Motor neuron disease in Ireland : epidemiology, risk factors and prognostic indicators

2019-11-22T18:24:11Z (GMT) by Orna O'Toole

This thesis describes a series of studies examining aspects of the epidemiology of motor neuron disease (MND). The Republic of Ireland has a unique database of all patients diagnosed with MND which allows detailed study of MND epidemiology over time. Approximately 200-240 patients in Ireland have MND at any one time and 80 patients are diagnosed on a yearly basis. Data on over 1000 patients has been collected since 1993. The Irish population is an ideal study group for analysis as we are a small island population, the patients are well characterised from a clinical perspective and the gene pool has remained relatively homogenous. In addition the number of specialists dealing with MND patients in Ireland is extremely small allowing near 100% capture of the population. Up until recently no data has been available for comparison on the MND population in Northern Ireland (NI) which comes under the jurisdiction of the UK NHS.

The first part of this study aimed to update and reanalyse the Irish MND population data. In particular it was of interest to compare current incidence and prevalence data from a study published in 1999 to examine for changing population trends after introduction of new standards of care in nutritional and respiratory management of MND. In addition we extended advice and support to the NI MND services in the establishment of a sister register in NI such that 'all Ireland' MND population data could be calculated, this is part of an MD thesis by Dr Colette Donaghy in NI. We discovered relatively stable epidemiology in our MND population over the last decade with identical figures produced by the NI MND register. It would appear that new standards of care have not yet impacted life expectancy in the Irish MND population but further study is required in the future.

Age, male gender, family history and smoking are the only known risk factors (RFs) for MND to date. Identifying potential RF for MND may allow avoidance of high risk activities in those with other predisposing factors. Athleticism or a history of heavy physical activity is a controversial putative RF for MND. We conducted a prospective case control study to evaluate this hypothesis using a validated lifetime historical activity questionnaire. We found that a history of exercise did increase the risk of MND, particularly spinal onset disease and that physical activity conducted at work can contribute significantly to calculated figures and should not be omitted. In addition significant differences in energy expenditure defined as 'vigorous' were noted between MND cases and controls.

Deficiency of insulin-like growth factor (IGF) has been described in MND patients. Whether this is coincidental or a primary or secondary phenomenon in the disease is unclear. Many other factors can influence IGF levels such as starvation and stress. We conducted both cross sectional and longitudinal studies of IGF in our MND cases and compared them to populations with multiple sclerosis (MS), post-polio syndrome (PPS) and normal controls. In addition nutritional and functional indices were evaluated serially and correlated with IGF data. Our data confirmed perturbations in the IGF system in MND and suggested that IGF-1 levels dip pre-agonally in MND patients.