P115 IMPLEMENTATION OF A NATIONAL AMYOTROPHIC LATERAL SCLEROSIS REGISTRY
HORTON KD, MURAVOV O, KAYE W, SANCHEZ M
ATSDR/DHS/SRB, Atlanta, GA, United States
E-mail address for correspondence: [email protected]
Keywords: registry, national databases, pilot projects
The uncertainty about the incidence and prevalence of Amyotrophic Lateral Sclerosis (ALS), as well as the lack of knowledge about the role of environmental exposures in the etiology of ALS, have created a need for structured data collection through a national ALS registry. In 2008, President Bush signed a law that provides for a national ALS registry to be created. Prior to this law being enacted, the Agency for Toxic Substances and Disease Registry (ATSDR) was already conducting four pilot projects (during 2006–2009) to determine the feasibility of creating a national ALS registry. Results from the pilot projects concluded that a national ALS registry is feasible; however, several different methodologies would be needed for identifying a large portion of individuals with ALS. Therefore, in 2009, ATSDR began implementation of the National ALS Registry using a two-pronged approach to help identify all US cases of ALS. The first approach, currently being undertaken, utilizes existing national administrative databases to identify prevalent cases, based on an algorithm developed from the pilot projects. Results from the national administrative databases will be presented if available. The second approach, which will be implemented in fall 2010, will use a secure web portal to identify cases missed by the national administrative databases. Also, to improve the completeness of the National ALS Registry, ATSDR is concurrently implementing registries that will allow for timely population-based case estimates of ALS in smaller defined geo graphic areas (ie, at the state and metropolitan levels). The pur pose of this presentation is to provide an overview of the deve lopment and implementation of the National ALS Registry.
P116 MULTI-CENTER, INTERNET-ACCESSIBLE ALS PATIENT CLINICAL OUTCOMES REGISTRY CONTAINING DE-IDENTIFIED CLINICAL DATA DRAWN FROM THREE US CENTERS
BOYLAN K1, BROOKS BR2, GRAVES M3, SEPULVEDA L3
1Mayo Clinic, Jacksonville, Florida, United States, 2Carolinas Medical Center, Charlotte, North Carolina, United States, 3University of California, Los Angeles, California, United States
E-mail address for correspondence: [email protected]
Keywords: outcomes registry, database, software
Background: Patient registries are integral to clarifying the clinical course, prognosis and treatment of ALS. Progress in this area has been limited by lack of standardized software tools that are readily accessible, clinically integrated, searchable, and analytically practical at both the individual patient and aggregate level across multiple centers.
Objectives: Demonstrate feasibility of a standardized, internet-accessible archive of pooled, de-identified clinical data on ALS patients from site specific databases at multiple centers to serve as a basis for multi-center clinical and epidemiological research in ALS.
Methods: Using a commercially available program, the University of California, Los Angeles (UCLA), Carolinas Medical Cen ter and Mayo Clinic Florida (MCF) established a common data set based on core data elements used in the NINDS DNA banking repository (1) to create an independent registry of de-identified clinical data. The 1275 page Data Dictionary was reiteratively tested and modified at three separate sites to provide minimal and expanded data element capability. Each center also customized the database registry based on individualized req uirements at the respective centers, including server hosting.
Results: The ALS database at UCLA functions as an electronic medical record containing medical records, clinical and laboratory data for the ALS clinic, supports generation of prescriptions for equipment and medications, and allows patients and caregivers to enter data online and receive educational materials. The databases at all 3 centers serve as patient registries to support research. The MCF database also supports data collection in ALS clinical trials. The database program allows export of de-identified batch data and uploads into a central, multi-center registry (about a 10 minute process). The multi-center database, maintained on a secure server, is not directly linked to the database at any of the 3 centers.
Conclusion: We demonstrate feasibility of an internet-accessible, multi-center ALS patient registry containing de-identified common data elements uploaded from actively maintained databases at 3 independent ALS centers, driven by off-the-shelf commercially available database software.
