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Amyotrophic lateral sclerosis among chamorro migrants from guam.

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Amyotrophc Lateral Sclerosis
among Chamorro Migrants from Guam
Ralph M. Garruto, PhD, D. Carleton Gajdusek, MD, and Kwang-Ming Chen, M D
Amyotrophic lateral sclerosis (ALS), which occurs in unusually high incidence among the Chamorro people on the
island of Guam, has developed in 28 Chamorro migrants-24 of whom had onset in the United States, Japan,
Germany, or Korea-after periods of absence from Guam of 1 to 34 years. Thus, the latency period for the disease, if
caused by environmental factors on Guam, may be over three decades. Four further patients developed ALS within
1 to 14 years of their return to Guam after long-term residence in the continental United States. The minimum
exposure time to environmental variables on Guam, based on age at migration, was 18 years, and all patients had
spent their childhood and adolescence on Guam. Estimates of crude mortality rates for ALS from these data are
considerably higher than for the United States population, and lower than the ALS mortality rates for nonmigrant
r
Chamorros on Guam.
Garruto RM, Gajdusek DC, Chen K-M: Amyotrophic lateral sclerosis among Chamorro migrants from
Guam. Ann Neurol 8:612-619, 1980
Since the turn of the century, amyotrophic lateral
sclerosis (ALS) has been known to occur in unusually
high incidence among the Chamorro people of Guam
[ l , 2 , 12, 131. Its occurrence in migrants to the
United States and elsewhere, who have been away
from Guam for long periods, has important implications concerning the possible cause of the disease.
We find that ALS has occurred in at least 28 migrants
from the high-incidence Chamorro population of
Guam; 10 of these patients were autopsied and had
neuropathological confirmation of ALS.
Two previously published surveys had located 9 cases
of ALS among Chamorro migrants to the US mainland [6, 171. O u r survey among Chamorro people
who have migrated from Guam identified an additional 19 cases of clinically classic disease with onset
1 to 34 years after their departure. The search for
cases of ALS in Chamorro migrants has included extensive inquiry within Guamanian communities in
the United States, a search of military records, and
inquiry among migrants’ relatives still living on
Guam. O n Guam, such inquiry was coordinated by
our National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) Research Center with its contacts throughout the island.
This survey of Guamanian ALS in Chamorro migrants provides data on the length of exposure to the
Guamanian environment before migration and the
subsequent period of absence from Guam prior t o
onset of ALS. Such data influence our thinking on
whether toxic, deficiency, or infectious agents on
Guam, with or without genetic interaction, are a
cause of this disease. Epidemiological and demographic characteristics of all 28 cases of ALS, as well as
case histories for the 19 new patients located during
the recent survey, are presented (the other 9 case
histories have been recorded previously [6, 191).
Parkinsonism-dementia (PD), which is associated
with the high incidence of ALS on Guam, has also
been clinically and neuropathologically observed
among Chamorro migrants, but with certain atypical
features [3a, 4 , 61. In our current survey we have
identified several additional cases of PD, including
1 with confirmatory neuropathology. However, the
clinical diagnosis of P D is fraught with problems of
differential diagnosis, and several cases are currently
being followed. Therefore, we are limiting our observations in this paper to ALS.
From the Laboratory of Central Nervous System Studies, National
Institute of Neurological and Communicative Disorders and
Stroke, National Institutes of Health, Bethesda, MD, and the
NINCDS Research Center, Tamuning, Guam.
Received Mar 7, 1980, and in revised form May 15. Accepted for
publication May 17, 1980.
612
History of Chamorro Migration from G u a m
Guam was under Spanish occupation for 300 years
prior to 1898, when the United States gained control.
From 1898 to 1950, strict military control of the
island, geographic isolation, unavailability of civilian
transportation, and noncitizen status of the population limited the opportunity to emigrate either to the
United States mainland or to the other Pacific islands.
During World War 11, however, many Guamanians
joined the US military forces, particularly the Navy
Address reprint requests
Ralph M, G
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Room 5B25, National Institutes of Health, Bethesda, MD 20205.
0364-5134/80/120612-08$01.25 @ 1980 b y Ralph M. Garruto
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and Marines, and left the island. With congressional
passage of the Organic Act in 1950, US citizenship
and a civilian government were granted to Guamanians, thus facilitating their travel outside the island.
After World War 11, increasing numbers of Guamanians continued to enter the US military services, and
many veterans later settled in Hawaii and the continental United States.
By 1957, at least 80% of the Guamanian migrants
interviewed in California had resided there for less
than 10 years, with an average of 7.4 years [19].
