Global Barriers to the Diagnosis of Multiple Sclerosis: Data From the Multiple Sclerosis International Federation Atlas of MS, Third Edition.

BACKGROUND AND OBJECTIVES: Recent data suggest increasing global prevalence of multiple sclerosis (MS). Early diagnosis of MS reduces the burden of disability-adjusted life years and associated health care costs. Yet diagnostic delays persist in MS care and even within national health care systems with robust resources, comprehensive registries, and MS subspecialist referral networks. The global prevalence and characteristics of barriers to expedited MS diagnosis, particularly in resource-restricted regions, have not been extensively studied. Recent revisions to MS diagnostic criteria demonstrate potential to facilitate earlier diagnosis, but global implementation remains largely unknown. METHODS: The Multiple Sclerosis International Federation third edition of the Atlas of MS was a survey that assessed the current global state of diagnosis including adoption of MS diagnostic criteria; barriers to diagnosis with respect to the patient, health care provider, and health system; and existence of national guidelines or national standards for speed of MS diagnosis. RESULTS: Coordinators from 107 countries (representing approximately 82% of the world population), participated. Eighty-three percent reported at least 1 "major barrier" to early MS diagnosis. The most frequently reported barriers included the following: "lack of awareness of MS symptoms among general public" (68%), "lack of awareness of MS symptoms among health care professionals" (59%), and "lack of availability of health care professionals with knowledge to diagnose MS" (44%). One-third reported lack of "specialist medical equipment or diagnostic tests." Thirty-four percent reported the use of only 2017 McDonald criteria (McD-C) for diagnosis, and 79% reported 2017 McD-C as the "most commonly used criteria." Sixty-six percent reported at least 1 barrier to the adoption of 2017 McD-C, including "neurologists lack awareness or training" by 45%. There was no significant association between national guidelines pertaining to MS diagnosis or practice standards addressing the speed of diagnosis and presence of barriers to early MS diagnosis and implementation of 2017 McD-C. DISCUSSION: This study finds pervasive consistent global barriers to early diagnosis of MS. While these barriers reflected a lack of resources in many countries, data also suggest that interventions designed to develop and implement accessible education and training can provide cost-effective opportunities to improve access to early MS diagnosis.

Impact of the National Amyotrophic Lateral Sclerosis Registry: Analysis of Registry-funded Research.

OBJECTIVE: This research aims to examine the impact of the National Amyotrophic Lateral Sclerosis (ALS) Registry-funded research activities. METHODS: Registry-funded research and related publications were identified through the National ALS Registry website, the National Institutes of Health (NIH) Reporter website, and verified by Principal Investigators. Key study characteristics (e.g., study population, sample size) and key impact features (e.g., risk factors) were abstracted and recorded on study abstraction forms. Descriptive statistics were used to analyze the volume, productivity, and findings of the Registry-funded research. RESULTS: Since 2012, the National ALS Registry funded 21 research projects. Of these, 14 were through extramural research grants and included in the analysis. These studies are often related to environmental, medical conditions, and genetic risk factors. On average, the funded grants produced 1 to 2 publications which were cited 114 times by other researchers. The relative citation ratio averaged 1.81 with a weighted relative citation ratio of 16.28. These studies supported the identification and confirmation of candidate risk factors. Environmental and occupational risk factors typically related to heavy metal exposure (e.g., lead, mercury) and agricultural chemicals (e.g., pesticides, herbicides), and the occupations associated with exposure to these substances were most frequently explored. INTERPRETATION: The National ALS Registry is a multifaceted research platform, one component of which is funded research. This Registry-funded research fills an essential gap in the overall ALS scientific community as it is difficult to prevent and treat a disease without a deeper understanding of its causes.

Analysis of Biospecimen Demand and Utilization of Samples from the National Amyotrophic Lateral Sclerosis Biorepository.

Amyotrophic lateral sclerosis (ALS) is a rare neurological condition affecting upper and lower motor neurons. The National ALS Biorepository (referred to as the Biorepository) was initiated in 2015, with biospecimen collection beginning in 2017, as a repository for biospecimens for future ALS research. To help ensure the usefulness of the Biorepository, a biospecimen demand analysis is conducted on an annual basis, as well as an analysis of the utilization of the Biorepository. To determine the types of biospecimens to be collected for the Biorepository, an in-depth initial examination occurred followed by ongoing biospecimen demand and utilization analyses. The initial examination included input from an expert panel, discussions with ALS research experts, review of other ALS biorepositories, assessment of biospecimen demand, and analysis of the biospecimen types historically used in ALS research. Of all biospecimen types reported in the literature, the most frequently used were DNA, postmortem spinal cord, blood, and cerebrospinal fluid; while the frequently reported types of biospecimens used in ALS-related grants were induced pluripotent stem cells, brain, blood, and spinal cord. Continuous analysis of potential sample demand and tissues collected, based on an analysis of the literature and funded grants, and actual sample requests can assist the Biorepository in ensuring that the appropriate samples are available for researchers when they are needed.

Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition.

BACKGROUND: High-quality epidemiologic data worldwide are needed to improve our understanding of disease risk, support health policy to meet the diverse needs of people with multiple sclerosis (MS) and support advocacy efforts. OBJECTIVES: The Atlas of MS is an open-source global compendium of data regarding the epidemiology of MS and the availability of resources for people with MS reported at country, regional and global levels. METHODS: Country representatives reported epidemiologic data and their sources via survey between September 2019 and March 2020, covering prevalence and incidence in males, females and children, and age and MS type at diagnosis. Regional analyses and comparisons with 2013 data were conducted. RESULTS: A total of 2.8 million people are estimated to live with MS worldwide (35.9 per 100,000 population). MS prevalence has increased in every world region since 2013 but gaps in prevalence estimates persist. The pooled incidence rate across 75 reporting countries is 2.1 per 100,000 persons/year, and the mean age of diagnosis is 32 years. Females are twice as likely to live with MS as males. CONCLUSIONS: The global prevalence of MS has risen since 2013, but good surveillance data is not universal. Action is needed by multiple stakeholders to close knowledge gaps.

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.

State and metropolitan area-based amyotrophic lateral sclerosis (ALS) surveillance.

UNLABELLED: Our objective was to develop state and metropolitan area-based surveillance projects to describe the characteristics of those with ALS and to assist with evaluating the completeness of the National ALS Registry. Because the literature suggested that ethnic/racial minorities have lower incidence of ALS, three state and eight metropolitan areas were selected to over-represent ethnic/racial minorities to have a sufficient number of minority patients. Project activities relied on reports from medical providers and medical records abstraction. The project areas represented approximately 27% of the U.S. POPULATION: The combined racial and ethnic distribution of these areas is 64.4% white, 16.0% African-American, 6.7% Asian, and 28.3% Hispanic. Most neurologists did not diagnose or provide care for ALS patients. The number of unique patients reported was close to expected (5883 vs. 6673). Age and gender distribution of patients was similar to the literature. The crude average annual incidence rate was 1.52 per 100,000 person-years, CI 1.44-1.61, and the 2009 prevalence rate was 3.84 per 100,000 population, CI 3.70-3.97. In conclusion, this study represents the largest number of clinically diagnosed ALS patients reported by neurologists in the U.S. Comparison of these data with those in the National ALS Registry will help evaluate the completeness of administrative databases.

Updated Prevalence and Demographic Characteristics for ALS Cases in Texas, 2009-2011.

OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a rare motor neuron disease with incidence rates ranging from 1 to 2/100,000 person-years. The Texas Department of State Health Services previously conducted surveillance for ALS in three metropolitan areas of Texas. This project provides an update to this research, while expanding its scope to the entire state. METHODS: The Texas Department of State Health Services contacted neurologists throughout Texas to determine whether they diagnose or treat patients with ALS. Those neurologists who cared for Texas residents with ALS between 2009 and 2011 were asked to complete a one-page case reporting form for each patient. RESULTS: A total of 1422 unique cases were received. The average crude annual incidence rate was 1.30/100,000 person-years and the 2009 period prevalence rate was 2.92/100,000 individuals. Reported cases were most likely to be 60 to 69 years old, non-Hispanic, white, and men. CONCLUSIONS: This project provides an update to previously published Texas-specific epidemiological data regarding ALS; also, we note that our findings are consistent with previously published studies.

Geographic Variation of Amyotrophic Lateral Sclerosis Incidence in New Jersey, 2009-2011.

Few analyses in the United States have examined geographic variation and socioeconomic disparities in amyotrophic lateral sclerosis (ALS) incidence, because of lack of population-based incidence data. In this analysis, we used population-based ALS data to identify whether ALS incidence clusters geographically and to determine whether ALS risk varies by area-based socioeconomic status (SES). This study included 493 incident ALS cases diagnosed (via El Escorial criteria) in New Jersey between 2009 and 2011. Geographic variation and clustering of ALS incidence was assessed using a spatial scan statistic and Bayesian geoadditive models. Poisson regression was used to estimate the associations between ALS risk and SES based on census-tract median income while controlling for age, sex, and race. ALS incidence varied across and within counties, but there were no statistically significant geographic clusters. SES was associated with ALS incidence. After adjustment for age, sex, and race, the relative risk of ALS was significantly higher (relative risk (RR) = 1.37, 95% confidence interval (CI): 1.02, 1.82) in the highest income quartile than in the lowest. The relative risk of ALS was significantly lower among blacks (RR = 0.57, 95% CI: 0.39, 0.83) and Asians (RR = 0.63, 95% CI: 0.41, 0.97) than among whites. Our findings suggest that ALS incidence in New Jersey appears to be associated with SES and race.

