Supplemental Digital Content 3. Supplemental Table1: Summary of included articles related to lead exposure.
Author,
Year,
Country
(Ref no.)
Campbell,
1970,
UK
(2)
Type
of
Study
Casecontrol
Chancellor,
1993,
England
(3)
Casecontrol
Deapen,
1986, USA
(4)
Casecontrol
Gresham,
1986, USA
(5)
Casecontrol
Subject recruitment and case ascertainment
1. 74 patients attending two centres (Bristol
and Bath) after June 1965 in whom a diagnosis
of motor neuron disease (MND) had been
made.
2. A control series, matched for age and sex,
was obtained from consecutive admissions to a
general medical ward; these patients were
interviewed in an identical manner as the
cases.
1. Patients with incident MND were identified
from the Scottish Motor Neuron Disease
Register after 1 January 1989 using multiple
methods of case ascertainment and
standardized diagnostic criteria. 147 sALS
patients diagnosed between 1 May 1990 and
31 October 1991, 39 had died before approach
was possible.
2. Controls were matched by sex, age, and
place of residence.
1. Across the United States via a questionnaire
mailed to all patients who voluntarily
contacted the US ALS society, or by clinicians
in private or public clinics who distributed the
questionnaires to patients with ALS. By
March of 1977, 1,643 patients had returned the
questionnaires. The 792 patients still living
were mailed new questionnaires to collect
additional risk factor information, and provide
a list of potential controls who were
acquaintances of the patients prior to the
diagnosis, and of the same gender and age (±5
years).
2. Of the 792 patients, 678 completed the
questionnaire. For controls, of the 678
contacted, 518 returned the questionnaires.
1. Identified 76 ALS cases, of which 66 cases
participated in the study.
2. Cases were ascertained primarily through a
neurology support and research clinic.
3. Identified 66 neighbours/friends of the
patients, all of whom participated.
4.50% males in both groups.
5. Recruited from January – May, 1985.
Population characteristics
Exposure and risk estimates
Score
1. 74 cases and matched 74 controls by
sex and age.
2. 51 males and 23 females (cases and
controls combined).
3. Average age for males and females
was 56.8 and 56.2 years, respectively.
Exposure to lead:
1. A full clinical, occupational, and environmental history was
obtained by means of a standardized questionnaire.
2. A total of 11 and 12 cases were classed into severe exposure
(lead poisoning) and light contact (history only), while 4 and 12
controls were classed into severe and light exposure to lead,
respectively.
6
The age and sex of cases and controls
were identical, a result of the matching
process. There were 61 men (mean age
63, range 35-85 years) and 42 women
(mean age 67, range 28-86 years).
Exposure to lead:
1. A lifetime occupational history questionnaire was used to
ascertain regular lead contact for periods of over 12 months.
2. Exposure to lead among cases and controls: case/control both,
2; case only, 17; control only, 3; neither, 81. OR=5.7(1.630).
3. Exposed/unexposed cases=19/84, exposed/unexposed
controls=5/98.
7
1. 518 cases, 518 controls.
2. 65% males, 98% white, average age
53.3 years.
3. The remaining (unused cases)1,125
patients had similar characteristics
(61%, 96%, and 56.1 years,
respectively)
Exposure to lead:
1. Detailed lifetime occupational histories, including exposure to
lead, were ascertained via questionnaire.
2. Exposed to lead (exposed/unexposed): cases=30/488,
controls=27/491, OR=1.1(0.6-1.9)
8
1. Mean age (SD, range): 59 years
(11.70, 26-84) among cases, 61.5
(11.40, 31-83) among controls.
2. 97% were white in both groups
3. There was no difference between
cases and controls with regard to twin
status, military service, marital status, or
level of education.
Exposure to lead or mercury:
1. The self-administered questionnaire captured employment
information based on NIOSH job categories to probe potential
exposure to nine heavy metals including lead.
2. No difference in exposure was observed with regard to heavy
metals. Lead (unexposed/exposed): cases=50/16,
controls=54/12.
Mercury (unexposed/exposed): cases=59/7, controls=60/6.
7
1
4. Did not mention smoking and alcohol
use, or lifestyle related factors.
Kamel,
2002, USA
(6)
Casecontrol
McGuire,
1997, USA
(7)
Casecontrol
PierceRuhland,
1981,
USA
(8)
Casecontrol
1. All study participants (cases and controls)
were recruited between 1993 and 1996.
