National Amyotrophic Lateral Sclerosis Registry Research Articles

History of vigorous leisure-time physical activity and early onset amyotrophic lateral sclerosis (ALS), data from the national ALS registry: 2010–2018

Background: Previous research has suggested that vigorous physical activity (VPA) during adolescence and early adulthood is associated with ALS. The National ALS Registry (Registry) collects physical activity data from persons with ALS. Objective: To examine the association between vigorous VPA and early onset ALS, defined as a diagnosis before age 60, among patients enrolled in the Registry. VPA was defined as engaging in dynamic exercise for at least 10 minutes in a session that caused heavy sweating or large increases in breathing or heart rate. Methods: A cross-sectional study was conducted of 5463 ALS patients with VPA history and 956 ALS patients who never engaged in VPA. Patient characteristics were collected via online surveys in the following areas: demographic, lifetime VPA history, and initial onset of symptoms. General linear modeling was used to estimate mean age of diagnosis and to compute 95% confidence intervals. Results: Patients who reported engaging in VPA at least moderately (three times a week) during early adulthood were more likely to have an ALS diagnosis earlier compared to patients who did not (p < 0.0001). After controlling for year of birth, statistically significant associations between those reporting VPA at age 15–24 and 25–34 and diagnosis of ALS earlier (p = 0.0009, p = 0.0144 respectively). Conclusion: Patients with ALS who had a history of VPA before age 35, were significantly more likely to be diagnosed with ALS before age 60 compared to patients with ALS who never engaged vigorously. More research is needed in the relationship between VPA and early onset ALS.

Physical Activity and early onset amyotrophic lateral sclerosis (ALS), Data from the National ALS Registry: 2010 – 2018 (777)

Physical Activity and early onset amyotrophic lateral sclerosis (ALS), Data from the National ALS Registry: 2010 – 2018 (777)

Gender, reproductive history, and early onset amyotrophic lateral sclerosis (ALS), Data from the National ALS Registry: 2010 – 2018 (1138)

Gender, reproductive history, and early onset amyotrophic lateral sclerosis (ALS), Data from the National ALS Registry: 2010 – 2018 (1138)

Clinical characteristics of a large cohort of US participants enrolled in the National Amyotrophic Lateral Sclerosis (ALS) Registry, 2010–2015

Background: Amyotrophic lateral sclerosis (ALS) is a progressive fatal disease with a varying range of clinical characteristics. Objective: To describe the clinical characteristics in a large cohort of ALS participants enrolled in the National ALS Registry. Methods: Data from ALS participants who completed the Registry’s online clinical survey module during 2010–2015 were analyzed to determine characteristics, such as site of onset, associated symptoms, time of symptom onset to diagnosis, time of diagnosis to hospice referral, and pharmacological and non-pharmacological interventions. Results: Of the 1758 participants who completed the survey, 60.9% were male, 62.1% were 50–69 years old, and 95.5% white. Approximately, 72.0% reported initial limb weakness onset of disease, followed by bulbar (22.1%), and trunk/global onset (6.1%). Other symptoms ever experienced included cramps (56.7%), fasciculations (56.3%), and dysarthria (33.0%). The median time between an increase of muscle cramps until an ALS diagnosis was 12 months; limb onset participants had cramps longer preceding diagnosis versus those with bulbar onset. The most frequent interventions used included riluzole (48.3% currently using), wheelchairs/scooters (32.8%), and noninvasive breathing equipment (30.0%). Participants with trunk/global onset were referred to hospice almost four times earlier than others. Conclusions: These data show how ALS clinical characteristics differ widely in a large cohort of participants preceding diagnosis and reflect variations in disease onset, progression, and prognosis. Better characterization of symptom onset may assist clinicians in diagnosing ALS sooner, which could lead to earlier therapeutic interventions.

Prevalence of Amyotrophic Lateral Sclerosis - United States, 2015.

