Music Therapy Protocol to Support Bulbar and Respiratory Functions in ALS

This study evaluates potential of music therapy treatment to support breathing, speech, swallow and cough of persons with amyotrophic lateral sclerosis (ALS). Music therapy is the clinical use of music and its elements to enhance human health and wellbeing. Application of music therapy principles in neurorehabilitation allow to treat cognitive, sensory, and motor dysfunctions.

ALS clinical presentation and pathophysiology

Amyotrophic lateral sclerosis (ALS) is a group of rapidly progressive fatal neurological diseases involving the brain and spinal cord. Clinical presentation is phenotypically heterogeneous and depends on the type of onset. The pathophysiology mechanisms behind ALS are not clear and may include oxidative stress, protein misfolding and aggregation, skeletal muscle dysfunction, glutamate excitotoxicity, mitochondrial dysfunction, neuroinflammation, and apoptosis. Whilst in the past ALS was considered distinctly a disorder of the motor system, current evidence suggests that some cognitive (ALSci) or behavioural (ALSbi) impairment occurs in up to 50% of cases, and co-morbid dementia (ALS-FTD) occurs in approximately 14% of patients with a new diagnosis of ALS. The notion that "pure" ALS and "pure" FTD may present two extremes of one disease continuum is reinforced by identification of transactive response DNA-binding protein 43 (TDP-43) as a major pathological substrate underlying both diseases. Emotional lability (pseudobulbar affect), a symptom frequently correlated with bulbar involvement in ALS, may also be confusing and disruptive, especially when communicating with those who are not aware of the nature of the problem.

Music therapy potential in multidisciplinary model of ALS care

Considering the multiple and complex needs of people with ALS (PALS), the National Institute for Health and Care Excellence (UK) guideline \[NG42\] suggests coordinated care using a clinic based, specialist ALS multidisciplinary team approach. American Academy of Neurology recommends multidisciplinary team (MDT) model of care where patients are seen by a comprehensive team of health care professionals who each focus on specific health domains including walking, breathing, speaking, eating, activities of daily living, and psychosocial needs during one clinical visit. Multidisciplinary ALS care has been shown to increase survival of people with PALS and to improve their mental QoL.

More rehabilitation options have to be considered for PALS, enabling them to reach their fullest potential, delaying the disease progression and prolonging lifespan. Music therapy (MT) is the clinical use of music and its elements to accomplish individualized health goals within a therapeutic relationship. Music engages vast network of regions located in both hemispheres of the brain and shares processing components with other functions, such as those involved in language, movement, reasoning and experiencing emotions. Application of MT principles in neurorehabilitation allow to treat cognitive, sensory, and motor dysfunctions. Professionally trained music therapists are well equipped to provide symptomatic care for people with neurodegenerative diseases, adapting to increasing and changing disability of each patient as the disease progresses, whilst maintaining and developing trusting therapeutic relationship established early in the disease course. Albeit currently underused, MT could be one of the modalities of supportive rehabilitation in ALS.

Research on clinical MT applications for ALS is scarce and presents significant challenges due to heterogeneity of ALS clinical presentation and progression, poor scientific understanding of the disease mechanisms and the ethical issues of research involving terminally ill people. It has been suggested that MT could contribute to interdisciplinary ALS care. There is anecdotal evidence that MT increases mind-body connection, reduces distressing physical symptoms such as dyspnoea and pain, and associated feelings of loneliness, anxiety and sadness for patients with advanced ALS, is "pleasant and restorative" for PALS with tracheostomy and their families , and provides families affected by ALS with opportunities for shared meaningful activities. The first randomized controlled trial (RCT) of music therapy effect on people living with ALS found that active MT increased communication, improved QoL and decreased the physical symptoms of the disease for people with ALS during hospital stay. Music-assisted relaxation may be a useful strategy to optimize noninvasive ventilation (NIV) experience for people with ALS.

It may be concluded that, firstly, in most cases, MT is available for PALS at the end of life, when natural communication and motor functions are lost or limited, that music therapists are normally not included into multidisciplinary model of ALS care and that the predominant type of music intervention being used for treatment is music listening. Secondly, little research has been done to understand the effects of MT interventions conducted with patients at earlier stages of ALS and no published research addressing the use of MT techniques for neurorehabilitation (e.g. supporting motor, cognitive, respiratory, swallowing, speech functions) of PALS has been found.

Role of exercise in ALS treatment

Prior to recently the exercise has been discouraged for people with ALS, the recommendation based on the assumption that exercise can lead to muscle fatigue and, hence, increase patient's disability. This assumption however is not supported by scientific evidence, whilst, to the contrary, there is evidence that physical inactivity secondary to ALS may lead to cardiovascular deconditioning, disuse weakness and consequential muscle atrophy. Existing literature reviews support evidence for moderate exercise in ALS, whilst highlighting importance of supervised, individualized training programs. Cochrane review concluded there was no solid evidence to deem exercise in ALS beneficial or harmful and emphasized the need for further research. Recent data suggests that exercise may be beneficial for cellular and morphological adaptations in motor neuron function and thus may help to maintain motor function. Finally, preliminary results of a new RCT suggest that strictly monitored exercise programs reduce motor deterioration in ALS. Thus, in current clinical practice regular moderate exercise is encouraged for people with ALS to prolong mobility and independence.