Discussion: A common database program with shared field codes facilitates data sharing without compatibility issues or need for data transformation. Data transfer to the multi-center registry is controlled by source data administrators at each site, without risk of external, unauthorized access to the source database. The source databases cannot be accessed by users of the multi-center database. The database program supports lon gitudinal data collection, clinical trial management, and a patient portal for data entry and delivery of educational materials. The Data Dictionary will be made freely available to all ALS Clinic sites that want to enter into a national ALS patient clinical outcomes registry that might be a means to permit Joint Commission Accreditation Program ALS Disease Specific Certification or patient safety registries.
Reference:
- Gwinn K, Corriveau RA, Mitsumoto H, et al. PLoS ONE 2007;2:e1254.
P117 A POPULATION-BASED STATEWIDE REGISTRY OF PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS IN MASSACHUSETTS
KNORR R1, CONDON S1, FISCHETTI C1, ARMON C2
1Massachusetts Department of Public Health, Boston, MA, United States, 2Baystate Medical Center, Springfield, MA, United States
E-mail address for correspondence: [email protected]
Keywords: registry, epidemiology, prevalence
Background: Prior to the development of the Massachusetts ALS Registry, there have been no population-based registries for ALS in the US. Beginning in 2003, following a legislative mandate and the inclusion in state regulations of ALS as a reportable condition possibly linked to environmental exposures, Massachusetts has been developing the tools needed to establish a statewide registry. Following completion of pilot studies and focus groups, registry data collection was initiated on January 1, 2008 for the ascertainment of 2007 prevalent cases.
Objectives: The primary objective of the Registry is to identify all prevalent and incident cases of ALS in Massachusetts in order to better understand trends and patterns of the disease. The secondary objective is to create a patient database to stimulate research into causes and/or treatments of ALS.
Methods: Primary data sources are 650 neurologists in private, clinic, or hospital practice and the medical record department of hospitals. Secondary data sources, such as death certificates, hospice organizations, and patient advocacy groups are used to determine if cases are missed using primary sources. For each patient identified, trained nurses abstract a standardized set of data at each practice and photocopy the source documentation. The diagnosis of ALS is classified according to the revised World Federation of Neurology criteria for the diagnosis of ALS by neurologists experienced in applying these criteria.
Results: The collection of 2007 prevalent cases has been completed and data collection is on-going for subsequent years. The crude statewide prevalence was 4.62/100,000, which includes Definite, Probable, and Lab-supported Probable ALS based on El Escorial criteria. Upon inclusion of Possible ALS, the crude prevalence was 4.97/100,000. Inclusion of Primary Muscular Atrophy and Primary Lateral Sclerosis cases, which make up a portion of the Suspected ALS category, lead to a crude prevalence of 5.96/100,000. The breakdown of eligible cases by El Escorial criteria is as follows: 18.0% definite ALS; 20.4% probable ALS; 13.1% laboratory-supported probable ALS; 4.0% possible ALS; 19.7% suspected ALS. 19.7% of patients did not have ALS according to the El Escorial criteria. The remaining cases were unable to be analyzed due to insufficient information from medical records.
Discussion and conclusions: Results will be analyzed by community in Massachusetts to evaluate trends and patterns throughout the state. As additional years of data are added to the registry, we will have greater statistical power to investigate etiologic hypotheses such as the role the environment may play in ALS. Our data will also be available to other researchers and public health professionals.
P118 THE LJUBLJANA ALS DATABASE: CLINICAL FEATURES OF OUR PATIENTS
KORITNIK B, ZGONC V, LEONARDIS L, DOLENC GL, RISTIC KS, STUKOVNIK V, ZIDAR I, ZIDAR J
Institute of Clinical Neurophysiology, University Medical Centre Ljubljana, Ljubljana, Slovenia
E-mail address for correspondence: [email protected]
Keywords: database, survival, disease progression
Background: Knowledge of clinical and demographic data on ALS patients is important to identify prognostic factors of the disease. This might help health professionals in better treat ment planning and timely introduction of interventions. It can also help patients and their caregivers to better cope with the disease and to schedule their activities during the disease course.
Objectives: The aim of our database is to gather the available clinical and demographic information on the ALS patients seen by the Ljubljana ALS team. We also wanted to use the data to explore the disease course within different subgroups and to look for possible prognostic factors.
Methods: We included all patients with ALS that were referred to be seen by the Ljubljana ALS team between October 2002 and December 2009. The data was gathered at regular patient visits that were scheduled every 3 months. Some of the patient data was collected retrospectively based on patient notes.
