What do you think caused your ALS? An analysis of the CDC national amyotrophic lateral sclerosis patient registry qualitative risk factor data using artificial intelligence and qualitative methodology

Figures & data

Table 2. Topics identified by artificial intelligence for responses to question, ‘What do you think caused your ALS?’

Topic Clusters from responses	n	%
Ungrouped	1,859	60.7
Unknown	499	16.3
Family history of other neurological disease	137	4.5
Heredity	135	4.4
Diet/Exercise	69	2.3
Head trauma	57	1.9
Genetics	57	1.9
Military	59	1.9
Concussion	48	1.6
Statins	48	1.6
Stress	47	1.5
Chemical exposure	46	1.5

*Ungrouped cluster reflects responses that did not fit into the top responses.

Table 3. Comparison of top artificial intelligence (AI) topics and qualitative analysis themes, with sample responses from persons with ALS.

AI topic cluster	Corresponding qualitative analysis main theme	Qualitative analysis subtheme 1 (if applicable)	Qualitative analysis subtheme 2 (if applicable)	Sample response
Chemical exposure	Environment/exposure to chemicals/pesticides		Broadly defined, no specific incident	“modified food, air quality, water quality…”
	Environment/exposure to chemicals/pesticides		Specific incident recalled	“Possible exposure to antifungal or pesticides in yard o exposure to chlorine (swimming pools).”
	Exposure to metals/mercury			“I played with mercury from broken thermometers occasionally as a child.”
	Occupational/non-agricultural, nonmilitary		Broad/Long-term exposures	“The exposure to non-lead and lead paint happened while marking timber working for the US Forest Service. The lead based paint was used I believe until the early to mid 1990s. I started in 1987 so I was exposed to lead based paint for a few years. We would not use any facemask or protective breathing device and many times our faces would be the color of the paint we would be using, inhaling the paint.”
			Firefighting	“There are several factors I believe could have caused The ALS. The first would be that I was a firefighter for 30 years I was exposed During numerous fires to toxic smoke from structure fires vehicle fires and wildland fires. During the early part of my career we did not have and use breathing apparatus like we do in modern firefighting. Even today after 30 years of firefighting there is still no breathing apparatus for wildland firefighters.”
	Agricultural/farming			“For me, it was doing a lot of manual labor work on my new farm, fencing, using chemicals, and working too hard every evening and after work.”
Diet/Exercise	Lifestyle	Drugs/alcohol		“Perhaps my beer drinking (2-3 beers/day), but I don’t like to get drunk. For now, the past few months, I have given up beer. I don’t drink wine or hard liquor.” “as a teen and in my early 20's I did several illegal drugs, and wondered if it had any bearing on the disease, I did paper acid 3 times, alot of marijauna, and cocaine. I drank heavily during my early twenties as well.”
		Smoking		“I was a moderate smoker (5-10 cigarettes per day) from age 19 to age 39.”
		Diet		“I also drank 5-6 diet sodas every day for 25 years. I have to wonder if those chemicals did something.”
		Exercise/sports/athletics/heavy physical labor		“12 hour of exercise in a gym per week”
Family history of other neurological disease	Family history of other neurodegenerative disease			“I am wondering if my Mother’s Dementia (Alzheimers?) and my brother’s Parkinson Disease may be related to my ALS diagnosis. 3 of Mother’s sisters also had Dementia.”
Head trauma	Accident/Injury	With reference to head injury		“…I went over the handlebars on my mountain bike and landed squarely on my head. I hurt my neck quite a bit, but did not seek medical attention. I really thought that I injured something.”
		With no reference to head injury		“I have had several traumatic accidents in my life, I had an accident at work where a stack of 700-800 lbs of cardboard boxes fell on my right leg breaking it in 3 places. I was hit by a train in 2004. I walked away with that with only a sprained ankle.”
Concussion	See head trauma
Genetics	Genetic	General theory of genetic basis for disease with no known family history
		Known genetic cause/family history-testing or gene name was referenced		“I have a mutated SOD1 gene. Three other members of my family have had ALS.”
		Genetic cause - relatives w/ALS or ALS-like disease but no evidence of genetic testing		“caused by familial; possibly from the chemicals I worked with and also the various armaments that the military has (including nuclear).”
Heredity	See Genetics
Unknown	Don’t know/none			“I don’t know.” “Who knows.” “I wish I knew.”
Military	Military	General reference to military service-related exposures		“I can assume it was caused when I deployed to desert storm, I was exposed to burning oil wells, burn pits, drove by vehicles that were destroyed with munitions, setup outside were the Army destroyed a cache of ordnance and took some pills directed by my superiors for possible chemical attack.”
		Immunizations, medications received in military		“I can only speculate that heavy exposure to agent orange in Vietnam, or the rapid vaccination process prior to going to Vietnam, where vaccines were given for a variety of diseases within a 2-week period and should have been spread over a 6 months period, may have been two trigger points for ALS later in life. The vaccines given were for standard immunizations as well as for overseas immunizations for typhoid, paratyphoid, yellow fever, cholera, and plague. While in #ry we were given gamma-globulin and chloroquine. The whole combination is a witches’ brew.”
		Agent Orange		“While in the USAF I was exposed to a variety of different chemicals, fungicides, fuels and classified item, in a confined cargo bay for numerous hours in flight. Also exposed to Agent Orange and other chemicals while serving time in Vietnam.”
		Occupational exposure	Burn pit	“I think it had to do with deployment to Iraq. I never had blood pressure problems until that deployment. Was in #ry 14 months. We had burn pit on site and i ran the fuel truck with jp8 everyday.”
			Nuclear/radiation	“I was stationed at a fort guarding New York Harbor that had a Nike Missile site, with Hercules missiles. It was reputed that they rotated nuclear missiles through at times. My job required me to go all over the post as I was involved in keeping the post running for the Air Defense Artillery unit. It was a very old fort that had old battery installation too. We skated on the cooling ponds.”
Statins	Personal medical history	Medications, non-statins		“I really think what caused it was too much blood pressure medication. Many tests such as CT scan, MRI, for my heart. Also being given Ciprofloxacin. Also I had a nuclear stress test. After all of these things I started having the symptoms of ALS.”
		Statins		“I took High dose statins for more than 10 years…I think the statin use caused myopathy and neuropathy leading to ALS.”
		Surgery or other medical procedure		“I had a total knee surgery in September. I started showing signs in November/December.”
		Chronic comorbidities such as diabetes, arthritis		“The year I had first symptom of ALS I had shingles earlier that year and took medication for the shingles. Also have type two diabetes, and was given insulin that caused extremely low blood sugar. I wonder if those caused it.”
		Virus, like EBV, STDs, meningitis, excluding Lyme		“I have familial ALS- SOD-1 G94A. As for triggers, I had mononucleosis several years prior to developing ALS. My mono caused viral meningitis and I have had low to moderate levels of EBV (Epstein Barr Virus) since recovering from mono/meningitis.”
		Lyme disease		“I have also been around pets and ticks. I wonder how Lyme Disease might cause, mimic or contribute to ALS.”
		Immunizations-not military-related		“I had a vaccine adverse reaction injury caused by my flu vaccine…I believe this triggered my ALS.”
Stress	Emotional stress or trauma			“I believe an extreme amount of stress caused this. I was working with my business partner for several years with great difficulty. Then one day I had had enough and told him I am retiring. This was in the beginning of January and by the end of the month I started with slight drop foot. I had also lost my daughter two years prior to that.”
Ungrouped	Other			“Na” “I have ALS4.” “It is part of God’s plan for my life.”
No corresponding AI theme identified	Nuclear/radiation exposures/nonmilitary			“grew up fifty mile from Nevada above ground nuclear testing site”