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a progressive and fatal neuromuscular disease; the majority of ALS patients die within 2-5 years of receiving a diagnosis (1). Familial ALS, a hereditary form of the disease, accounts for 5%-10% of cases, whereas the remaining cases have no clearly defined etiology (1). ALS affects persons of all races and ethnicities; however, whites, males, non-Hispanics, persons aged ≥60 years, and those with a family history of ALS are more likely to develop the disease (2). No cure for ALS has yet been identified, and the lack of proven and effective therapeutic interventions is an ongoing challenge. Treatments currently available, Edaravone and Riluzole, do not cure ALS, but slow disease progression in certain patients (3,4). This report presents National ALS Registry findings regarding ALS prevalence in the United States for the period January 1-December 31, 2015. In 2015, the estimated prevalence of ALS cases was 5.2 per 100,000 population with a total of 16,583 cases identified. Overall, these findings are similar to the 2014 ALS prevalence and case count (5.0 per 100,000; 15,927 cases) (2). Prevalence rates by patient characteristics (most common in whites, males, and persons aged ≥60 years) and U.S. Census regions are consistent with ALS demographics and have not changed from 2014 to 2015 calendar years. The algorithm used to identify cases from national administrative databases was updated from the International Classification of Diseases, Ninth Revision (ICD-9) to the ICD-10 codes for claims starting on October 1, 2015, with no apparent effect on case ascertainment. Data collected by the National ALS Registry are being used to better describe the epidemiology of ALS in the United States and to facilitate research on the genetics, potential biomarkers, environmental pollutants, and etiology for ALS.

Increasing Patient Self-Enrollment in the National Amyotrophic Lateral Sclerosis Registry: Lessons Learned From a Direct to Provider Campaign.

Objective:To conduct educational and promotional outreach activities to general neurologists and to increase self-enrollment of persons with amyotrophic lateral sclerosis (ALS) in the National ALS Registry (Registry).Methods:A multicomponent project to educate neurologists and increase Registry self-enrollment was delivered. Project components consisted of phone calls, mailings, train-the-trainer presentations, and key informant interviews. Project-specific metrics, continuing education enrollment, and Registry self-enrollment data were analyzed to measure project efficacy.Results:Mailings were sent to 1561 neurologists in 6 states during 2015 to 2016. Sixty-five percent of responding neurologists remembered the mailing 3 months after receipt. Of providers who saw patients with ALS in the 3-month period, 60% read the provider guide, 22% distributed a patient guide, and 15% advised a patient to self-enroll. No changes in self-enrollment rates were observed.Conclusion:Targeted mailings to providers can be used to educate them about the Registry; however, most providers did not distribute materials to patients with ALS. Increases in providers receiving Registry material did not lead to increases in patient self-enrollment.Practice Implications:General neurologists have competing priorities, and they see patients with ALS infrequently. Neurologists could be the appropriate channel to distribute Registry information to patients, but they are not the appropriate resource to assist patients with self-enrollment. Engaging the support staff of busy specialists can help increase research response rates and information distribution. The lessons learned from this project can be applied to other rare conditions and disease specialists.

Estimation of the Prevalence of Amyotrophic Lateral Sclerosis in the United States Using National Administrative Healthcare Data from 2002 to 2004 and Capture-Recapture Methodology

Background: National administrative healthcare data may be used as a case-finding method for prevalence studies of chronic disease in the United States, but the completeness of ascertainment likely varies depending on the disease under study. Methods: We used 3 case-finding sources (Medicare, Medicaid, and Veterans Administration data) to estimate the prevalence of amyotrophic lateral sclerosis (ALS) in the United States for 2002–2004, and applied the capture-recapture methodology to estimate the degree of under-ascertainment when relying solely on these sources for case identification. Results: Case-finding completeness was 76% overall and did not vary by race, but was lower for males (77%) than for females (88%), and lower for patients under age 65 (66%) than patients over age 65 (79%). The uncorrected ALS prevalence ratio was 2.8/100,000 in 2002, 3.3/100,000 in 2003, and 3.7/100,000 in 2004. After correcting for under-ascertainment, the annual prevalence increased by approximately 1 per 100,000 to 3.7/100,000 in 2002 (95% CI 3.66–3.80), 4.4/100,000 in 2003 (95% CI 4.34–4.50), and 4.8/100,000 in 2004 (95% CI 4.76–4.91). Conclusions: Federal healthcare claims databases ascertained are a very efficient method for identifying the majority of ALS-prevalent cases in the National ALS Registry, and may be enhanced by having patients self-register through the registry web portal.

“ALS reversals”: demographics, disease characteristics, treatments, and co-morbidities

Objective: To identify differences in demographics, disease characteristics, treatments, and co-morbidities between patients with “amyotrophic lateral sclerosis (ALS) reversals” and those with typically progressive ALS. Methods: Cases of possible ALS reversals were found in prior publications, in the Duke ALS clinic, through self-referral or referral from other Neurologists, and on the internet. Of 89 possible reversals identified, 36 cases were included because chart or literature review confirmed their diagnosis and a robust, sustained improvement in at least one objective measure. Controls were participants in the Pooled Resource Open-Access ALS Clinical Trials database and the National ALS Registry. Cases and controls were compared using descriptive statistics. Results: ALS reversals were more likely to be male, have limb onset disease, and initially progress faster. The prevalences of myasthenia gravis (MG) and purely lower motor neuron disease in cases were higher than estimates of these prevalences in the general population. The odds of taking curcumin, luteolin, cannabidiol, azathioprine, copper, glutathione, vitamin D, and fish oil were greater for cases than controls. Conclusions: When compared to patients with typically progressive ALS, patients with reversals differed in their demographics, disease characteristics, and treatments. While some of these patients may have had a rare antibody-mediated ALS mimicker, such as atypical myasthenia gravis, details of their exams, EMGs and family histories argue that this was unlikely. Instead, our data suggest that ALS reversals warrant evaluation for mechanisms of disease resistance and that treatments associated with multiple ALS reversals deserve further study.