Results: 167 (47% men, 53% women) were identified. Mean age at disease onset was 62 years (range 32–82), 63 years in women and 61 years in men. The disease started as spinal form in 66% and as bulbar form in 30%. Four patients (2%) had the familial form of the disease. According to El Escorial diagnostic criteria (EDC) at the time of referral, 29% of patients had definite, 41% probable and 14% possible form of ALS. Walking problems occurred in 88% of patients during the course of the disease. 46% were eventually unable to ambulate independently. 32% percent of patients were unable to feed themselves. 70% had speech problems, 35% became anarthric. Swallowing problems occurred in 72% of patients and in 35% PEG was performed. 64% of patients experienced breathing problems. 23% opted for noninvasive ventilation while only 2% of patients were tracheotomised. The median survival time from symptom onset was 23 months (2–114). The median survival time after diagnosis was 12 months (0–53). In those with PEG, the median survival time after this intervention was 5 months (0–27).
Conclusion: Although not being a population study, by using the database, we were still able to get some interesting insights into the disease course. The database will possibly form the basis for a national ALS registry in Slovenia. This is also a first sur vey of ALS patients in Slovenia and the data can be used for comparison with other similar studies.
P119 MORTALITY DATA AND DEATH CERTIFICATION FOR AMYOTROPHIC LATERAL SCLEROSIS
GEORGOULOPOULOU E, SOLA P, GOLDONI CA, BERNABEI C, NICHELLI P, MANDRIOLI J,
Department of Neuroscience, Nuovo Ospedale Civile S. Agostino-Estense, University of Modena and Reggio Emilia, Modena, Italy
E-mail address for correspondence: [email protected]
Keywords: mortality, epidemiology, death certification
Background: Despite the efforts made to improve the accuracy of death certification for ALS, these data often lack sensitivity and specificity. However, a fairly homogeneous accuracy is reported among different countries: previous studies have found that 72–90% of the cases had ALS listed as the primary cause of mortality on death certification.
Objectives: To evaluate mortality data and the sensitivity and specificity of death certification for ALS in Modena, Italy.
Methods: All the cases deceased during the period 2000–2009 were ascertained through these different sources: 1) the population based registry of ALS in the province of Modena which has been in operation from 2000; 2) the computerized discharge archive of Modena; 3) the death certificates of residents in the province who died from ALS.
Results: From 2000 to 2009 considering all the above-mentioned sources, 142 residents died from ALS; mean age at death was 69 years. Death certificates were available for the totality of the patients. ALS was indicated as the primary cause of death in 119 cases (sensitivity: 83.80%). Mean age at death was 69 years. The number of patients known to have ALS in their lives but not captured by death certificates was 23 (false negatives: 16.20%; mean age at death: 74 years). In these cases cause of death was indicated as pneumonia (22%), heart disease (17%), tumors (14%); stroke, dementia, brain tumor, muscular dystrophy, spine disease were also indicated as primary causes of clinically confirmed ALS cases. In 35% of cases the primary cause was one of the known co-pathologies of the patients. Death occurred at home in the 69% of cases. ALS was listed as a cause of death in 14 cases that were unknown to the registry (11.76%) probably because they were followed in other provinces of Italy. Among these cases, for 9 there were clinical data supporting the diagnosis of ALS and 2 were familial ALS; for 5 cases there was no available record of a diagnosis during life (likely false positive: 4.20%).
Conclusions: These data are quite good if compared with international data on death certificate accuracy, but they underline an evident underreporting of ALS as the primary cause of death. Therefore the use of mortality data based on death certificates as a surrogate of incidence rates is not recommended. Conversely death certification has a low false positive rate and can be useful to integrate clinical data from population based registries, particularly in consideration of the recent introduction of data protection laws.