*Manual thematic analysis grouped responses into themes and subthemes, which the AI/NLP analysis did not. This allowed for all the ‘ungrouped’ responses identified by AI/NLP to be categorized.

Table 1. National amyotrophic lateral sclerosis (ALS) registry participant characteristics (N = 3,061).

Diagnosis year	n	%
Pre-2011	210	6.9
2011	89	2.9
2012	166	5.4
2013	382	12.5
2014	457	14.9
2015	348	11.4
2016	335	10.9
2017	261	8.5
2018	282	9.2
2019	263	8.6
2020	176	5.8
2021	92	3.0
Diagnosis age (yrs)
<40	93	3.0
40–49	323	10.6
50–59	873	28.5
60–69	1,175	38.4
70–79	525	17.2
≥80	72	2.4
Gender
Male	1,790	58.5
Female	1,271	41.5
Marital status
Never married	134	4.4
Married	2,418	79.2
Separated	26	0.9
Divorced	293	9.6
Widowed	121	4.0
Living with partner	63	2.1
Race
White	2,940	96.0
Non-White	121	4.0
Census region*
1	403	13.4
2	833	27.6
3	1,118	37.0
4	665	22.0
Military history
Yes	583	19.1
No	2,478	80.9
Smoking history
Never smoked	1,750	57.2
Ever smoked	1,311	42.8
Alcohol history
Never drank	594	19.4
Ever drank	2,467	80.6
Family history of ALS
No	2,862	93.5
Yes	199	6.5
Family history of neurological disease
No	2,484	81.5
Yes	565	18.5

*Northeast: Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont; South: Alabama, Arkansas, Delaware, District of Columbia, Florida, Georgia, Kentucky, Louisiana, Maryland, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia, West Virginia; Midwest: Iowa, Illinois, Indiana, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, Ohio, South Dakota, Wisconsin; West: Alaska, Arizona, California, Colorado, Hawaii, Idaho, Montana, Nevada, New Mexico, Oregon, Utah, Washington, Wyoming.

Data availability statement

The data are available via CDC - Amyotrophic Lateral Sclerosis: Research Application Form.