Prevalence of Amyotrophic Lateral Sclerosis - United States, 2014.

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a progressive and fatal neuromuscular disease; the majority of ALS patients die within 2-5 years of receiving a diagnosis (1). Familial ALS, a hereditary form of the disease, accounts for 5%-10% of cases, whereas the remaining sporadic cases have no clearly defined etiology (1). ALS affects persons of all races and ethnicities; however, whites, males, non-Hispanics, persons aged >60 years, and those with a family history of ALS are more likely to develop the disease (1-3). No cure for ALS has yet been identified, and the lack of proven and effective therapeutic interventions is an ongoing challenge. Current treatments available do not cure ALS but have been shown to slow disease progression. Until recently, only one drug (riluzole) was approved to treat ALS; however, in 2017, the Food and Drug Administration approved a second drug, edaravone (4).

A spatial analysis of amyotrophic lateral sclerosis (ALS) cases in the United States and their proximity to multidisciplinary ALS clinics, 2013

Background: Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease that typically results in death within 2–5 years of initial symptom onset. Multidisciplinary ALS clinics (MDCs) have been established to provide specialty care to people living with the disease. Objective: To estimate the proximity of ALS prevalence cases to the nearest MDC in the US to help evaluate one aspect of access to care. Methods: Using 2013 prevalence data from the National ALS Registry, cases were geocoded by city using geographic information system (GIS) software, along with the locations of all MDCs in operation during 2013. Case-to-MDC proximity was calculated and analyzed by sex, race, and age group. Results: During 2013, there were 72 MDCs in operation in 30 different states. A total of 15,633 ALS cases were geocoded and were distributed throughout all 50 states. Of these, 62.6% were male, 77.9% were white, and 76.2% were 50–79 years old. For overall case-to-MDC proximity, nearly half (44.9%) of all geocoded cases in the US lived >50 miles from an MDC, including approximately a quarter who lived >100 miles from an MDC. There was a statistically significant difference between distance to MDC by race and age group. Conclusions: The high percentage of those living more than 50 miles from the nearest specialized clinic underscores one of the many challenges of ALS. Having better access to care, whether at MDCs or through other modalities, is likely key to increasing survivability and obtaining appropriate end-of-life treatment and support for people with ALS.

News from the National ALS Registry

The ALS Registry Act, passed in 2008, authorized establishment of a National ALS Registry with the goals of defining amyotrophic lateral sclerosis (ALS) incidence and prevalence, characterizing ALS patients' demographics, and examining risk factors. The registry uses two sources of data: 80% derives from administrative data (from the Centers for Medicare and Medicaid Services, the Veterans Health Administration and the Veterans Benefits Administration) and 20% from a Web-based portal that patients …

Prevalence of Amyotrophic Lateral Sclerosis - United States, 2012-2013.