MT for management of bulbar and respiratory symptoms in ALS

Even more so than in case of the general physical exercise, there is lasting controversy in regards to the role of exercise in management of bulbar and respiratory ALS symptoms. 93% of people with ALS experience speech impairments and 85% present with swallowing dysfunction at some point during the disease progression. Loss of natural communication is regarded by the patients as one of the worst aspects of the disease. Respiratory failure has been cited as the leading cause of death, and weakening of the respiratory function and adherence to NIV as the leading causes of anxiety of people with ALS. Patients with dysphagia reported social isolation, fear and decreased mental health. Dysphagia and malnutrition contribute to 25.9% of ALS mortality and increase the risk of death by 7.7 times. Aspiration pneumonia and dehydration have also been cited among the leading factors contributing to mortality in ALS.

Although there is lack of evidence supporting the use of strengthening exercises for improving speech in patients with ALS, there is no evidence of such exercises being harmful. Respiratory training may have positive effect on respiratory and swallowing functions of people with ALS. Whilst physical and psycho-emotional needs of people with ALS that MT can potentially attend to are many and varied, literature overview and empirical evidence suggest that researching the role of individualized, carefully monitored MT program to support respiratory and bulbar functions of people with ALS currently constitute the highest priority as these functions directly affect survival.

Study aim and significance

Applied MT research in multidisciplinary clinical context allows to systematically look at bulbar and respiratory functions support in ALS, which is important to do, since swallowing, vocalization and breathing are tightly coordinated, and close relationship exists between these processes, in terms of location and activation of the neurons.

This study intends to determine feasibility of a MT protocol as intervention to support respiration, cough, swallowing and speech functions of persons with amyotrophic lateral sclerosis (PALS). Since MT constitutes a new treatment modality for bulbar and respiratory dysfunction in ALS, the study is focused primarily on safety and tolerability of the treatment protocol.

Music therapy treatment protocol

Upper motor neurons and lower motor neurons deterioration in ALS results in dysarthria and dysphagia of spastic-flaccid type, although actual presentation varies in each patient and changes with the disease progression. Generally, lower motor neurone (LMN) involvement, characteristic of bulbar onset, leads to flaccid presentation, whilst degeneration of upper motor neurone (UMN), characteristic of spinal onset, results in spasticity of bulbar muscles. Muscle relaxation and moderate exercise, as well as learning efficient breathing and voice production techniques, voice care techniques and ALS-specific communication strategies may be helpful, rather than rigorous strengthening oral motor exercises. The protocol serves the following primary therapy objectives:

* to increase breath support,
* to increase muscle relaxation,
* to increase speech rate,
* to prevent / decrease hypernasality,
* to maintain swallowing coordination.

ALS-specific, individualized MT protocol was delivered to study participants in their homes twice weekly for the duration of six weeks by the researcher, who is a board certified music therapist and neurologic music therapist, with experience of working with this patient group and in this setting. Facilitating music structures have been composed by the researcher to support cueing, timing and intensity of breathing and vocalization exercises. These structures were regularly modified to suit the unique capabilities, current individual demands and progress of each participant. One familiar song, selected by the participant, was used for each participant in therapeutic singing exercise closing each session.

Data collection

Assessing bulbar dysfunction in ALS presents additional challenge to a researcher, as the existing tools may be not sensitive enough to reliably measure the change, given that ALS is a rapidly degenerating disease and that the rate of deterioration varies greatly from patient to patient. An array of subjective and objective measurements for bulbar and respiratory changes are used, including standard respiratory tools (FVC, MIP, MEP, PCF), videofluoroscopic swallow study, visual analogue scales for ease of speech and respiration, machine analysis of recorded vocal samples, semi-structured interviews and session descriptions, to explore the feasibility of systematic bulbar and respiratory assessment in ALS for future research.

Eligibility Criteria:
Inclusion Criteria:

* Newly diagnosed patients at ALS Centre Moscow (consecutive sampling)
* Diagnosis of probable or definite ALS by the revised El Escorial criteria confirmed by neurologist at ALS Moscow Centre prior to screening for enrollment.
* Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) bulbar subscore ≥ 9, but ≤ 11, where bulbar score=the sum of ALSFRS-R questions 1-3 (maximum score of 12)
* Forced vital capacity (FVC) greater than 60%
* Unimpaired cognition as evidenced by Edinburgh Cognitive and Behavioural ALS Screen (ECAS) cut-off scores adjusted for age and education
* Able to consent to treatment
* Native speakers of Russian

Exclusion Criteria:

* Tracheostomy or mechanical ventilation
* Diaphragmatic pacer
* Significant concurrent respiratory disease
* Allergies to barium
* Receiving any other experimental treatment for dysarthria, dysphagia, dystussia and dyspnoea for the duration of the study
* Receiving any other music therapy treatment for the duration of the study