2. Cases were required to live in New England
for at least half of the year, be mentally
competent, and speak English.
3. 71% of eligible cases participated in the
study (n = 111). About 85% of the cases were
enrolled within 1 year after diagnosis and the
remainder within 2 years.
4. Population controls with no neurological
diseases were identified through random
telephone screening and matched on sex, age
(30–55, 56–65, and 66–80 years) and region.
354 eligible controls were contacted, 270
(76%) were enrolled, and 256 completed the
entire questionnaire.
1. Recruited during the period 1990-1994.
2. ALS cases aged l8 or older years who were
newly diagnosed with ALS in western
Washington State were identified through a
surveillance system; cases who did not have a
telephone or did not speak English were
excluded.
3. 174 of 180 eligible cases agreed to
participate.
4.Two controls matched to each case according
to sex and age (±5 years) were identified from
the study counties using random telephone
dialling; for controls over 65 years of age,
Medicare eligibility lists for the target counties
were used. The overall response rate was 75%.
No differences were noted cases and
controls with regard to age, sex ratio,
and level of education.
1. 88 living patients were identified from
hospital records, of which 80 participated the
study.
2. Patients’ friends of the same sex and age
matched within 5 years were suggested by the
patients. 80 controls were contacted, 78
controls participated.
1. 80 cases: 53 men, 27 women
2. 78 controls: 52 men, 26 women.
3. Mean age at interview (62 years) was
the same in both groups. .
1. Cases=174, controls=348.
2. Men: cases=95, controls=190,
accounting for 54.6% of participants. .
3. White: cases=164, controls=329,,
accounting for 94.3% and 94.5% of
cases and controls, respectively.
4. Although the average age was not
specified, the age range was similar
among cases and controls..
5. No differences in marital status were
apparent.
6. Differences in education (low/high)
were noted: cases=83/91,
controls=124/224.
2
3. Exposure to lead/mercury in case-control pairs
(cases/controls, +=yes, -=no):
lead/mercury: +/+=6, +/-=13, -/+=6, -/-=8; OR=2.20(0.69-7.47).
Lead: +/+=5, +/-= 12, -/+=6, -/-=10; OR=2.00 (0.63-7.00).
Mercury: +/+= 2, +/-=6, -/+=4, -/-=21; OR=1.50 (0.31-8.26).
Exposure to lead:
1. Occupational history information was obtained via interview.
Duration of occupational exposure to lead was categorized into
four levels (0, 1–399,400–1,999, and 2,000 days of exposure).
Blood lead levels were also measured.
2. ALS risk was increased due to lead occupational exposure.
Study participant exposures (unexposed/exposed) were:
cases=67/35, controls=193/54. OR=1.9 (1.1-3.3).
3. A linear dose dependent increase in risk was observed: exp=0
days, OR=1 (reference category); exp=1-399 days, OR=1.6;
exp=400-1999 days, OR=1.9; exp>=2000 days, OR=2.3, p for
trend=0.02.
4. Mean (SD) blood lead levels were higher in ALS patients:
cases=5.2(0.4), controls=3.4(0.4) µg/dl (P<0.05). Elevated
blood lead levels were associated with an increased ALS r(up to
10 fold per µg/dl lead ).
Exposure to lead -heavy metals:
1. Occupational histories and exposure to specific metals were
ascertained by interview. Lead exposure information was based
on self-reported exposure to specific metals or estimated via
expert review of the occupational history.
1.1. Exposure to lead (self-reported, both sexes, exp/unexp):
cases=21/153, controls=24/324, OR=1.9(1.0-3.6).
1.2. Exposure to lead (panel-estimated, both sexes, exp/unexp):
cases=17/157, controls=31/317, OR=1.1(0.6-2.1).
2. Exposure to heavy metals:
2.1. Self-reported, both sexes, exp/unexp): cases=84/87,
controls=139/209, OR=1.6(1.0-2.5).
2.2. Panel-estimated, both sexes, exp/unexp): cases=49/124,
controls=82/266, OR=1.2(0.8-1.9).
2.3. Self-reported, males, exp/unexp): cases=63/31,
controls=117/73, OR=1.2(0.7-2.1).
2.4. Panel-estimated, males, exp/unexp ): cases=45/49,
controls=67/123, OR=1.5(0.9-2.6).