P120 CHANGES IN THE EPIDEMIOLOGY OF AMYOTROPHIC LATERAL SCLEROSIS IN MODENA, ITALY, FROM 1990 TO 2009
GEORGOULOPOULOU E, SOLA P, BERNABEI C, NICHELLI P, MANDRIOLI J
Department of Neuroscience, Nuovo Ospedale Civile S. Agostino-Estense, University of Modena and Reggio Emilia, Modena, Italy
E-mail address for correspondence: [email protected]
Keywords: epidemiology, incidence, prevalence
Background: Few studies deal with the temporal trend of ALS incidence: a study from Rochester, Minnesota, reported a constant ALS incidence rate of 1.7/100,000. Other non population based studies reported increasing ALS incidence rates through the years, and an increasing ALS mortality over time, especially in the elderly. More than one independent study has shown an increasing ALS prevalence and survival in relation to a multidisciplinary approach, to an increased use of non-invasive ventilation and to an increased attention to nutrition.
Objective: To study the changes in ALS epidemiology from 1990 to 2009 in the province of Modena.
Materials and methods: From 1990 through 2009 cases were ascertained from all the neurological centers and hospitals of the province of Modena, death certificates, and the Italian ALS Association. A population based registry of ALS in the province of Modena has been in operation since 2000.
Results: During the period considered, 326 residents (166 men, 160 women) received a diagnosis of ALS. The average annual ALS incidence was 2.58/100,000, with a constant incidence increase with increasing age (mean age at onset: 64 years). Incidence rate was 2.18/100,000 in the years 1990–99 and 2.94/100,000 in the years 2000–09. Mortality rates were quite stable: 1.88/100,000 in the first decade, to 2.17/100,000 in the second decade. The prevalence rates were 1.83/100,000 in 1990, 4.31/100,000 in 2000, and 11.48/100,000 in 2009. The 50% of patients diagnosed after 2000 survived 40 months, whereas the 50% of patients diagnosed before survived 27 months (P<0.001 logrank test). Survival was worse in bulbar form and older people; also non-invasive ventilation and PEG use were associated to a longer survival.
Discussion: Comparing the present data with the retrospective ones, we observe a marked increase of ALS prevalence, in spite of a mild increase of incidence and mortality. A more accurate case ascertainment, an improved ALS diagnostic process, and a greater attention to the disease can explain these data. The prevalence values in our province are very high, perhaps in relation to long survivors. The increase in survival may be ascribed to improved patients’ care, with a timely treatment of dysphagia, malnutrition, and respiratory failure.
Conclusions: We can conclude that the genuine change in ALS epidemiology over time concerns ALS prevalence and survival. The increase in ALS survival and prevalence, with prevalence rates among the highest previously reported, underlines the importance of palliative care and specialized centers for MND diseases.
P121 A FOLLOW-UP STUDY ON ALS IN THE KOZA/KOZAGAWA/KUSHIMOTO FOCUS AREA OF THE KII PENINSULA FROM THE 1960S TO THE 2000S: A NEW CLUSTER OF ALS
KIHIRA T1, YOSHIDA S1, KONDO T2, OKAMOTO K3, KOKUBO Y4, KUZUHARA S5,4
1Kansai University of Health Sciences, Kumatori, Osaka, Japan, 2Wakayama Medical University, Kimiidera, Wakayama, Japan, 3Aichi Prefectural University, Nagoya, Aichi, Japan, 4Mie University Graduate School of Medicine, Tu, Mie, Japan, 5Suzuka University of Medical Science, Suzuka, Mie, Japan
E-mail address for correspondence: [email protected]
Keywords: Kii-ALS, incidence, calcium
Background: In the 1960s, the incidence of ALS was high in the southern part of the Kii Peninsula, especially in Koza/Kozagawa/Kushimoto area (K area), where the drinking water was supplied from the Kozagawa river and had an extremely low calcium (Ca) content. The incidence of ALS in K area gradually decreased in the 1980s. Recently, however, new patients were found in residents on a small island Oshima close to the K area where no patients had been found between 1965 and 1999. In Oshima, the drinking water previously had contained high Ca until 1975 when the water supply was changed from wells to the Kozagawa river.
Objectives: We investigated the changes in incidence of ALS in K area and Oshima between 1967 and 2008 with special reference to Ca concentrations in drinking water.
Methods: Probable and definite ALS patients, the diagnosis of which was made by neurologists according to the El Escorial criteria in K area and Oshima were collected during three research periods: period I, between 1967 and 1971; period II, between 1989 and 1999; and period III, between 2000 and 2008. The concentrations of Ca and Mg in the drinking water and in the regional river were measured.
