Irish Amyotrophic Lateral Sclerosis Register Research Articles

Irish Amyotrophic Lateral Sclerosis Incidence: Age, Period, and Cohort Effects Using a Partial Least Squares Regression Model.

To investigate the underlying reasons for variability in the incidence rate of amyotrophic lateral sclerosis (ALS) within the Irish population between the years 1996 and 2021. The Irish ALS register was used to calculate the incidence and to subsequently extract age at diagnosis (age), year of diagnosis (period), and date of birth (cohort) for all incident patients within the study period (n = 2,771). An age-period-cohort (APC) model using partial least squares regression was constructed to examine each component separately and their respective contribution to the incidence while minimizing the well-known identifiability problem of APC effects. A dummy regression model consisting of 5 periods, 19 cohorts, and 16 age groups was used to examine nonlinear relationships within the data over time. The CIs for each of these were estimated using the jackknife method. The nonlinear model achieved R2 of 99.43% with 2-component extraction. Age variation was evident with those in the ages 65-79 years contributing significantly to the incidence (βmax = 0.0746, SE = 0.000410, CI 0.00665-0.00826). However, those aged 25-60 years contributed significantly less (βmin = -0.00393, SE = 0.000291, CI -0.00454 to -0.00340). Each successive period showed an increase in the regression model coefficient suggesting an increasing incidence over time, independent of the other factors examined-an increase of β from -0.00489 (SE = 0.000264, CI -0.00541 to -0.00437) to 0.00973 (SE = 0.000418, CI 0.0105-0.00891). A cohort effect was demonstrated showing that the contribution of those born between 1927 and 1951 contributed to a significantly greater degree than the other birth cohorts (βmax = 0.00577, SE = 0.000432, CI 0.00493-0.00662). Using the Irish population-based ALS Register, robust age, period, and cohort effects can be identified. The age effect may be accounted for by demographic shifts within the population. Changes in disease categorization, competing risks of death, and improved surveillance may account for period effects. The cohort effect may reflect lifestyle and environmental factors associated with the challenging economic circumstances in Ireland between 1927 and 1951. Age-period-cohort studies can help to account for changes in disease incidence and prevalence, providing additional insights into likely demographic and environmental factors that influence population-based disease risk.

What does the ALSFRS-R really measure? A longitudinal and survival analysis of functional dimension subscores in amyotrophic lateral sclerosis

IntroductionALS functional rating scale (revised) (ALSFRS-R) is the most widely used functional rating system in patients with amyotrophic lateral sclerosis (ALS). However, heterogeneity in ALSFRS-R progression renders analysis challenging. We...

Survival analysis of geospatial factors in the Irish ALS cohort

Variations in environmental risk factors potentially influence incidence and progression in complex multifactorial diseases. Few studies have examined the association of survival in amyotrophic lateral sclerosis (ALS) with environmental geospatial variables. Here we use data from the Irish ALS cohort to perform such an analysis. Geographic data sources were used to generate small area values for four geospatial variables (population density, social deprivation, distance to coast, and distance to ALS multidisciplinary (MDT) clinic) for each ALS case on the Irish ALS register. These were combined with follow-up data and used as covariates in Royston-Parmar regression survival analysis including age of onset, site of onset, diagnostic delay, riluzole prescription and MDT clinic attendance as covariates. One thousand, two hundred and thirty-two patients with median survival of 2.31 years from disease onset were included. After addition of the individual geospatial variables in turn, none of the four variables was found to be associated with survival with a p-value <0.05. The results may reflect the public healthcare system that provides riluzole prescription and access to the MDT to all patients free of charge, and is also congruent with our recent finding that social deprivation is not associated with ALS incidence in Ireland.

Spatial cluster analysis of population amyotrophic lateral sclerosis risk in Ireland.

Few spatial cluster analyses of amyotrophic lateral sclerosis (ALS) incidence have been conducted on prospective incident population-based cohorts; we report results of a formal cluster analysis of the Irish ALS cohort from January 1, 1995, to December 31, 2013. We identified 1,684 incident cases from the Irish ALS register. Population data from 4 census years were used to calculate age- and sex-standardized expected ALS cases for 3,355 areas. Spatial cluster analysis was performed to identify high-risk clusters using both SaTScan and FleXScan software. Poisson-based, time period-stratified statistics and time-stratified Bayesian smoothed risk mapping were used to audit completeness of case ascertainment of the register. No significant high-risk clusters of incident ALS were identified. However, SaTScan revealed 2 significant areas of lower-than-average ALS risk-one centered on County Kilkenny (relative risk 0.53, p = 0.012) and a smaller area in County Clare (relative risk 0.0, p = 0.029). Audit of case ascertainment did not indicate any failure to detect cases in these areas. The absence of high-risk ALS clusters in Ireland contrasts with previous studies. Our study has several advantages, notably the use of a long-running prospective ALS register with nationwide case ascertainment. The presence of 2 low-risk areas was unexpected. No obvious ascertainment, demographic, or common environmental factors explain this finding. However, we postulate that historical factors may have led to altered genetic admixture in these regions, possibly contributing to lower rates.

