Developments in the assessment of non-motor disease progression in amyotrophic lateral sclerosis

ABSTRACT

Introduction

The burden of non-motor symptoms is a major determinant of quality of life and outcome in amyotrophic lateral sclerosis (ALS) and has profound negative effect also on caregivers.

Areas covered

Non-motor symptoms in ALS include cognitive impairment, neurobehavioral symptoms, depression and anxiety, suicidal ideation, pain, disordered sleep, fatigue, weight loss and reduced appetite, and autonomic dysfunctions. This review summarizes the measures used for the assessment of non-motor symptoms and their properties and recaps the frequency and progression of these symptoms along the course of ALS.

Expert opinion

Non-motor symptoms in ALS represent a major component of the disease and span over several domains. These symptoms require a high level of medical attention and should be checked at each visit using ad hoc questionnaires and proactively treated. Several instruments assessing non-motor symptoms have been used in ALS. Specific screening questionnaires for non-motor symptoms can be used for monitoring patients during telehealth visits and for remote surveillance through sensors and apps installed on smartphones. Novel trials for non-motor symptoms treatment specifically designed for ALS are necessary to increase and refine the therapeutic armamentarium. Finally, scales assessing the most frequent and burdensome non-motor symptoms should be included in clinical trials.

KEYWORDS:

• Amyotrophic lateral sclerosis
• non-motor symptoms
• questionnaires
• cognition
• pain
• sleep
• fatigue
• autonomic dysfunction

Article highlights

• The burden of non-motor symptoms is a major determinant of quality of life and outcome in amyotrophic lateral sclerosis (ALS)

• Non-motor symptoms include, among the others, cognitive impairment, neurobehavioral symptoms, pain, disordered sleep, fatigue, depression and anxiety, suicidal ideation, weight loss and reduced appetite, and autonomic dysfunctions.

• Some of these symptoms are mediated by the reduction of mobility of limbs and trunk or to the impairment of bulbar function, while others are related to the diffusion of the pathological process to structures such as frontal and temporal cortices, hypothalamus, basal ganglia, and autonomic nervous system.

• Non-motor symptoms require a high level of attention by the health personnel, should be checked at each clinic visit or through telehealth contacts, both with direct inquiry and use of ad hoc questionnaires, and should be proactively treated

• These questionnaires should be also adapted and validated to be included in person-centered web-based and smartphone platforms

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interests

A Chiò serves on scientific advisory boards for Mitsubishi Tanabe, Roche, Biogen, Cytokinetic, Amylyx and Lilly. A Calvo has received research grant from Cytokinetics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Additional information

Funding

This work was in part supported by the Italian Ministry of Health (Ministero della Salute, Ricerca Sanitaria Finalizzata, grant RF-2016-02362405), the European Commission’s Horizon 2020 Programme (grant agreement 101017598), the Italian Ministry of Education, University and Research (Progetti di Ricerca di Rilevante Interesse Nazionale, PRIN, grant 2017SNW5MB), the Joint Programme – Neurodegenerative Disease Research (ALS-Care, Strength and Brain-Mend projects), granted by the Italian Ministry of Education, University and Research. This study was performed under the Department of Excellence grant of the Italian Ministry of Education, University and Research to the ’Rita Levi Montalcini’ Department of Neuroscience, University of Torino, Italy.