2.5. Self-reported, females, exp/unexp ): cases=21/56,
controls=22/138, OR=2.3(1.1-4.7).
2.6. Panel-estimated, females, exp/unexp): cases=4/75,
controls=15/143, OR=0.5(0.2-1.4).
Exposure to lead and heavy metals
1. Lead exposure information was based on a telephone
administered occupational questionnaire. Individuals with
exposure durations less than or greater than one year were
considered unexposed or exposed, respectively.
2. Lead (unexposed/exposed): cases=60/20, controls=67/11,
OR=2.03(1.22-2.84),p=0.085.
13
10
6
Yu, 2014,
USA
(9)
Casecontrol
Binazzi,
2009, Italy
(10)
Casecontrol
Morahan,
2006,
Australia
(11)
Casecontrol
Provinciali,
1990, Italy
(12)
Casecontrol
RoelofsIverson,
1984, USA
(13)
Casecontrol
Feychting ,
2003,
Sweden
Cohort
Study
1. ALS subjects were recruited through the
University of Michigan ALS Clinic. Subjects
were over 18 years of age, and had possible,
probable, probable, or definite ALS according
to the revised El Escorial criteria.
2. Age- and gender-matched controls were
recruited through postings on a University. of
Michigan website. Age was matched by
decade
1. Recruited from July 17, 2005 to July 6,
2007. 77 patients, including 70 definite and 7
probable ALS cases; 44 spinal/ 32 bulbar.
2. Diagnosed based on EI Escorial criteria.
2. Relatives or accompanying persons of
outpatients affected by neurological diseases
other than ALS, and coming to the same
hospital ambulatories, served as population
controls.
3. Response rates not indicated.
1. 179 SALS cases. Cases have donated DNA
samples to Australian MND banks, and were
recruited by the MND association. More than
90% of ALS patients nationwide have been
recruited into this bank.
2. No response rate was indicated.
3. Controls were normal subjects with nonneurological diseases matched on age,
ethnicity, and sex. ;
1. 77 cases (57 males, 20 females, mean
age=59±8 years) from 89 consecutive patients
recruited from a clinic during the period 19791987.
2. Controls (80) were in-patients with various
types of neurological diseases , and were
matched to cases by age, sex, life-style
(alcohol drinking, smoking), education, origin,
and cultural background over same period
1. Cases were diagnosed by neurologists from
1978 to 1979.
2. Of the 145 patients who received the study
questionnaires, 105 replies were obtained.
3.Cases included 6 fALS patients.
4. Controls were not described.
1. All individuals included in the Swedish
census in 1980 who were economically active
in
1. 66 cases and 66 controls.
2. 31 females.
3. There were more married ALS cases
(45) than controls (30).
4. A lower level of education was seen
among ALS cases (22/66 cases with
high school or less education), as
compared to controls (3/63).
3. Lead and mercury(unexposed/exposed): cases=51/29,
controls=77/11 OR=3.98(3.20-4.76) p=0.001.
Exposure to lead:
1. Occupational and residential exposure information was
obtained via a mail-in questionnaire. Binary variables for
specific risk factors (including lead) were created based job
titles.
2. The most frequent metal exposures were welding fumes (11/8
cases/controls), lead ( 9/6), nickel (3/5), mercury (4/2), and
chromates (1/3).
14
1. Cases, 77; 43, males, 34 females, 44
spinal, 32 bulbar. Age=65±9.3 years,
range 42-83years; onset age=62.4 (60.164.7) years, age at diagnosis= 63.7(61.466.1) years.
2. Controls, 185, male, 69, female, 116,
different from cases. Average
age=57.5±13.0 years, with a range of
28-84 years.
Exposure to heavy metals:
1. History of occupational exposure to heavy metals and metal
fumes was identified by interview using a questionnaire based
on standardized criteria in occupational epidemiology.
2. Exposed to metals or metal fumes, spinal + bulbar
controls=7/178, cases=9/68, OR=1.83(0.82-4.14).
3. Exposed to metals or metal fumes, spinal, controls=7/178,
cases=8/36, OR=2.94(1.20-7.21).
7
1. Cases: 125 males, 54 females, mean
age=60 years (SD=10 years).
2. Controls: 125 males, 54 females,,
mean age=61 years (SD=10 years).
141controls were unrelated to patients,
and 38 controls are related ALS patients.