Result: The crude incidence of ALS in K area (population, 23,357) was 5.7/100,000 in period III, which was similar to 6.0/100,000 in period I. In Oshima, while no patients were found during periods I and II, the crude incidence was 31.2/100,000 in period III (population, 1,069). The age- and sex-adjusted incidence (in 2000 census) of K area was 2.3/100,000; that of Oshima, 9.0/100,000 and that of Kozagawa, 4.5/100,000 (pop ulation, 3,426), in period III. The drinking water of Oshima and Kozagawa contained low Ca (3.0 ppm) similar to that of K area.
Discussion: The recent high crude incidence of ALS in K area might be partly attributable to an increase in the senility rate in the population. In contrast, the age- and sex-adjusted incidence of ALS was high in Oshima and Kozagawa, between 2000 and 2008, although continuous study over a longer period is necessary because of the small population. It is noteworthy that no patient with ALS was found in Oshima for 35 years, in contrast to the K area. The recent low Ca concentration in the drinking water in Oshima might have some role in the appearance of a new high incidence district in the Kii Peninsula.
Conclusions: We have demonstrated that the recent incidence of ALS was high in Kozagawa and Oshima, and that the drinking water of these districts contained low Ca. The relationship between high incidence of ALS and low Ca concentration in the drinking water should be pursued in future.
P122 GENDER DIFFERENCES IN THE RELATIONSHIP BETWEEN LIFESTYLE FACTORS AND RISK OF AMYOTROPHIC LATERAL SCLEROSIS
OKAMOTO K1, KIHIRA T2, KOKUBO Y3, NAGAI M4
1Aichi Prefectural University School of Nursing, Nagoya, Japan, 2Kansai University of Health insulance, Osaka, Japan, 3Mie University School of Medicine, Mie, Japan, 4Saitama Medical College School of Medicine, Saitama, Japan
E-mail address for correspondence: [email protected]
Keywords: gender, lifestyle factors, epidemiology
Objective: Few human studies have reported sex differences in the relationship between lifestyle factors and the risk of amyotrophic lateral sclerosis (ALS). We therefore analyzed gender differences in the relationship between lifestyle factors and the risk of ALS using a case-control study in Japan.
Methods: The study comprised 183 ALS patients diagnosed by EI Escorial World Federation of Neurology criteria, and 407 gender- and age- matched controls randomly selected from the general population. A structured self-administered questionnaire specifically designed for this case-control study was distributed and collected by mail in both patients and controls. We asked patients to recall their lifestyle within the 3 years before the onset of ALS, and controls within the 3 years before the survey. The strength of association between ALS and a potential risk factor was assessed by calculating odds ratios (ORs) and 95% confidence intervals (CIs).
Results: An increased risk of ALS was significantly associated with type A behavior pattern and a less frequent intake of green vegetables in both men and women. In males only, vigorous physical activity and much self reported stress were associated with an increased risk of ALS. The greatest effect on risk for ALS was posed by the combination of a type A behavior pattern and a less frequent intake of green-yellow vegetables, for either each gender or both. We observed a sig-nificant increased risk of ALS for women who had a less frequent intake of green vegetables without a type A behavior pattern.
Conclusion: Type A behavior pattern and a less frequent intake of green vegetables were independently associated with an increased risk of ALS for each gender, and marked gender-differences in the relationship of type A behavior pattern alone or a less frequent intake of green vegetables alone to the risk of ALS were observed. This suggests that gender-specific primary prevention of ALS based on gender-differences in imbalances between the excessive production of oxidants originating from patient-specific factors and the decrease in or lack of an anti oxidant system in motor neurons may be more important.
P123 LIFETIME ESTROGEN EXPOSURE AND THE RISK OF AMYOTROPHIC LATERAL SCLEROSIS
DE JONG S1, VELDINK JH1, HUISMAN M1, SUTEDJA N1, VAN DER KOOI A2, DE VISSER M2, SCHELHAAS J3, VAN DEN BERG LH1
1Department of Neurology, Rudolf Magnus Institute of Neuroscience University Medical Center Utrecht, Utrecht, Netherlands, 2Department of Neurology, Academic Medical Center, Amsterdam, Netherlands, 3Department of Neurology, Radboud University Medical Center, Nijmegen, Netherlands
E-mail address for correspondence: [email protected]
Keywords: estrogens, risk, population-based
Background: The pathogenesis of amyotrophic lateral sclerosis is considered to be multifactorial. Several epidemiological studies showed a lower incidence of ALS in women than in men, most distinctively before menopausal age. These results suggest a possible protective effect of female reproductive hormones, especially endogenous estrogens.
