention research is still in its infancy. In this study, the investigating researchers have presented a rehabilitative framework by using music therapy for girls with RTT. This model is founded upon the use of music therapy in light of Stern’s proposal of subjective experience and affect attunement; it also refers to Rosenbaum’s family-centered rehabilitation medicine perspective. This study both describes the theory behind this intervention and presents a newly developed outcome measure. This novel tool may have future clinical and research applications. Music therapy for patients with RTT has not been well researched yet, and, as a result, is not universally recommended. However this study’s findings suggest that music therapy is an important component of multidisciplinary therapy. Further collaborative research should be encouraged in order to study and implement the use of music therapy in the treatment of severe disabilities. Projects such as the Enablin+ program with the support from the European Commission constitute fundamental tools in promoting integrative medical research and international networks.
Keywords
Introduction
Rett syndrome (RTT) is a complex disorder characterized by profound intellectual and multiple disabilities and is associated with health conditions such as epilepsy, scoliosis, respiratory, and gastrointestinal disorders [1–3]. Hand stereotypies also appear to be pervasive and prevent functional hand use [4–6]. Behavioral problems are some of the most burdening symptoms and emotional regulation is very low [7, 8]. Girls often present with teeth grinding, sleeping difficulties, screaming, anxiety or inappropriate fear, problems in mood regulation, crying and laughing during the night, mouth/tongue movements and facial grimacing, impulsivity and hyperactivity, as well as repetitive or self-injurious behavior [9].
Due to its complexity, rehabilitation of RTT must be multidisciplinary and should aim to improve both physical and mental health in the general framework of the bio-psycho-social model and of the International Classification of Functioning [10]. The recently published consensus guidelines [11] do not include music therapy (MT) in the evidence-based eligible interventions for RTT because of the insufficient reliability and replicability of the studies published in this regard. The main problems in this literature are due to the report of single cases or multiple single cases with low sample sizes [12] or to the use of not fully validated evaluation scales [13].
Chou et al. reported positive effects of MT incorporated into a multidisciplinary rehabilitation approach in a group of RTT patients, compared to a control group that followed a program based only on the usual multidisciplinary approach. MT did indeed improve receptive language, verbal and non-verbal communication skills, and social interaction for RTT patients [13]. However, not fully validated scales, or indicators having unclear sensitivity to detect change in RTT, such as the Rett Syndrome Clinical Severity Scale or the Rett Syndrome Motor Behavioral Assessment (MBA), have been used to measure the outcome. Recently a revised version of the MBA has been validated [14]. The scale is composed of 5 subscales: (i) motor dysfunction; (ii) functional skills; (iii) social skills; (iv) aberrant behavior; (v) respiratory behavior. While potentially useful, this instrument needs further validation checks (in particular regarding reliability and sensitivity) before it can be used as an outcome measure of MT in RTT.
Music therapy for girls with RTT
MT is a complex rehabilitative intervention with the general aim to establish, maintain and expand the intersubjective field [15, 16], and to also improve affective and social interaction, expression, and communication. The ultimate goal of MT is to support the developmental progression of the sense of self and individual integration [17]. In the clinical practice, MT has been used with different approaches for a long time in neurodevelopmental disorders. In 1943, in his seminal description of autism, Kanner reported the particular interest in music of these patients [18]. A recent systematic review of published studies on the effects of MT in neurodevelopmental disorders concluded that “a positive effect of improvisational MT was reported in most controlled studies (6/8) particularly in terms of social functioning with a higher response rate for the subgroup of patients with both autistic spectrum disorders (ASD) and intellectual disability (ID)” [19]. The Authors highlighted the importance of MT for children with ASD and ID but also recognized the need for more substantial studies analyzing other types of neurodevelopmental disorders.
Music therapy for RTT was first recommended by Andreas Rett himself [20], who recognized the capacity of music to penetrate the barrier of disability and severe intellectual impairment. Clinical reports describe how music promotes the motivation of girls with RTT to communicate and interact with their environment, and to develop cognitive and emotional skills [21, 22]. As observed by Hagberg, in RTT visual attention and non-verbal communication abilities (e.g., intense staring to obtain eye communication) are relatively preserved [23]. Girls with RTT are known to be very responsive to music and show behavioral modifiability. Eye contact, attention, emotional expressions, intentional vocal sounds may in fact improve during MT sessions, as reported by the description of cases that highlight an increase in communicative intentionality, eye contact, learning, and improved postural patterns [12, 25].
This study’s clinical model is founded upon D. Stern’s [17] concepts of developmental progression of the sense of self, integration, affect attunement, and change from a-modal to modal experience. The specific objectives of the intervention are: (i) promoting and supporting activation, containment, and communicative behavior; (ii) enhancing emotional competencies; (iii) promoting autonomy in interpersonal relationships and the desire to interact with the environment; (iv) preventing relational, emotional and communicative withdrawal; (v) supporting self-esteem; (vi) allowing patients to experience physical and mental relaxation.
