Racial Disparities in the Diagnosis and Prognosis of ALS Patients in the United States

Jaime Raymond1 · Theresa Nair1 · Kelly Graham Gwathmey2 · Theodore Larson1 · D. Kevin Horton1 · Paul Mehta1

Received: 4 January 2024 / Revised: 8 July 2024 / Accepted: 18 July 2024This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024

Abstract

Background Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease with largely unknown etiology. This study compares racial differences in clinical characteristics of ALS patients enrolled in the National ALS Registry (Registry). Methods Data from ALS patients who completed the Registry’s online clinical survey during 2013–2022 were analyzed to determine characteristics such as site of onset, associated symptoms, time of symptom onset to diagnosis, and pharmacologi- cal and non-pharmacological interventions for White, Black, and other race patients.

Results Surveys were completed by 4242 participants. Findings revealed that Black ALS patients were more likely to be diagnosed at a younger age, to have arm or hand initial site of onset, and to experience pneumonia than were White ALS patients. ALS patients of other races were more likely than White ALS patients to be diagnosed at a younger age and to expe- rience twitching. The mean interval between the first sign of weakness and an ALS diagnosis for Black patients was almost 24 months, statistically greater than that of White (p = 0.0374; 16 months) and other race patients (p = 0.0518; 15.8 months). The mean interval between problems with speech until diagnosis was shorter for White patients (6.3 months) than for Black patients (17.7 months) and other race patients (14.8 months).

Conclusions and Relevance Registry data shows racial disparities still exist in the diagnosis and clinical characteristics of ALS patients. Increased recruitment of non-White ALS patients and better characterization of symptom onset between races might aid clinicians in diagnosing ALS sooner, leading to earlier therapeutic interventions.

Introduction

Amyotrophic lateral sclerosis (ALS) is a progressively fatal disease of which the actual pathogenesis and cause(s) remain largely unknown [1]. Recently studies have shown ALS in the United States (U.S.) to be more commonly diagnosed in White males over 60 years of age [2]. Previous epidemio- logic studies addressing racial variation in ALS diagnosis and clinical characteristics have been limited [3, 4]. Global ALS prevalence rates vary widely ranging from 4.1 per 100,000 persons in Norway [5] to 8.4 per 100,000 persons in North-Eastern Italy [6, 7]. The most recent prevalence report in the U.S. estimated an adjusted prevalence rate of 9.1 per 100,000 persons [2]. One population-based study in the southeast part of the U.S. found a prevalence rate of 3.04 per 100,000 persons for the Black population [8].

Clinical characteristics vary widely among patients (e.g., site of onset, progression of the disease) [9]. The diagnosis of ALS can be challenging, with the site of onset resulting in several different phenotypes that include limb-onset, bulbar/ respiratory-onset, or trunk/global onset [10]. Persons with bulbar onset typically have shorter life expectancy versus those with limb onset [11]. Patients typically experience var- ious symptoms during the course of the disease such as mus- cle cramps, twitching (fasciculations), problems with speech (dysarthria), and difficulty swallowing (dysphagia) [12]. To date, only 10% of ALS cases are familial; the remaining cases are considered sporadic [13]. Studies have suggested that genetic, environment, and lifestyle factors play a signifi- cant role in ALS occurrence and phenotype [14–17].

The purpose of this paper is to compare racial differences in clinical characteristics of ALS patients enrolled in the U.S. National ALS Registry (Registry). Because ALS onset and progression among minority races have not been studied widely, these data provide additional information on phe- notypic differences in a national population [12, 17, 18]. Having a better understanding of ALS among non-White patients regarding onset and progression might aid clinicians in making a quicker diagnosis, which could lead to earlier therapeutic interventions and help narrow the disparities, especially access to care, in those populations.

Demographic Survey Module

The demographic survey module was one of the first six mod- ules created for ALS patients to take part in. This module launched on October 19, 2010, when the Registry was initi- ated. Race was defined by standard federal definitions. For this analysis, the categories are White, Black, and other race. If more than one race was chosen, participants were categorized as other race. Body mass index (BMI) was calculated using a standard formula: BMI = weight (lb) / [height (in)]2 × 703 [24]. Other selected demographic characteristics for those who com- pleted the clinical survey module were abstracted, including sex, ethnicity, age at diagnosis, and year registered.

Clinical Symptoms Survey Module

The clinical symptoms survey module was created in part- nership with the ALS Research Group, which includes U.S. and Canadian neurologists and researchers. The purpose of the module is to examine physical symptoms that participants developed before and after an ALS diagnosis. The survey con- tains 54 questions and covers topics such as the site of onset, time of initial symptom onset to diagnosis, and time from diag- nosis to hospice referral. This module was launched in Novem- ber 2013 for new Registry enrollees. Previous enrollees were prompted to return to the web portal to complete this survey.