Objectives: The aim of this study was to establish the relationship between endogenous estrogen exposure and ALS in a large and representative, prospectively collected patient group compared to population-based controls.
Methods: We performed a population-based case-control study in the Netherlands. Patients were diagnosed according to the established El Escorial criteria. Multivariate logistic regression analysis was performed in patients diagnosed with ALS after January 1st, 2006. Population-based controls were mainly recruited through the general practitioner of the patient. Patients and controls were sent a questionnaire. Data on reproductive history were collected. Only women with a natural menopause were included.
Results: Data from 131 incident patients and 430 controls were analysed. Multivariate analyses showed an increased risk of ALS in women with a higher age at menarche (OR 1.16 (95% CI 1.01–1.33)) and a shorter menarche-menopause interval (OR 0.95 (95% CI 0.91–0.99)). Also a lower body mass index before disease onset was associated with an increased risk of ALS (OR 0.92 (CI 95% 0.87–0.98)). A lower lifetime exposure to estrogens is associated with a worse prognosis (HR 0.93 (95% CI 0.88–0.98).
Discussion: This study provides evidence that a lower level of endogenous estrogen exposure and a lower body mass index are independently associated with an increased risk of ALS. Also, a lower level of endogenous estrogen exposure is associated with a worse prognosis.
Conclusion: This study provides evidence that a lower level of endogenous estrogen exposure and a lower body mass index are independently associated with an increased risk of ALS. Also, a lower level of endogenous estrogen exposure is associated with a worse prognosis.
P124 INFLUENCE OF PHYSICAL ACTIVITY IN THE EVOLUTION OF ALS
RODRIGUEZ DE RIVERA FJ, SANZ GALLEGO I, OREJA GC, DIEZ TE
ALS Unit, Hospital Universitario La Paz, Madrid, Spain
E-mail address for correspondence: [email protected]
Keywords: physical activity, evolution
Background: Previous studies tried to find a causal relationship between intense physical activity and the development of ALS without success. Nevertheless it has not been studied if these patients were evolving differently than the rest of the ALS patients.
Objectives: Our aim is to evaluate if there are differences in the evolution of patients with an intense physical activity during the first 2 years after the diagnosis.
Methods: A descriptive study of consecutive patients attended from the moment of diagnosis with quarterly reviews in the ALS Unit from 2006 to 2010 was done. The age of onset, the initial localization of the symptoms, the worsening of the functional state (scale ALSFRS-r), the respiratory function, the appearance of dysphagia and signs of depression and/or signs of Frontotemporal dementia were evaluated in relation to intense physical activity.
Results: Forty two patients (30 M and 12 W) were evaluated with an average age of onset of 57.97 years old. Eleven of these patients (10 M and 1 W with an average of age of onset of 47.45 years old) had precedents of an intense physical activity (7 sportsmen, 2 military men, 2 others) (Patients with Physical Activity (PPhA vs NoPhA)). The initial form was spinal in 81.81% and bulbar in 18.18% (NoPhPA S 61.29%; B 38.7%). The worsening of the functional state (PPhA 45.27 points ALSFRS-r at the beginning to 22.88 at 24 months (−22.39 pts) vs NoPhA 41.58 to 17.17 (−24.41pts)), the need of Non-Invasive Ventilation (44.44% vs 53.57%), the presence of dysphagia (33.33% vs 70.96%), signs of depression (36.36% vs 70.96%) and signs of frontotemporal dementia (27.27% vs 35.48%) were significantly less at 24 months of evolution in the PPhA patients. There were no statistically significant differences in the mortality.
Conclusions: Patients with intense physical activity are young males and their initial symptoms were predominantly spinal. PPhA patients have a slow clinical deterioration compared to other ALS patients during 24 months after diagnosis, though there are no significant differences in the mortality.