The intervention with MT is mainly carried out through a process of “affect attunement”. This can be defined in terms of behaviors that express the quality of feeling of a shared affective state [17]. Intensity, timing, and shape are aspects of a person’s behavior that can be matched without imitating that individual [17]. “The concept of matching is one of the most valuable techniques” [26] in MT. “It is taking some kind of musical event and keeping some aspects of it the same in response and changing something” [15]. These non-verbal communications can be achieved in a MT setting through the technique of clinical improvisation. “This kind of inter-subjective matching, which we call affect attunement, is what happens in human interaction, and in the development of the relationship between parents and infants as well as therapists and clients. Probably the most necessary aspect of any successful therapy is that there is inter- subjective contact, i.e., a contact that two people can expand on” [15]. Thanks to affect attunement, the child can practice interpersonal exchange, participation, and sharing their own experience. This aspect is very important for the approach through MT in RTT given the presence of visual attention and non-verbal communication skills. Thus, as opposed to being an objective in and of itself in this intervention, affect attunement is one of the strategies that this investigation has used within its rehabilitative framework.
Normally, families are contacted with the proposal of 3 to 4 sessions to observe the girl’s behavior and interaction in a semi-standardized musical setting (see Table 1). Subsequently, individual MT sessions are planned (once a week for at least 10 months) and conducted in the same setting by the same therapist. Then multi-sensory communication is adopted to promote non-verbal expression with or without musical instruments. Girls are often placed at the piano with the aim of amplifying and enhancing through both acoustic and vibratory stimuli their involvement in multisensory communication. Furthermore, singing and sound reproduction activities that may include the use of AAC tools (e.g., communication objects/tools, picture communication symbols, tables, VOCA, E-TRAN) are encouraged. The clinical improvisation 1 technique of (through “matching” [26]) putting the girls at the grand piano to contain behaviors like hand stereotypies or muscle rigidity, exploits the phenomenon of body resonance in order to create a moment of relaxation and wellbeing. In the authors’ experience, some common characteristics are frequently observed in girls with RTT during MT sessions. These features include an immediate positive response to the MT intervention, good relational skills through multi-sensory channels, marked interest in the relationship with the therapist, and lowering of defenses during the MT intervention. A reduction of emotional instability/liability (influencing stereotypies, breathing and physical stiffness) and reduction of some difficulties in regulating the exploration of the environment have also been observed.
Description of the general intervention principles of MT in the study
Description of the general intervention principles of MT in the study
MT = Music therapy.
Italy has a well-established tradition of inclusion in schools for children with physical impairment or with profound intellectual multiple disabilities (PIMD) [3]. This tradition goes back to the 1970s, with the approval of a national Law (118/1971) on disability and the following Law 517/1977 and Law 104/1992, which stressed and regulated the inclusion in regular schools of children with disabilities (see the Supplementary Information). In the school year 2019-20 the students with certified disability (Law 104/92) represented 3.5% (almost 300,000) of the total number of students (from primary to upper secondary school), even though the percentage of children with multiple disabilities is not exactly known. 2 Almost all girls with RTT are regularly enrolled in early education and primary school. Starting from secondary school, these girls may be enrolled in special educational centers, wherever they are available.
The rehabilitative approach to complex disabilities in Italy is multimodal and multidisciplinary with the involvement of the family in all phases of rehabilitation. Rehabilitative services for children with PIMD are provided by public and private institutions through an accreditation system with the Regional Health Agency. The clinical services of the IRRCS Fondazione Don Carlo Gnocchi, Milan are accredited with this system. The Unit of Child Neurology and Psychiatry provides multidisciplinary ambulatory services for children with disability. Since the Foundation is both a health care center and a research institution, several European projects and collaborations have been implemented.
In 2014-2016, within the Leonardo Life Long Learning Programme, the European Commission funded the program Enablin+. The project sought to help health care services, professionals and parents’ associations across several European countries to communicate together, with the general objective of enhancing the quality of life of children with PIMD and intensive support needs. The aims of the project were: (i) to carry out a needs study through questionnaires filled out by professionals, families and care-givers; (ii) to describe good practices of intervention; (iii) to develop a set of training modules [27, 28]. The center for this study was the Italian partner of the project, and within this framework, a clinical intervention program was developed, based upon MT for girls with RTT, which is still employed. The Enablin+ program led to the development of an observational tool, which will be described in this article, to assess MT in girls with RTT.