Among related controls, 96 controls
were spouses, 35 controls lived in the
community controls, and 10 were
acquaintances.
No information on race was available. .
Exposure to heavy metals:
1. Occupational exposure to metals was ascertained using a selfreported questionnaire, which included a question specifically
about exposure to metals.
1. Both sexes combined (exposed/unexposed): cases=55/123,
controls=43/136, OR=1.41(0.89-2.25).
2. Men (exposed/unexposed): cases=51/74, controls=41/84,
OR=1.41(0.86-2.36).
3. Women (exposed/unexposed): cases=4/49, controls=2/52,
OR=2.12(0.43-10.45).
Exposure to heavy metals and hard labor:
Information on occupational exposure to heavy metals was
collected using a questionnaire administered via personal
interview, including a question about continuous contact with
specific metals within 5 years prior to disease onset.
1. Participated in hard labour: cases=54, controls=39, RR=2.4,
Chi-square=6.4, P<0.05.
2. Exposed to heavy metal: cases= 7, controls=4, RR=1.8; Chisquare=1.0.
Exposure to heavy metals:
1. Information of exposure to metals was obtained via a mail-in
questionnaire, with a question on an employment history.
2. Of the 105 ALS cases, 26 reported exposure to one or more
heavy metals; 8 of 164 were exposed.
10
1. The average age at onset was 55.6
years, ranging from 19 to 83 years.
2. There were 47 women and 58 men.
1. The age range at the start of follow-up
was 16 to 98 years, with a median of 43
years.
3
Exposure to heavy metals:
1. Occupational information was identified from the 1970 and
1980 censuses; welding was considered to be an occupation
6
5
N/A
(14)
Gunnarsson,
1992,
Sweden
(15)
Casecontrol
Malek,
2013, USA
(16)
Casecontrol
Park, 2005,
USA
(17)
Cohort
Study
1970 or in 1980, and who were alive on
January 1, 1981, for a total of 4,812,646
subjects (2,649,300 men and 2,163,346
women). Subjects were followed from January
1, 1981 until
December 31 1995 or until death, whichever
came first.
1. Cases 45-79 years of age were frequency
matched to a random sample of 500 population
controls within the same age range.
2. A total of 112 patients diagnosed with MND
in the age range 45-79 was identified in the
study area, which included 1-2 million
inhabitants.
3. The response rate in different counties
ranged from 61-81% for controls, and from 74100% for cases.
1. SALS patients were recruited from 3 major
neurology clinics, (2 in Pittsburgh and 1 in
Philadelphia), , between December 2008 and
July 2010.
2. Patients were diagnosed using EI Escorial.
3. fALS cases and ALS cases with other
neurological conditions present were excluded.
4. Cases and controls were required to speak
English. Controls were selected from the
corresponding geographic region (Western
Pennsylvania or the Greater Philadelphia area)
and matched to cases on a 1:1 basis by age of
onset/first ALS symptoms (±5 years), sex, and
race.
5. Of the 106 patients contacted, 78
participated, for a response rate of 73.6%;
however, only 66 cases were included in the
analysis due to lack of corresponding controls.
1. Death certificate information for all deaths
from 22 participating states in the years 1992–
1998 was obtained using the National
Occupational Mortality Surveillance System,
providing underlying and contributing causes
of death. 2. Controls were all decedents with
no mention of neurologic disease, degenerative
or otherwise, and excluding: accidental causes,
malignant neoplasms of the brain (ICD 191),
other senile and presenile organic psychotic
conditions (ICD 290), diseases of the nervous
2. The number of male ALS cases was
1,411 with an average age of 70 years;
the number of females cases was 554
with average age of 69 years.
involving exposure to heavy metals.
2. Among welders, there were 24 cases, with an estimated
RR=1.6 (1.1–2.4).
1. Completed questionnaires were
received from 92 MND cases (58 men
and 34 women) and 372 controls (189
men and 183 women), corresponding to
a response rate of 85% among the cases
(men 83% and women 89%) and 75%
among the controls (men 74% and
woman 75%).
2. Among the controls, the proportion of
respondents was proportionately lower
than among those working in agriculture
or forestry (63%), but among the cases,
this proportion was equal to other
occupations.