Twelve percent had been living there between 15
and 25 years and 2% for more than 25 years. Fortythree percent of the migrants were under age 35.
It is impossible to obtain close estimates of the size
of the migrant population, particularly during the
past 20 years, when the most extensive emigration
occurred. However, rough estimates place the migrant population at about 5,000 in the 1950s, 10,000
in the 1960s, and over 20,000 in the 1970s. According to the 1970 US census, the total Chamorro
population residing on Guam was approximately
47,000, so that about one-third of all Chamorros
now live in Hawaii and the continental United States.
The major areas of Chamorro settlement are Hawaii,
the West Coast, and Washington, DC. There are
particularly heavy settlements in San Diego, Los
Angeles, Long Beach, the San Francisco Bay area,
and Seattle.
Case Material a nd Ascertainment
During the past three decades of intensive study of ALS
and P D on Guam by the staff of the N I N C D S Research
Center, there has been a keen awareness of the importance
of these disorders occurring in migrants from Guam. All
accounts of ALS in migrants have been pursued in the following ways: (1) from relatives of patients on Guam, (2)
from patients who have returned to Guam with their disease, (3) on referral from interested neurologists and other
physicians in the United States, ( 4 ) through surveys of
Guamanian households by interview and direct contact, (5)
with the aid of local stateside Guamanian organizations, (6)
by a search of US military records, and (7) by a review of all
California death certificates for the 19-year period 1955 to
1974 [14, 151. In 1977, Judith Farquhar conducted a search
for chronic disease among Guamanian migrants in California. This study uncovered several cases of ALS and suspected ALS in addition to those previously verified by earlier surveys [6, 193.
The 28 ALS patients (21 of whom had disease onset in
the United States, 3 in other countries, and 4 after returning to Guam from long-term residence o n the US mainland) all had an anamnesis strongly indicative of motor neuron disease, or lytico, as the Chamorros call this familiar
illness. Of these, 24 were given a clinical diagnosis of ALS
by neurologists and other physicians. Fifteen of the patients
were examined by a neurologist from our N I N C D S research team, and the 10 autopsied cases all had confirma-
tory neuropathological changes. Only 4 of the 28 ALS patients had never been examined by a physician but were
identified through detailed accounts from their relatives who are very familiar with lytico. With the aim of
having the migrant patients examined by members of our
own team, interviews were conducted with many of the patients and their close family members. Many of the patients
had returned to Guam after the onset of their disease and
were examined neurologically on a regular basis along with
all other ALS patients on Guam.
Skeptical physicians might legitimately question the
diagnosis of cases not studied neuropathologically. However the validity of our clinical diagnosis has been confirmed neuropathologically in over 95% of the several
hundred cases studied on Guam. Differential diagnosis of
ALS is not a serious problem because of the characteristic
symptoms, progressive nature, and regular course of the
disease. Furthermore, by the late stages of the disease, lay
diagnoses by Guamanians have been substantiated in all but
a very few of the cases that have eventually been brought to
our attention.
Case Summaries
Clinical summaries of the 19 new ALS patients among the
28 with onset of their disease outside Guam, or in longterm migrants who returned to Guam prior to onset, are
reported in the Appendix. Summaries for the remaining 9
patients were published previously-7 cases were reported
by Torres et al in 1957 1191and 2 by Eldridge et a1 in 1969
[6]. Overall, the mode of onset, the progression of upper
and lower motor neuron involvement, and the duration of
disease d o not differ from the nonmigrant Chamorro cases
on Guam.
Epidemiological Findings and Discussion
Epidemiological and clinical data on the 28
Chamorro patients in whom ALS developed after
long-term absences from Guam are presented in the
Table; this table includes the 9 patients from previous surveys [6, 191, who are identified by their designations in these earlier reports. The minimum period
of residence on Guam for all these patients was from
birth to age 18. The longest period of absence from
Guam before onset of ALS was over three decades.
Since only rough estimates are available of the total
number of Guamanians in the United States at any
one time, it is impossible to make an accurate calculation of mortality or incidence figures for ALS
among stateside Guamanians. Additionally, the age
distribution of this population is known only approximately. However, one can estimate the order of
magnitude of the crude mortality. Twenty-one of the
28 migrant patients have died since 1960. With migrants from Guam estimated at about 10,000 in 1960
and just under 30,000 in 1980, we can use 20,000 as
a rough population mean for this 20-year period.