In general, this intervention strategy is founded upon the coordinated action of a multidisciplinary team, which conducts a preliminary assessment through an ICF approach. Each child receives individualized care and a rehabilitation plan that is approved by the family after sharing the child’s needs. In the last 30 years, at least in the western world, the rehabilitative approach to complex disability has substantially changed. The possibility for health care providers to identify, measure, and understand the life experience of people with chronic health conditions and that of their families is now recognized. In this regard, the family-centered multidisciplinary approach to rehabilitation [29] takes into account both the patients and their family [30, 31]. The goal of the rehabilitation process is to improve the life condition of not only the patient but the entire family. The multidisciplinary intervention involves medical and psychological therapy, physiotherapy, speech therapy, augmented and alternative communication (AAC), and psychomotor activities. The rehabilitative team has also frequent meetings with external professionals, such as teachers or representatives from patient associations. In particular, the rehabilitation team meets the teachers’ team twice a year with the purpose of sharing the objectives of the educational and rehabilitative intervention plans. Written reports, participants’ observations and data collecting are routinely done by the team. In many rehabilitative centers MT has long been included as a possible support intervention in the multidisciplinary clinical programs for girls with RTT [32]. Since 2007 this view has also been embraced by rehabilitative services, even though MT is only accredited as an intervention for RTT in some regions of Italy.
Outcome measures
Rehabilitative approaches to RTT have not been standardized yet and rigorous research is needed to develop shared protocols and strategies, such as in the case of motor function [33, 34]. In a recent literature review, the scarcity of studies evaluating the outcomes of rehabilitation programs has been highlighted, and it has been recommended that patients with RTT follow a multidisciplinary program in order to preserve autonomy and to improve their quality of life [35]. In the literature, several outcome indicators have been put forward, which could be classified in experimental (exploratory) or truly clinically applicable measures.
Among experimental instruments, neurobiological measures (Brain Derived Neurotrophic Factor, BDNF) and activation of brain structures were documented by neuroimaging studies [36]. The effect of MeCP2 deficiency on neural circuitries has been extensively studied in animal models [37]. The main alterations found consist of functional changes in many forebrain structures (excitatory hypoconnectivity) and in the caudal brainstem (hyperconnectivity) [37]. While one of the consequences of impaired MeCP2 function is reduced production of Brain Derived Neurotrophic Factor (BDNF), it has been shown that an environmental enrichment treatment with these girls leads to increased BDNF levels 6 months after intervention [36]. This study could provide a useful reference also for future studies involving MT sessions with girls with RTT. The visuo-perceptive and auditory function is generally preserved in girls with RTT, even though there might be delayed auditory processing [11]. With the current state of research, it is difficult to hypothesize the specific neural effect of MT in girls with RTT. Nevertheless, the rationale for using music with these patients is provided by many studies that have investigated the effects of music on emotional circuits in control participants or in those with autistic spectrum disorders [38] (in a recent meta-analysis Koelsch reported 47 neuroimaging studies [39]). These studies highlighted that music can lead to the activation of the entire emotional/affective brain structures. According to Koelsch, music could engage sensory processes, perception, attention, and action, thus activating multiple brain structures involved in sensorimotor, cognitive, and emotional processing [40]. It follows that “the fact that music elicits changes in limbic and paralimbic brain structures opens up the possibility for application for music based therapies” [41]. In this sense, both experimental studies and neuroimaging studies, even if not directly feasible with girls with RTT, could be useful in the future to obtain further evidence correlating neurophysiological processes and emotional/cognitive processes that are activated during the MT sessions, whose clinical rationale is provided by contemporary developmental psychology theory [15]. In Table 2 the methods and the outcome measures used in the main studies on the MT intervention with girls with RTT are described.
Description of the main MT interventions for girls with RTT described in the literature
Description of the main MT interventions for girls with RTT described in the literature
In terms of clinically applicable measures, a comprehensive and objective evaluation of the rehabilitative outcome in MT for RTT has not been put forward yet. A coding scheme has been proposed by Raglio et al. [42], but is not easily transferable to the specificity of the clinical rehabilitation of RTT. Therefore, a new tool has been developed and applied to evaluate the harmonization of the person in the behavioral modalities of containment and activation in the MT setting [43] (see the Supplementary Information). From the perspective of this study, harmonization is a process that makes individual functioning flexible and competent as one interacts with their environment, leading to change from an archaic level to a more integrated one [44]. MT does not target specific functions, but rather the balance and homogeneity of functioning in a coordinated and integrated system. The observational and clinical tool that was developed [43] measures the clinical results and in principle could be used for girls with RTT, as well as children with PIMD in general. In collaboration with the family, the goal is to share the impact of the MT intervention on girls with RTT. This evaluation tool is intended to monitor the general evolution of MT sessions and register changes in specific expressive behavior (songs, sound dialogue). The observational tool is composed of two parts: 1) Song and sound dialogue and 2) Listening to music. Both parts are composed of two sections: activation and countenance, each of which contains observative assessment items. Possible values of the items range from 0 to 5, and the patient’s scores, for each section, are summarized through mean and variance. The average score provides a measure of the level of functioning, while the variance provides a general proxy of variability, harmonization and integration. To allow a global, integrated and complete description of each patient, a specific section is provided to insert qualitative comments or observations. It is worth observing that harmonization and the level of functioning can dissociate in the clinical practice and were indeed conceived as two separate factors (a low level of functioning with a high harmonization indicates an emotional well-being despite the severity of the disease). A comprehensive description of the observation tool is provided in Table 3.