Data Analysis Methods

Site of onset refers to the body part to which a participant reported their first ALS-related weakness or symptom. The body was divided into 2 groups: (1) limb, which included extremities (hand, arm, foot, or leg), and (2) bulbar, which included speech or swallowing, or trunk/global, which included neck, back or abdominal areas, breathing muscles, or total body weakness. “Other symptoms” were those par- ticipants experienced after the initial symptom and could have occurred before or after diagnosis. The occurrence of symp- toms was determined by calculating the time from symptom onset to diagnosis. Bivariate analyses were performed to exam- ine the associations of race, symptoms following initial onset, and interventions for ALS. Categorical variables were assessed with chi-square tests. Statistical significance was considered at alpha = 0.05. All data analyses were performed using SAS 9.4 [25].

Methods

The National ALS Registry

In October 2010, the Agency for Toxic Substances and Disease Registry (ATSDR), part of the Centers for Disease Control and Prevention (CDC), launched the congression- ally mandated, population-based National ALS Registry to help clarify the epidemiology of ALS in the U.S. [19]. The Registry’s purpose is to quantify the incidence and preva- lence of ALS in the U.S., describe the patient demographics, and examine potential risk factors [20]. Details about the Registry’s objectives are presented elsewhere [21] as are its methods [22]. From there, the national administrative databases and the web portal are merged and de-duplicated to ensure that individuals are not counted twice. To verify ALS status within the web portal, ATSDR adopted the six questions from the U.S. Department of Veterans Affairs ALS registry that have been proven to be reliable indicators for accurate ALS diagnoses [23]. The Registry’s web portal also allows participants to complete brief online surveys about their ALS experience on topics such as occupational and military histories, smoking and alcohol use, and clinical symptoms. Currently, the Registry has 18 survey modules.

Results

From the launch of the Registry in October 2010 through December 31, 2022, 10,894 adults aged 18 years or older self-enrolled via the Registry’s online portal and completed at least one of the 18 surveys. Of these persons, 4242 (38.9%) completed the clinical survey module, which didn’t launch until November 1, 2013, as well as the basic demographic survey module. Of those who responded to both surveys, 96% self-reported as White. Only 73 patients self-reported as Black, and 92 patients were classified as other races (e.g., Chinese, Native American). In the other race category, the majority self-reported themselves as Asian (62%). Table 1 lists the demographic characteristics of these 4242 patients, stratified by race. More than 26% of the Black patients were diagnosed with ALS before age 50 years, compared with only 12.9% of White patients (p = 0.0067). That was also true for a higher percentage of patients of other races (19.6% vs 12.9%, p = 0.0070). Other race patients also had a higher percentage of being at a normal BMI at the time of reg- istration than did White ALS patients (44.6% vs. 34.7%, p = 0.0453). Lastly, other race ALS patients were less likely to have served in the military, compared with White ALS patients (8.7% vs. 18.3%, p = 0.0176). Black race patients did not see the same differences as other race patients.

Table 2 shows the site of onset among the 4242 patients, stratified by race. All patients who answered the question regarding the site of onset reported having progressivemuscle weakness before the ALS diagnosis. More than 70% of the patients (n = 3015) had limb onset. A significantly higher proportion of Black patients had hand or arm onset weakness compared to White patients (p = 0.0012). Almost 29% of the 4242 patients experienced bulbar or global onset; of those, Black patients were slightly less likely to have bul- bar or global onset than were White patients (p = 0.0690).

Table 3 shows some of the other symptoms experienced by ALS patients. The most frequent symptoms during the course of the disease included muscle cramps (57.5%), twitching (56.4%), and problems with speech (35.6%). Among the 4242 patients, 24.9% had difficulty swallowing, and 22.6% experienced trips or falls. Almost 13% of partici- pants had difficulty controlling bowels, 12.2% had experi- enced pneumonia, and 5.6% experienced blood clots. Com- pared with White patients, when stratified by race, a higher proportion of Black patients reported suffering from pneu- monia (p = 0.0067) and those of other races saw a slightly higher proportion of twitching (p = 0.0582).

The time between symptom onset and ALS diagnosis was calculated for each symptom and stratified by race (Fig. 1). White and other race patients saw muscle weakness onset approximately 16 months before an ALS diagnosis; Black patients showed a mean time of almost 24 months before diagnosis (p = 0.0374). Of the 1470 patients with onset of speech problems, the mean time to ALS diagnosis was approximately 6 months for White patients, about 16 months

for Black patients, and 18 months for other race patients. Bowel issues preceded an ALS diagnosis by approximately 3 months for patients of other races, but almost 13 months for White patients, and 15 months for Black patients.

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