P125 SMOKING, ALCOHOL AND THE RISK OF AMYOTROPHIC LATERAL SCLEROSIS: A POPULATION-BASED STUDY
DE JONG S1, VELDINK JH1, HUISMAN M1, SUTEDJA N1, VAN DER KOOI A2, DE VISSER M2, SCHELHAAS J3, VAN DEN BERG LH1
1Department of Neurology, Rudolf Magnus Institute of Neuroscience University Medical Center Utrecht, Utrecht, Netherlands, 2Department of Neurology, Academic Medical Center, Amsterdam, Netherlands, 3Department of Neurology, Radboud University Medical Center, Nijmegen, Netherlands
E-mail address for correspondence: [email protected]
Keywords: smoking, alcohol, population-based
Background: The pathogenesis of amyotrophic lateral sclerosis (ALS) is considered to be multifactorial and smoking has previously been posed as a possible risk factor in ALS. The level of education and alcohol consumption are assumed to be associated with cigarette use, and are therefore potential confounders. Previous studies yielded conflicting results due to methodological limitations and large population-based studies could strengthen the evidence.
Objective: The aim of this study was to establish the relationship between smoking and ALS in a large and representative, prospectively collected patient group compared to population-based controls.
Methods: We performed a population-based case-control study in the Netherlands. Patients were diagnosed according to the established El Escorial criteria. Multivariate logistic regression analysis was performed in patients diagnosed with ALS after January 1st, 2006. Population-based controls were mainly recruited through the general practitioner of the patient. Patients and controls were sent a questionnaire. Data on lifetime history of smoking, level of education and alcohol consumption were collected.
Results: Data from 494 incident patients and 1599 controls were analysed. Multivariate analyses showed an increased risk of ALS in current smokers (OR 1.38 (95% CI 1.02–1.88)) and those with a lower level of education (OR 1.94 (95% CI 1.31–3.08)) and a reduced risk of ALS in those with current alcohol consumption (OR 0.52 (95% CI 0.40–0.75)). Also, current smoking had a significant effect on survival with a hazard ratio (HR) of 1.51 (95% CI 1.07–2.15), adjusted for vital capacity, gender, age and site of onset and had a notably larger effect on survival in women (HR 2.12 (95% CI 1.25–3.61)). There was no interaction between smoking and alcohol use.
Discussion: We conclude this study provides evidence that cigarette smoking and a lower level of education are independently associated with an increased risk of ALS and alcohol consumption independently with a reduced risk of ALS. Also, current smoking is associated with a worse prognosis, especially in women and independently from forced vital capacity. Furthermore, this study shows that a suspected risk factor for ALS should be studied in an incident population-based patient group, when an effect on survival is also present.
Conclusion: Cigarette smoking and a lower level of education are associated with an increased risk of ALS and alcohol consumption with a reduced risk of ALS.
P126 ANALYSIS OF CO-MORBID CONDITIONS IN STUDIES OF AMYOTROPHIC LATERAL SCLEROSIS
WALLACE K, LANKA V, SHERMAN A, CUDKOWICZ M
Massachusetts General Hospital, Charlestown, MA, United States
E-mail address for correspondence: [email protected]
Keywords: co-morbid conditions, prevalence, clinical trials
Background: Most studies on Amyotrophic Lateral Sclerosis (ALS) collect data regarding non-ALS medical conditions. Such data may elucidate the more common co-morbidities within an ALS subject population. Additionally, it may provide a ‘timeline’ that chronicles another condition's diagnosis relative to the subject's ALS diagnosis.
Objective: The purpose of this analysis is to better understand which co-morbidities exist within the ALS-diagnosed populations. Within this objective, we sought to: 1) determine which ‘medical body systems’ categories had the highest concentration of co-morbidities, 2) derive which disorders are more prevalent and still exist post-ALS diagnosis, and 3) perform a sub-analysis where temporality of co-morbidity diagnosis is known with respect to the ALS diagnosis.
Methods: Data were pooled from eleven studies conducted at Northeast ALS Consortium's sites. Subject data were included if there was a substantiated date of ALS diagnosis that could be linked to data in co-morbidities case report forms that provide the data elements of a ‘Body System’ category, description of a condition and whether the condition was present at screening. ‘Year of Diagnosis’ data element was required for the subject to be included in the sub-analysis. For the co-morbidity ‘free-text’ comparisons, standardized coding terminology from MedDRA and DSM-IV were used in coding algorithms. Microsoft Excel and SAS v9.1 were used for calculations.