Sections and items of the observational tool for MT used in our clinical centers
AL is a 10-year-old girl with MeCP-2 mutation of type c. 1063_1326 deletion 264 + insertion TGCG. At 8 months a delay in the achievement of motor milestones started. During the second year of life, she lost the use of her hands and the few words which she had already acquired. By the age of nine, she lost the ability to walk independently and can now only walk with one-hand support. The patient’s use of her hands is limited to touching and grasping with assistance, without holding objects. AL does not suffer from epilepsy, neither does she have breathing disturbances in the form of hyperventilation or apneas. The patient presents with daytime distress and agitation in addition to night agitation with frequent awakenings. Risperidone and Melatonin have been recently prescribed.
AL uses some Augmentative and Alternative Communication (AAC) strategies in order to communicate simple concepts. MT was prescribed, one session of 45 minutes a week, 19 months before the realization of the attached video clip (Supplementary Information), in addition to the usual care, due to the presence of behavior problems. AL is now able to interrupt stereotypies not only during the sessions but also during daily personal time when emotionally engaged in enjoyable activities at school or at home. Auditory attention improved as well as attention to tasks in which she is involved. Other noteworthy improvements are related to the desire to interact with the environment, to initiate interpersonal exchanges and to activate nonverbal communicative turns. Her mother says that behavior problems have slightly decreased.
Conclusion
In the current state of research, the use of MT for RTT seems supported by single-case studies [12] or by studies without control groups or with poor measurement of the outcome. A recent study by Chou et al. [13] highlighted a significant improvement in receptive language, verbal and non-verbal communication skills, and social interaction when MT is included in the usual multimodal interventions (physiotherapy, hydrotherapy, speech therapy, . . .). A fundamental shortcoming of that study is the adoption of non-validated indicators or scales not standardized in RTT.
In this essay a model has been described to employ MT in the treatment of girls with RTT and to monitor clinical changes. This model has been incorporated into the multidisciplinary rehabilitative framework adopted for treatment of complex disabilities such as RTT. A limitation of the present work is that the observation instrument described in the previous section is still not standardized, even though standardization in a multi-population setting may be a future development of new European programs with the same goals of the Enablin+ project [27, 28]. This will also allow researchers to assess the impact of MT on a large sample of girls with RTT.
In conclusion, further experimental and observational studies investigating the efficacy of MT in RTT are necessary and mandatory. Meanwhile, given the presence of a coherent theoretical framework in the context of developmental psychology supporting the use of MT in severe neurodevelopmental disorders, it is recommended that researchers continue investigating the clinical and neurophysiological implications of this therapy. In this regard, an action plan for the future involves the validation of the observation tool described in this essay, so that it can be reliably used in rehabilitative settings. The Anxiety and Depression Mood Scale (ADAMS) [45], which has already been applied in RTT [46], as well as the MBA (if further explored) [14] or other neurobiological/neurophysiological indices, could also be usefully added to the outcome evaluation methods. A hand functioning scale should also be considered in the study protocol [47]. As a future development, researchers associated with this study plan to validate this scale in a cohort of Italian children with intellectual disabilities. The study protocol could also include an evaluation questionnaire on family satisfaction [30] and on teachers’ perception of MT and other therapies administered in associated clinical centers.
Footnotes
Acknowledgments
The authors are very grateful to Mrs. Nagley Bertoldi Losa for her careful review of the manu-script. They are also very grateful to Riccardo Rijoff for his fundamental contribution in developing the observational protocol. This work has obtained the attention and approval of the European Life Long Learning Project Enablin + for the inclusion of young people with complex and intense support needs, Contract 541981-LLP-1-2013-1-BE-LEONARDO-LMP. Furthermore the authors would also like to thank the Promoter of this project, Prof. Jo Lebeer. This document reflects the views of the authors only. The Commission cannot be held responsible for any use that may be made with the information contained therein. The rehabilitative clinical model was presented as a Poster at the EACD (European Academy for Childhood Disabilities) Congress in Copenhagen, May 2015.
Enablin + has obtained funding from the European Life Long Learning Program for the inclusion of young people with complex and intense support needs, Contract 541981-LLP-1-2013-1-BE-LEONARDO-LMP
Conflict of interest
The Authors report no conflict of interest.