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a progressive and fatal neuromuscular disease for which no cure or viable treatment has been identified. ALS, like most noncommunicable diseases, is not a nationally notifiable disease in the United States. The prevalence of ALS in the United States during 2010-2011 was estimated to be 3.9 cases per 100,000 persons in the general population. Updated prevalence estimates are needed to help monitor disease status, better understand etiology, and identify risk factors for ALS. 2012-2013. The National ALS Registry, established in 2009, collects data on ALS patients in the United States to better describe the incidence and prevalence of ALS, examine risk factors such as environmental and occupational exposures, and characterize the demographics of those living with ALS. To identify prevalent cases of ALS, data are compiled from four national administrative databases (maintained by the Centers for Medicare and Medicaid Services, the Veterans Health Administration, and the Veterans Benefits Administration). To identify cases not included in these databases and to better understand risk-factors associated with ALS and disease progression, the Registry also includes data that are collected from patients who voluntarily enroll and complete online surveys. During 2012 and 2013, the Registry identified 14,713 and 15,908 persons, respectively, who met the surveillance case definition of ALS. The estimated ALS prevalence rate was 4.7 cases per 100,000 U.S. population for 2012 and 5.0 per 100,000 for 2013. Due to revisions to the algorithm and use of death data from the National Death Index, an updated prevalence estimate has been calculated retrospectively for October 19, 2010-December 31, 2011. This updated estimate showed a prevalence rate of 4.3 per 100,000 population and a total of 13,282 cases. Since the inception of the Registry, the pattern of characteristics (e.g., age, sex, and race/ethnicity) among persons with ALS have remained unchanged. Overall, ALS was more common among whites, males, and persons aged 60-69 years. The age groups with the lowest number of ALS cases were persons aged 18-39 years and those aged ≥80 years. Males had a higher prevalence rate of ALS than females overall and across all data sources. These findings remained consistent during October 2010-December 2013. The Registry is the only available data source that can be used to estimate the national prevalence for ALS in the United States. Use of both administrative national databases and self-report from patients enables a comprehensive approach to estimate ALS prevalence. The overall increase in the prevalence rate from 4.3 per 100,000 persons (revised) during 2010-2011 to 4.7 and 5.0 per 100,000 persons, respectively, during 2012-2013 likely is not an actual increase in the number of ALS cases. Rather, this increase might be attributed to improved case ascertainment due to the refinement of the algorithm used to identify definite ALS cases, along with an increased public awareness of the Registry. Registry estimates of ALS prevalence are consistent with findings from long-established ALS registries in Europe and from smaller-scale epidemiologic studies previously conducted in the United States. Data collected by the National ALS Registry are being used to better describe the epidemiology of ALS in the United States and to help facilitate research. The combined approach of using national administrative databases and a self-enrollment web portal to collect data is novel and potentially could be used for other non-notifiable diseases such as Parkinson's disease or multiple sclerosis. Increased public awareness of the Registry might lead to more ALS cases being identified from the secure web portal (https://www.cdc.gov/als), which can ascertain cases apart from the national administrative databases. For example, in 2014, the ALS Ice Bucket Challenge, a social media-centered campaign, received extensive public visibility and created increased awareness of ALS. The Agency for Toxic Substances and Disease Registry (ATSDR) works closely with ALS advocacy and support groups, researchers, health care professionals, and others to promote the National ALS Registry and to identify all cases of ALS in the United States. In addition to estimating the prevalence of ALS, the Registry is being used to collect specimens from patient enrollees through a new biorepository, connect patient enrollees with new clinical trials and epidemiologic studies, and fund studies to help learn more about the etiology of ALS. Additional information about the National ALS Registry is available at http://www.cdc.gov/als or by calling toll-free at 1-877-442-9719.

Preliminary Results of National Amyotrophic Lateral Sclerosis (ALS) Registry Risk Factor Survey Data.

BackgroundThe National ALS Registry is made up of two components to capture amyotrophic lateral sclerosis (ALS) cases: national administrative databases (Medicare, Medicaid, Veterans Health Administration and Veterans Benefits Administration) and self-identified cases captured by the Registry’s web portal. This study describes self-reported characteristics of U.S. adults with ALS using the data collected by the National ALS Registry web portal risk factor surveys only from October 19, 2010 through December 31, 2013.ObjectiveTo describe findings from the National ALS Registry’s web portal risk factor surveys.MeasurementsThe prevalence of select risk factors among adults with ALS was determined by calculating the frequencies of select risk factors—smoking and alcohol (non, current and former) histories, military service and occupational history, and family history of neurodegenerative diseases such as ALS, Alzheimer’s and/or Parkinson’s.ResultsNearly half of survey respondents were ever smokers compared with nearly 41% of adults nationally. Most respondents were ever drinkers which is comparable to national estimates. The majority were light drinkers. Nearly one-quarter of survey respondents were veterans compared with roughly 9% of US adults nationally. Most respondents were retired or disabled. The industries in which respondents were employed for the longest time were Professional and Scientific and Technical Services. When family history of neurodegenerative diseases in first degree relatives was evaluated against our comparison group, the rates of ALS were similar, but were higher for Parkinson’s disease, Alzheimer’s disease and any neurodegenerative diseases.ConclusionsThe National ALS Registry web portal, to our knowledge, is the largest, most geographically diverse collection of risk factor data about adults living with ALS. Various characteristics were consistent with other published studies on ALS risk factors and will allow researchers to generate hypotheses for future research.