Results: The overall analysis revealed that the most prevalent medical body system categories were ‘Musculoskeletal’, ‘HEENT’ and ‘Autoimmune Disorders’. When examining only those co-morbid conditions that were present at screening, these included ‘Mood Disorders’, ‘Hypertension’ and ‘Allergies’. In the sub-analysis, ‘Musculoskeletal’ was also the most prevalent pre-ALS diagnosis medical body system category, followed by ‘Genitourinar y’ and ‘Cardiovascular’. The most prevalent pre-ALS diagnosis co-morbid conditions were ‘Fractures’, ‘Major OBGyn with general anesthesia’ and ‘Cancer’. The most prevalent co-morbid conditions at screening were ‘Mood Disorders’, ‘Sleep Disorders’ and ‘Generalized Body Pain’.
Conclusion: 1) A lot could be gained from analyses of co-morbid conditions, both prior to ALS diagnosis and post-diagnosis; 2) Recommendations could be developed for targeted interventions for subjects regarding co-morbidities; 3) Certain data collection improvements are desirable: Utilize standard data elements to collect co-morbidities across future ALS studies; Use medical data dictionaries (MedDRA, etc.) to code ‘Medical Body Systems’ categories; Introduce standard approach for analyzing ‘free-text’ format for co-morbid conditions.
P127 RE-WRITING HISTORY: LOCKHART CLARKE'S FORGOTTEN DESCRIPTIONS OF ALS FROM THE 1860S
TURNER M1, SWASH M2, EBERS G1
1Oxford University, Oxford, United Kingdom, 2University of London, London, United Kingdom
E-mail address for correspondence: [email protected]
Keywords: history, neuropathology, pioneers
Background: It is accepted that others, including Charles Bell, François-Amilcar Aran and Jean Cruveilhier, had recognised a progressive lower motor neuron-only syndrome from at least the 1830s, before Jean-Martin Charcot's first use of the term ALS in 1874 (nine years after his first case report). Although the definitive term ALS, that acknowledged both upper and lower motor neuron involvement, is attributed to Charcot, William Gowers first grouped the three phenotypes of amyotrophic lateral sclerosis, progressive muscular atrophy and progressive bulbar palsy together as part of the same syndrome. The term MND as an over-arching label was not suggested until nearly a century later by W. Russell Brain.
The forgotten cases: Augustus Jacob Lockhart Clarke (1817–1880), a physician on the staff of the Hospital for the Paralysed and Epileptic in Regent's Park London, is best known for his descriptions of spinal cord anatomy. However two published and detailed case reports from the 1860s (pre-Charcot) have emerged in which he also carried out rigorous post-mortem neuropathological studies of what appear to be classical cases of ALS (1, 2). He clearly recognised the additional involvement of the corticospinal tracts that distinguished this from PMA, captured in beautiful drawings, and indeed his contribution was later acknowledged by Charcot. As well as the painstaking pathological examination, exquisite clinical histories are documented in both cases, the first co-authored with Charles Bland Radcliffe, the other with John Hughlings Jackson. They resonate with contemporary debates concerning the evolution of disease in ALS. Both concern young-onset cases, the first with a military background and the onset attributed to sunstroke, the second apparently post-traumatic (and which later involved a successful pregnancy). The descriptions are graphic and specifically recognise features such as oculomotor, sphincter, sensory and cognitive sparing. Mercury and electrical stimulation were tried therapeutically, along with a diet of ‘eggs, beef-tea, an extra allowance of bread, and half-a-pint of port wine…’ to no avail.
Conclusions: The definition of the clinicopathological entity of ALS evolved over half a century, and Lockhart Clarke must take his rightful place among the other pioneers. His Lancet obituary stated: ‘He was a man single of purpose, of noble independence and honesty, wholly free from ambition…he will be remembered, not as the popular physician, but on account of his patient and laborious researches so fruitful to medical science.’
References:
- Radcliffe CB, Lockhart Clarke J. The British and Foreign Medico-Chirurgical Review. 1862;30.
- Lockhart Clarke J, Hughlings Jackson J. Med Chir Trans 1867;50:489–98.