The majority of cases and controls were
male (68.2%), Caucasian/White (98.5%)
and from Western Pennsylvania
(86.4%). Cases (mean ± SD: 57.1 ± 13.2
years) were slightly older than controls
(56.4 ± 13.5 years), although this
difference did not achieve statistical
significance (p = 0.07).
Exposure to heavy metals:
1. Occupational information was obtained by mail-in
questionnaire using welding as a proxy for lead exposure to lead
vapour.
2. The ORs for lead and welding were 2.8(0.7-9.2) and 3.7 (1.113.0), respectively.
N/A
Exposure to heavy metals:
1. Exposure information in for occupations held for at least two
years after 19 years of age was obtained by personal interview,
according to the 1980 US Census industrial and occupational
classification system.
2. Regarding heavy metals, there were 19/66 cases/controls
exposure, leading to an OR=0.89 (0.84-4.24).
2. After controlling for smoking (ever vs. never) and education
(high school or less vs. more than high school), cases reported
significantly greater occupational exposure to metals (OR =3.65;
95% CI: 1.15, 11.60) and pesticides (OR = 6.50; 95%
CI: 1.78, 23.77) than controls.
3. Occupational exposure to electrical or electronic equipment,
machinery or electromagnetic fields again appeared to be
protective against ALS (OR =0.28; 95% CI: 0.11, 0.69).
4. Additional individual risk factors were also considered, but
the data was not shown because the sample size was too small.
N/A
The number of decedent participants is
given below.
Exposure to heavy metals:
1. Information on occupational exposure to heavy metals was
obtained from the National Occupational Mortality Surveillance
System. Occupations were specified as mutually exclusive
subsets of Bureau of the Census occupation codes.
2. There were 44,545 deaths in welding occupations, including
70 ALS cases.
3. The standardized mortality ratio was 0.66 (0.49-0.88) for
age >65 years; 0.89(0.53-1.47) for age <-65 years, adjusted for
age, race, gender, region and socioeconomic status.
N/A
Group
White men
White
women
Non-white
men
Deaths
due to
ALS
3,851
2,152
203
4
Total
deaths
1,479,921
803,110
203,862
Qureshi,
2006, USA
(18)
Case
control
system and sense organs (ICD 320–389), and
neoplasms of the lymphatic and hematopoietic
tissues (ICD 200–208), due to suspect
associations with solvents or electromagnetic
fields (EMFs).
1. 95 subjects with ALS and 106 healthy
control subjects between April 1998 and
August 2002.
2. Cases were identified from clinic. Controls
were non-blood relatives (spouses), friends, or
unrelated subjects.
3. At recruitment controls were matched to the
ALS subjects by gender and age.
Non-white
women
Total
Fang ,
2010, USA,
(20)
Casecontrol
Casecontrol
1. All study participants (cases and controls)
were recruited between 1993 and 1996.
2. ALS cases were recruited from two major
referral centers in New England.
3. Cases were required to live in New England
for at least 50% of the year, to be mentally
competent, and to speak English. 71% of
eligible cases participated in the study (n =
111). About 85% of the cases were enrolled
within 1 year of diagnosis and the remainder
within 2 years.
4. Population controls were identified through
random telephone screening, had no
neurological disease, and were sex, age (30–
55, 56–65, and 66–80 years) and region
matched to cases. 354 eligible controls were
contacted, 270 (76%) were enrolled, 256
completed the entire questionnaire.
1. Included a subset of registry cases
comprising MND cases who donated blood
between January 23, 2007 and September 30,
2007; 208 cases were eligible, of whom 200
were enrolled, including 163 ALS cases
(including 12 possible cases), 30 progressive
muscular atrophy cases, and 7 primary lateral
sclerosis cases. [Note: most studies only use
definite and probable cases.]
2. Between May 2007 and May 2008,
contacted 359 controls already enrolled in this
study for additional informed consent and
blood sample collection. A total of 252
controls consented to participate in this study,
of which 229 ultimately donated a blood
sample.
127,453
6,347
2,614,346
Characteristics of the study subjects are
summarized below.
Group
Male
Caucasian
Mean age
Year± SD
Fang, 2009,
USA
(19)
141
Cases
60
(63.2%)
91
(95.8%)
54.4
±13.1
Controls
58
(54.7%)
102
(96.2%)
52.5
±14.9
1. The median age at diagnosis for cases
was 60 years (range 30–79 years) and
the median age 2 years before interview
for controls was 59 (29–78)years.