Epidemiology and clinical features of amyotrophic lateral sclerosis in Ireland between 1995 and 2004

Background:We conducted a prospective, population based study to examine trends in incidence and prevalence of amyotrophic lateral sclerosis (ALS) in Ireland from 1995 to 2004.Methods:The Irish ALS Register was used...

Effect of a multidisciplinary amyotrophic lateral sclerosis (ALS) clinic on ALS survival: a population based study, 1996–2000

Background: In recent years, there has been a paradigm shift in the method of healthcare delivery to amyotrophic lateral sclerosis (ALS) patients with the emergence of multidisciplinary ALS clinics that...

An outcome study of riluzole in amyotrophic lateral sclerosis--a population-based study in Ireland, 1996-2000.

Riluzole is the only therapy proven in clinical trials to prolong amyotrophic lateral sclerosis (ALS) survival (approximately three months). Questions remain concerning riluzole's effectiveness in everyday practice, the appropriate duration of treatment, which certain subtypes of ALS specifically benefit from the medication, and whether early administration prolongs survival in ALS patients. We report the results of a population-based outcome study of riluzole in the Irish ALS population over a five-year period. Using data from the Irish ALS Register, we examined the survival of patients diagnosed with ALS between 1 January 1996 and 31 December 2000 who attended a general neurology clinic (n = 264 patients, MD = 16). An intention to treat analysis is employed. 149 (61 %) patients were prescribed riluzole and the remaining 99 (39 %) were not. Riluzole therapy reduced mortality rate by 23 % and 15 % at 6 and 12 months respectively and prolonged survival by approximately four months. This beneficial effect was lost in prolonged follow-up. Suspected or possible ALS patients receiving riluzole experienced similar improvement in survival as the overall cohort. Survival benefit was more marked among patients with bulbar-onset disease. Multivariate analysis did not show riluzole to be an independent predictor of survival. We conclude that riluzole therapy improves ALS survival in everyday clinical practice by a short period of time. This beneficial effect is transient and stopping the medication in advanced ALS should be reconsidered. Bulbar-onset patients appear to particularly benefit from riluzole for unclear reasons. Our initial observations support riluzole use in early ALS.

Clinical features of amyotrophic lateral sclerosis according to the El Escorial and Airlie House diagnostic criteria: A population-based study.

The El Escorial and the revised Airlie House diagnostic criteria for amyotrophic lateral sclerosis (ALS) classify patients into categories reflecting different levels of diagnostic certainty. We conducted a prospective, population-based study of the natural course of ALS in the Republic of Ireland during a 6-year period to examine the utility of these ALS diagnostic criteria. Using data from the Irish ALS Register, we studied the clinical features of all patients diagnosed as having ALS in Ireland throughout their illness. Between 1993 and 1998, 388 patients were diagnosed as having ALS. Forty percent of patients reported bulbar-onset symptoms. Disease progression occurred over time: at last follow-up, 75% of all patients had bulbar signs, compared with 59% at diagnosis. When the El Escorial criteria were applied, more than half of patients (218 [56%]) had definite or probable ALS at diagnosis. Of the 165 possible and suspected ALS cases at diagnosis (trial ineligible), 110 (67%) were trial eligible at last follow-up. Of the 254 patients who had died, 229 (90%) had definite or probable ALS, whereas 25 patients (10%) remained trial ineligible at death. El Escorial category at diagnosis was not a significant prognostic indicator. Use of the Airlie House criteria had no effect on the median time from symptom onset to trial eligibility (12.9 vs 12.8 months). The El Escorial and Airlie House diagnostic criteria are excessively restrictive. Furthermore, levels of diagnostic certainty cannot be used as prognostic indicators. Arch Neurol. 2000;57:1171-1176

Amyotrophic lateral sclerosis mimic syndromes: a population-based study.

The Irish ALS Register is a population-based register of the epidemiological characteristics of amyotrophic lateral sclerosis (ALS) in the republic of Ireland. To describe the clinical and demographic details of those patients included in the Irish ALS Register who were incorrectly diagnosed as having ALS (patients who were ultimately rediagnosed as having an "ALS mimic syndrome"). The medical records of each patient referred to the register are routinely reviewed and, where possible, patients are examined by our group during their illness. Between January 1, 1993, and December 31, 1997, 32 patients (representing 7.3% of 437 referrals) were rediagnosed as having a condition other than ALS. The median age at onset for these 32 patients was 56.0 years (range, 19.5-85.8 years) for men and 53.5 years (range, 39.5-70.4 years) for women. Twenty-nine patients (91%) presented with symptoms referable to the limbs, and the remainder presented with symptoms involving the bulbar musculature. Multifocal motor neuropathy was the most common condition mistaken for ALS, accounting for 7 cases (22%), followed closely by Kennedy disease (4 cases [13%]). Factors leading to diagnostic revision included evolution of atypical symptoms, results of specific investigations, and failure of symptoms to progress. Twenty-seven (84%) of the patients with an ALS mimic syndrome fulfilled the El Escorial criteria for either "suspected" or "possible" ALS, 4 (13%) met the criteria for probable ALS, and 1 (3%) had definite ALS. The application of the El Escorial diagnostic criteria may facilitate early recognition of non-ALS cases. Misdiagnosis of ALS remains a common clinical problem despite the increased availability of investigations and a greater awareness among neurologists of potential diagnostic pitfalls.