Using the National Amyotrophic Lateral Sclerosis Registry as a Subject Recruitment Tool for Research (P5.077)

Using the National Amyotrophic Lateral Sclerosis Registry as a Subject Recruitment Tool for Research (P5.077)

Feasibility of creating a National ALS Registry using administrative data in the United States

Uncertainty about the incidence and prevalence of amyotrophic lateral sclerosis (ALS), as well as the role of the environment in the etiology of ALS, supports the need for a surveillance system/registry for this disease. Our aim was to evaluate the feasibility of using existing administrative data to identify cases of ALS. The Agency for Toxic Substances and Disease Registry (ATSDR) funded four pilot projects at tertiary care facilities for ALS, HMOs, and state based organizations. Data from Medicare, Medicaid, the Veterans Health Administration, and Veterans Benefits Administration were matched to data available from site-specific administrative and clinical databases for a five-year time-period (1 January 2001–31 December 2005). Review of information in the medical records by a neurologist was considered the gold standard for determining an ALS case. We developed an algorithm using variables from the administrative data that identified true cases of ALS (verified by a neurologist). Individuals could be categorized into ALS, possible ALS, and not ALS. The best algorithm had sensitivity of 87% and specificity of 85%. We concluded that administrative data can be used to develop a surveillance system/registry for ALS. These methods can be explored for creating surveillance systems for other neurodegenerative diseases.

Current pathways for epidemiological research in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease. The current status of the epidemiology, challenges to its study, and novel study design options are discussed in this paper. We focus on recent results from large-scale population based prospective studies, case-control studies and population based registries, risk factors, and neuropathologic findings in chronic traumatic encephalomyelopathy. We identify areas of interest for future research, including time-trends in the incidence and prevalence of ALS; the meaning of lifetime risk; the phenotypic description of ALS; the definition of familial versus sporadic ALS, syndromic aspects of ALS; specific risk factors such as military service, life style factors such as smoking, the use of statins, and the presence of β-N-methylamino-L-alanine (BMAA), an excitotoxic amino acid derivative possibly produced by cyanobacteria found in almost every terrestrial and aquatic habitat; the emergence and disappearance of an endemic ALS in areas of the Pacific; and gene-environment interactions in the etiology of ALS. To move the epidemiology forward, we suggest using well-characterized cohorts of newly diagnosed ALS patients to identify risk and prognostic factors; storing biological material for future studies; building on the National ALS Registry as a resource of future studies; working in multidisciplinary consortia; and addressing the possible early life etiology of ALS.

Utility of Capture-Recapture Methodology to Assess Completeness of Amyotrophic Lateral Sclerosis Case Ascertainment

Background: With the establishment of a national amyotrophic lateral sclerosis (ALS) registry in the United States, methods are needed to ascertain the completeness of case ascertainment, especially in view of the proposal to rely largely on existing data sources. Methods: Data about ALS patients residing in the 5-county metropolitan Atlanta area (within the State of Georgia) from 2001 to 2005 were categorized according to their source – ALS Association, clinical (Emory Healthcare, community neurologist, Veterans Health Administration, Veterans Benefits Administration), Medicare and death certificates. ALS diagnoses were verified using chart review. Capture-recapture analyses were carried out using log-linear modeling, stratified by age and race. Results: The final model (based on 798 cases), which included the 4 main sources and 3 two-way interaction terms, yielded an estimated total population of 880 (95% CI 816–965), indicating that the combination of case-finding methods identified about 90.7% of cases. The estimated 5-year period prevalence is 38.5/100,000 (95% CI 35.66–42.19). Conclusion: This study highlights gaps in data based on existing data sources and illustrates a method for combining data from multiple sources to help facilitate the successful establishment of a US national ALS registry.

Preparing for a U.S. National ALS Registry: Lessons from a pilot project in the State of Georgia

Our objective was to investigate the utility of existing data sources for identifying cases of amyotrophic lateral sclerosis (ALS) and related motor neuron diseases (MND) in the State of Georgia. Data were acquired from Medicare, Medicaid, Veterans Administration, Emory Healthcare, community neurologists, the ALS Association, and mortality records for ALS/MND patients residing in Georgia during 2001-2005. A neurologist used abstracted medical records to verify the diagnosis of ALS/MND. The positive predictive value (PPV) of an ICD code for a verified diagnosis of ALS was estimated. Simple 'rules' were developed to improve PPV. Results showed that a total of 2413 unique potential cases were identified in existing data sources. Medical records of 579 cases were available for review; the diagnosis of ALS (or a related MND) was confirmed in 486 (PPV = 84%) cases. Predictive rules, which permitted classification of ∼80% of the chart-reviewed population, improved PPV to 96-98%. In conclusion, existing data sources are useful for identifying cases of ALS/MND; most data sources contribute a substantial number of unique cases. Predictive algorithms may permit correct classification of a large proportion of cases without the need for verification based on medical record review.