Effects of demographic factors on survival time after a diagnosis of amyotrophic lateral sclerosis.

BACKGROUND: The Agency for Toxic Substances and Disease Registry established surveillance projects to determine the incidence, prevalence, and demographic characteristics of persons with Amyotrophic Lateral Sclerosis (ALS) in defined geographic areas. There is a need to characterize and account for the survival and prognostic factors among a population-based cohort of ALS cases in the United States. METHODS: A cohort of incident cases diagnosed from 2009-2011 in New Jersey was followed until death or December 31, 2013, whichever happened first. Survival was assessed using Kaplan-Meier curves and Cox proportional hazards regression was used to identify prognostic factors. RESULTS: Sixty-four percent of incident cases died between 2009 and 2013, 93.7% specifically from ALS. Among the 456 cases studied in the survival analysis, the median survival from diagnosis was 21 months; 46% of cases survived longer than two years from diagnosis. Older age predicted shorter survival. While there is some indication of differences because of sex, race, and ethnicity, these differences were not statistically significant when accounting for age. CONCLUSIONS: New Jersey mortality data were queried to determine the vital status of a cohort of incident ALS cases and used to investigate relationships between demographic factors and survival. Results are consistent with other population-based studies. Older age was a strong predictor of shorter survival time. Additional follow-up time is needed to characterize longer-term survival.

Amyotrophic lateral sclerosis surveillance in Baltimore and Philadelphia.

INTRODUCTION: Limited epidemiological data on amyotrophic lateral sclerosis (ALS) exist in defined geographic areas in the United States. METHODS: Neurologists submitted case reports for patients under their care between January 1, 2009, and December 31, 2011, who met the El Escorial criteria. Diagnosis was confirmed for a sample of cases by the consulting neurologist. Death certificate data were used for supplemental case identification. RESULTS: The 248 reported cases were most likely to be 50-69 years old, men, white, and non-Hispanic. The total crude average annual incidence rate was 1.46 per 100,000 person-years. CONCLUSIONS: The reported demographic characteristics were consistent with previously published findings. The crude annual incidence was slightly lower than the expected rate of 1.6 but was within the range reported previously (0.7-2.5). These findings help quantify the burden of ALS in the United States.

Racial and ethnic differences among amyotrophic lateral sclerosis cases in the United States.

Our objective was to describe racial and ethnic differences of amyotrophic lateral sclerosis (ALS) in distinct geographic locations around the United States (U.S.). ALS cases for the period 2009-2011 were identified using active case surveillance in three states and eight metropolitan areas. Of the 5883 unique ALS cases identified, 74.8% were white, 9.3% were African-American/black, 3.6% were Asian, 12.0% were an unknown race, and 0.3% were marked as some other race. For ethnicity, 77.5% were defined as non-Hispanic, 10.8% Hispanic, and 11.7% were of unknown ethnicity. The overall crude average annual incidence rate was 1.52 per 100,000 person-years and the rate differed by race and ethnicity. The overall age-adjusted average annual incidence rate was 1.44 per 100,000 person-years and the age-adjusted average incidence rates also differed by race and ethnicity. Racial differences were also found in payer type, time from symptom onset to diagnosis, reported El Escorial criteria, and age at diagnosis. In conclusion, calculated incidence rates demonstrate that ALS occurs less frequently in African-American/blacks and Asians compared to whites, and less frequently in Hispanics compared to non-Hispanics in the U.S. A more precise understanding of racial and ethnic variations in ALS may help to reveal candidates for further studies of disease etiology and disease progression.

Population-based surveillance of amyotrophic lateral sclerosis in New Jersey, 2009-2011.

BACKGROUND: Limited epidemiological data exist about amyotrophic lateral sclerosis (ALS) in the United States (US). The Agency for Toxic Substances and Disease Registry maintains the National ALS Registry and funded state and metropolitan surveillance projects to obtain reliable, timely information about ALS in defined geographic areas. METHODS: Neurologists submitted case reports for ALS patients under their care between January 1, 2009 and December 31, 2011 who were New Jersey residents. A medical record verification form and electromyogram (EMG) report were requested for a sample of case reports. Incidence rates were standardized to the 2000 US Standard Population. RESULTS: The average crude annual incidence rate was 1.87 per 100,000 person-years, the average age-adjusted annual incidence rate was 1.67 per 100,000 person-years, and the point prevalence rate on December 31, 2011 was 4.40 per 100,000 persons. Average annual incidence rates and point prevalence rates were statistically higher for men compared with women; Whites compared with Blacks/African Americans and Asians; and non-Hispanics compared with Hispanics. CONCLUSIONS: The project findings contribute new, population-based, state-specific information to epidemiological data regarding ALS. The findings are generally consistent with previously published surveillance studies conducted in the US and abroad.