Diagnosis was made an average of 14.3
months after the onset of symptoms.
2. Males: cases, 66 (60.6%); controls,
156 (61.7%). Females: cases, 43
(39.4%); controls, 97 (38.3%)
3. 27 (25%) of the cases had bulbar
onset and 82 (75%) had trunk or limb
onset.
Exposure to lead-heavy metals:
1. Each ALS and control subject completed a comprehensive
risk factor questionnaire at enrolment. Subjects answered
questions about risk factors
for ALS, disease presentation (ALS subjects only), and family
and medication histories.
2. Of the 95 subjects in the ALS group, the exposure most
commonly reported was exposure to pesticides (n=18), followed
by lead (15), industrial solvents (5), mercury (5) and
miscellaneous agents (number is not specified). .
N/A
Exposure to lead:
As in Kamel et al. (2006) above, occupational history
information was obtained via interview. Duration of
occupational exposure to lead was categorized into four levels
(0, 1–399,400–1,999, and 2,000 days of exposure). The number
of cases and controls exposed to lead at least 10 times and
accumulated for one day is summarized below.
N/A
Group
Overall
Smokers
Non-smokers
Cases
55
33
22
Controls
35
25
10
OR
1.9(1.1-3.4)
1.9(0.9-3.8)
2.8(1.0-7.8)
Cases (exposed/unexposed)= 35/84,
Controls(exposed/unexposed)=55/201.
1. Participants were recruited from
2003–2007.
2. 184 cases and 194 controls among US
veterans; most are male (98% of cases,
and 94% of controls) and white (94% of
cases, and 98% of controls).
5
Exposure to lead:
Lead concentrations in blood samples were determined by
inductively coupled plasma mass spectrometry.
1. After adjustment for age, a unit increment of log2-transformed
lead (equivalent to a doubling of blood lead) was associated with
a 2.6-fold higher odds of ALS (95% confidence interval: 1.9,
3.7). Adjustment for smoking (ever/never) in addition to age did
not materially change the results.
2.A dose response for the lead-ALS association was also seen
when blood lead was categorized in tertiles; after adjustment for
age and type 1 collagen, the odds ratio for the highest compared
with the lowest tertile was 2.1 (95% confidence interval: 1.1,
3.8; P for trend= 0.008).
N/A
Kamel,
2005, USA
(21)
Casecontrol
3. Response rate: cases, 200/208; controls,
229/252.
1. All study participants (cases and controls)
were recruited between 1993 and 1996.
2. ALS cases were recruited from two major
referral centers in New England.
3. Cases were required to live in New England
for at least 50% of the year, to be mentally
competent, and to speak English. 71% of
eligible cases participated in the study (n =
111). About 85% of the cases were enrolled
within 1 year after diagnosis and the remainder
within 2 years.
4. Population controls were identified through
random telephone screening, no neurological
disease, sex, age (30–55, 56–65, and 66–80
years) and region matched. 354 eligible
controls were contacted, 270 (76%) were
enrolled, 256 completed the entire
questionnaire.
1. The median age at diagnosis for cases
was 60 years (range 30–79 years; the
median age at 2 years before interview
for controls was 59 years (range 29–78
years). Diagnosis was made 14.3 months
after the onset of symptoms on average.
2. Males: cases, 66 (60.6%); controls,
156 (61.7%). Females: cases, 43
(39.4%); controls, 97 (38.3%)
3. 27 (25%) of the cases had bulbar
onset and 82 (75%) had trunk or limb
onset.
Exposure to lead
1. Ever exposure to lead (unexposed/exposed): cases=67/35,
controls= 193/53; OR=1.9(1.4-2.6).
2. Gradient in lead exposure across tertiles (number, p
trend=0.02):
Days exposed
to lead
No. of
ALS
cases
N/A
No. of
control
s
OR
0
67
193
1
1-399
8
17
1.6 (0.6-3.9)
400-1999
11
17
1.9 (0.8-4.3)
2000+
16
20
2.3 (1.1-4.9)
3.Blood lead levels (µg/dl): cases=5.2±0.3; controls=3.4±0.4
(p<0.05).
References
1. Armon C, Kurland LT, Daube JR, et al. Epidemiologic correlates of sporadic amyotrophic lateral sclerosis. Neurology. 1991;41(7):1077-84. 2. Campbell AM, Williams ER, Barltrop D. Motor
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