This gives an average annual crude mortality rate of 5
cases per 100,000 per year. Five of the migrant pa-
Garruto et al: ALS in Chamorro Migrants
613
Epidmziological Summary of 28 Pdtients with ALS among Chdmorro Migrants from Guam
Case
NO.^
NINCDS
Patient No.
and Earlier
Citation
9228
JAG
9445
JSF
57-3; 69-1
57-4; 69-2
JRM
9368
57-2; 69-7
9283
1362 (57-6;
69-4)
JPQ
57-5; 69-3
9484
0360
69-9
57-7; 69-5
9194
1863
MSK
905 1
57-1; 69-6
69-8
9152
9360
9216
9341
9374
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
Migration Summary Prior
to Onser
Birth
Sex
Place
Year
Place
M
M
F
M
M
M
M
M
M
M
M
Agana
Agana
Agana
Umatac
Guam
Guam
Agana
Piti
Agana
Umatac
Agana
1910
1920
1931
1915
1859
1859
1914
1928
1918
1936
1921
CA
CA
CA
CA
CA
CA
CA
Korea
CA
CA
NH
M
M
F
M
F
Yona
1909
Guam
1910
Agana
1923
Agana
1916
Guam
1901
Guam
-1901
Barrigada 1941
Merizo
1934
Agana
1901
Umatac
1939
Agana
1913
Guam
1923
Agana
1932
Agana
1935
Agana
1917
Tumon
1925
Agana
1918
F
M
M
F
F
M
M
M
M
M
M
M
Onset
Age
59
48
46
55
-49
-48
54
43
38
35
30
CA
67
CA
37
CA
51
Japan
41
CA
64
CA
-48
CA
24
Germany 23
CA
64
Guam
25
CA
41
CA
42
ME
33
Guam
34
Guam
51
CA
47
57
Guam
Year
Age Year
Left Left
Years
Away
Years
Returned
25
1935
1969
1968
20 1940
21
1952
1977
31 1946
1970
1909 -25 -1885
1908 -25 -1885
1968
32
1946
1971
21 1949
22 1940
1956
20 1956
1971
18 1939
1951
34
28
25
24
-24
-23
22
22
16
15
12
0
0
58 1967
31 1941
46 1969
36 1952
61 1962
45 -1946
21 1962
21 1955
63 1964
21 1960
23 1938
21 1944
21 1953
21 1956
33 1950
21 1946
19 1937
9
0
0
0
0
0
0
0
0
0
1976
1947
1974
1957
1965
1949
1965
1957
1965
1964
1954
1965
1965
-
1969
1968
1972
1975
6
5
5
3
3
3
2
1
3
16
9
11
10
12
15
24
0
0
0
0
0
0
0
0
0
1
2
2
3
3
6
11
14
Deathb
Year
62
52
48
61
NA
NA
49
NA
43
33
Yes
1972 Yes
NA
1972 Yes
NA
1979 Yes
NA
1976 Yes
1920s Notseen N A
1920s Not seen N A
NA
1973 Yes
NA
1977 Yes
1950s Norseen N A
NA
1979 Yes
Yes
1954 Yes
Alive
NA
54
44
66
51
33
29
66
29
43
NA
40
NA
56
49
59
1950s
1977
1960
1968
1952
1974
1963
1967
1968
1957
1960s
1972
1970s
1973
1974
1977
59
"Boldface case numbers identify patients previously reported: 57-1 to 57-7 refer respectively toTorres et al, 1957 [19]-Cases
1, Navy man 2, and a middle aged woman in this sequence; 69-1 to 69-9 refer respectively ro Eldridge et al, 1969 [6]-Patients
1035, in [(.I).
"Estimated decade of death based on a mean duration of ALS on Guam of approximately 5 years.
NA
=
Clinically Pathologically
Verified
Confirmed
Age
Yes
NA
Yes
NA
Yes
NA
Yes
Yes
Yes
NA
Notseen N A
Yes
NA
Yes
Yes
Yes
NA
Yes
Yes
Yes
Yes
Yes
NA
Yes
Yes
Yes
NA
Yes
Yes
Yes
Yes
Yes
Yes
1 and 2, two brothers, Navy man
1to 9 inclusive (inTable 3, page
no available information.
tients died in the 14 years 1947 to 1960; during that
period 5,000 migrants may be taken as a reasonable
estimate of the population mean. This gives a yearly
crude mortality rate of 7 per 100,000.
