Professor Orla Hardiman

Summary

Characterization of epidemiology, genetics and phenotype of ALS/MND in Ireland

Funding Agency

Health Research Board

Programme

CSA

Project Type

Clinician Scientist Award

Summary

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease. 70% of those with ALS die within 1000 days of their first symptom. Up to 50% of patients with ALS develop a degree of cognitive impairment, and 15 % develop a full-blown fronto-temporal dementia. There are currently no effective disease modifying therapies for ALS, and clinical intervention is focused on enhancing the quality of life for patients and relatives by relieving symptoms, providing emotional, psychological and spiritual support as needed, nd supporting the family in bereavement. As is the case for all neurodegenerative diseases, the generation of management protocols for ALS are more complex than for monophasic illnesses. This complexity relates to the multi-dimensionality and interdependence of required service provision. By extension, outcomes measurements must also be recognized as being multidimensional and interdependent. Notwithstanding their complexity, the design and availability of tools to determine and measure outcome in neurodegenerative conditions like ALS are of considerable importance. Such tools can be incorporated into the inception of integrated framework models of palliative care that can be planned, implemented, evaluated and reassessed. Design of such a framework requires detailed clinical information, drawn from a population based source that can then be validated in an incident based cohort monitored prospectively. As new disease modifying therapies become available, there is also an evolving need to identify key clinical milestones representing stages of ALS, to measure differences in resource utilization, and to define methods by which quality of life is measured across disease stages. These data are important for pharmaco-economic analyses of new therapeutics, and accurate analysis of these factors is also essential to the generation and monitoring of evidence based care pathway. This process is feasible in Ireland, as a national Register of ALS was established in 1995, and details of all incident cases (>1400) of ALS in the Republic of Ireland have been collected since then. Over 80% of all cases now attend the National ALS Centre in Beaumont Hospital. Retrospective data mining of the Register can provide important information about changes in incidence prevalence and natural history of the disease, the timing benefits and outcome of interventions including non-invasive ventilation and gastrostomy insertion; the beneficial effect of attending a multidisciplinary clinic, and the effects of cognitive impairment on prognosis and outcome. More detailed analysis from the more extensive clinic-based datasets can enrich the Register-based data to capture interactions with clinical professionals and the provision of equipment, and can incorporate phenotypic data including the presence and severity of cognitive impairment. These data can generate and validate prognostic indicators in ALS, from which a previously published staging algorithm can be replicated and validated. Prospective cohort analysis can then best used to generate and validate a framework of multidisciplinary intervention, including the appropriate intervention of general and specialist palliative care services The completed project will provide a best practice framework for future management of neurodegenerative disease, including an embedded rating scale that will trigger specialist palliative intervention in accordance with recent Irish health policy. The multidisciplinary research consortium comprises 6 key researchers from different fields, each with an established track record in their field of expertise, which include clinical care, population health , health services research and health economics. The research programme will be organised in three specific and interlinked work packages, spanning clinical, epidemiological and health services research including health economics.

Funding Agency

Health Research Board

Programme

Interdisciplinary Capacity Building Award

Summary