These rates, which are only rough order of magnitude estimates, are at least three times as high as
rates for the continental United States; yet they are
also less than one-third the rate currently observed
on Guam and less than one-quarter of the average
annual crude mortality rate observed on Guam over
the past two decades. Any error in these mortality
rates will surely be in the direction of having missed
instances of ALS through incomplete case ascertainment, and thus the real rates may be somewhat
higher than our estimates. However, it seems improbable that the mortality could be twice as high as
our estimates because our search for cases has been
comprehensive. Thus, the migrants appear to have
less likelihood of developing ALS than d o those
Chamorros who remain on Guam, but their risk of
developing the disease is still considerably increased
over that experienced by the general US population.
Two further cases of motor neuron disease have
been identified in a brother and sister aged 16 and 15
years at the onseg of their disease in California, 7 and
4 years, respectively, after they had left Guam. These
unusual siblings with motor neuron disease have not
been included here; they will be reported in detail at
a later time.
The patients residing in California, who comprised
18 of the 2 1 with onset on the US mainland, were
found to have housing and food consumption comparable to average non-Guamanian families of similar
income status living in the same area. A few traditional Chamorro foods, particularly betel nuts,
achote, taro, and even cycad nuts, were occasionally
obtained as gifts from visiting Guamanians or by mail
from relatives, and these foods were rarely obtained
from localities other than Guam. Some of the migrants had returned to Guam for short visits of several weeks or months, but they had onset of their
ALS in the United States. However, 4 of the patients
had onset on Guam 1,to 14 years after their return
from the mainland (Table).
614 Annals of Neurology Vol 8 No 6 December 1980
who brought new cases to our attention or provided additional
information on existing cases.
The ALS-affected migrants had a mean age at migration of 29.4 years, with a range of 18 to 63 years.
The average number of years away from Guam prior
to onset was 13.6, with a range of 1 to 34 years. The
mean age at onset was 44.8 years (range, 2 3 to 67),
with a mean age at death of 48.8 (range, 29 to 6 6 ) and
a duration of illness of 4.1 years (range, 2 to 9). This
mean age at onset is 4 years less than for Guamanians
with ALS who have never left the island. The duration of illness, however, is similar in both migrants
and nonmigrants. The reason for the earlier onset in
the migrants is not known.
The steady decline in the average annual incidence
of ALS on Guam and the upward shift in the average
age at onset in recent years 14, 5 , 14, 161 suggest that
toxic, infectious, or deficiency factors are likely to be
involved in pathog, 4 s 18, 11, 221. However, it is
difficult to explain how toxic or deficiency factors
would operate to produce onset after absences of
over 30 years from exposure to the Guam environment. ALS in migrants conforms t o a slow virus
model, as in kuru and Creutzfeldt-Jakob disease, but
to date experimental transmission to primates and
other laboratory animals has been unsuccessful [ 8 ] ,as
has the search for a virus by cultivation of brain tissue
in vitro, by inoculation of cell cultures, or by the
attempt t o find a viral protein, antigen or antibody, or
nucleic acid in tissues of the patients [lo, 18, 20,
211. Recent genetic studies (published and unpublished) involve research on HLA markers, red cell
enzymes, blood group genetics, serum proteins,
dermatoglyphics, family studies, and a pedigree
analysis of Umatac Village back to 1840; these
studies have not demonstrated any clear pattern of
differential genetic susceptibility to the disease 13, 9,
13a, 171.
It is of critical importance that there be continued
neuroepidemiological monitoring of the Guamanian
migrant population in the United States, particularly
of the second-generation offspring, most of whom
still require another 20 years to reach the age at risk.
Continued epidemiological surveillance of the now
long-term Filipino migrant population on Guam and
the relatively new but steadily increasing number of
Korean immigrants to Guam is equally important [7].
Judith Farquhar kindly provided information on patients whom
she located with the help of Maria Perez and the Sons and
Daughters of Guam Club of San Diego, and with the partial support of the Asian American Mental Health Research Center. Dr
Chris C. Plaro of the National Institute on Aging assisted in obtaining the migration data while on Guam in 1977. Dr Clarence J.
Gibbs shared the scientific direction of the studies on Guam with
one of us (D. C. G.) over the past decade and continued his advice
and assistance throughout this study. We also thank Dr Olivia
Crue, Jose M. Torres, Mary E. Hernandez, Manuel C. Cruz, Francisco C. Leon Guerrero, and Luis Munot of the NINCDS Guam
Research Center staff as well as the many cooperating physicians
Appendix: Clinical Summaries
Case 1 (NINCDS No. 9228)
This Chamorro male ALS patient was born in Agana, Guam,
in 1910. At age 25 he emigrated to San Francisco to study,
and he remained there as a mechanical engineer for the
next 34 years. In April, 1969, at the age of 59, he noted
muscle twitches and weakness in his right arm and hand. In
August he was seen by D r F. Norris of the Pacific Medical
Center, San Francisco. A myelogram and muscle and renal
biopsies were performed, and a diagnosis of ALS was made.
Weakness, fasciculation, and atrophy had spread to his
right leg and left side by the end of t h e year. H e was first
examined at the NINCDS Research Center in July, 197 1,
2 months after his return to Guam. H e presented a fullblown picture of ALS with bulbar and pseudobulbar signs,
marked atrophy and weakness of the neck and upper limb
muscles, spastic weakness and hyperreflexias of the legs,
and footdrop. Fasciculations were prominent over the
shoulder girdle. Unsustained ankle and patellar clonus
were observed, and plantar responses were extensor bilaterally. The sensory system was intact.
His disease progressed rapidly, and 4 months later he
was confined to a wheelchair and unable to perform useful
movements of his limbs. Speech was barely intelligible. In
January, 1972, 33 months after onset of his ALS, he fell at
home and sustained a skull fracture over the right
parietooccipital region. He died four days later. Autopsy
revealed a large three-day-old subdural hematoma in addition to a typical pathological picture of ALS.
Case 2 (JAG)
This Chamorro man was born in Agana, Guam, in 1920.
H e joined the US Navy in 1940 and shortly thereafter left
the island. Between 1048 and 1950 he returned to Guam
frequently for short, service-related visits of one to three
days each. In 1968, while stationed in California, he developed pain in his right shoulder and within a year retired
from the service. H e died at the San Diego Naval Hospital
in December, 1972, at the age of 52 years with a diagnosis
of ALS. H e had developed the disease 28 years after his
original departure from Guam.
Case 3 (NINCDS No. 9445)
~
This Chamorro woman was born in Agana, Guam,
in 1931. In 1952, at age 21, she migrated to the midwestern United States and eventually settled in the San
Francisco Bay area in 1966. Early in 1977 she noticed
weakness of her right shoulder and hand and difficulty with
speech. Several months later she began to walk clumsily
and noted fasciculations of the right arm muscles and slowness in swallowing. D r C. M. Poser of the University of
Vermont diagnosed early ALS.
In December, 1977, she returned to Guam and was seen
at the NINCDS Research Center. She presented with
moderate atrophy, marked fasciculations of the tongue, and
slurred speech. There was mild weakness of the shoulder
girdle and neck muscles. Prominent atrophy was noted in
the small hand muscles and forearm, especially on the right
Garruto et al: ALS in Chamorro Migrants
615
side. H e r gait was normal. Deep tendon reflexes were
slightly hyperactive, but plantar responses were flexor
bilaterally. Sensation was intact. In January, 1978, she was
still ambulatory, but her speech was almost unintelligible.
She had difficulty manipulating food in her mouth, and
swallowing was very slow. Respiration was mostly diaphragmatic. Weakness was detected in neck flexor and extensor muscles. The shoulder girdle was mildly weak, and
the marked atrophy of her intrinsic hand muscles remained
unchanged. Hip girdle muscles were normal, but there was
minimal flattening of the anterior tibialis bilaterally. Fasciculations and upper motor neuron signs were not seen.
She returned to San Francisco and died there in June,
1979, at the age of 48. An autopsy was not performed.
Case 4 (JSF)
This Chamorro man was born in Umatac, Guam, in 1915.
In 1946, at the age of 31, he emigrated to the US mainland.
In 1970 he noticed weakness in his arms and hands. Within
a short time he began to drag his feet. His ALS progressed over the next several years until he could no longer
lift his arms or walk, and he became wheelchair-bound.
Muscle stiffness and tremors were not observed. H e had
increasing difficulty with speech and drooled. No signs of
dementia were observed. In 1976, at the age of 61, he died
in Palo Alto, CA, after a 6-year course.
Case 7 IJRM)
This Chamorro man was horn in Agana, Guam, in 1914. At
the age of 32 he joined the “insular force” and remained o n
Guam during the war. In 1946 he joined the US Navy and
left the island. Shortly before the onset of his disease in
1969 he was working as a stockman at an Air Force base in
California, having already retired from the Navy. At work,
a box fell on his shoulder, and he associated the onset of his
disease with this incident. By 1971 he had become dysarthric. He died in January, 1973, at the US Air Force Hospital in Los Angeles at the age of 59 with a diagnosis of
ALS.
Case 8 (NlNCDS No. 9368)
This Chamorro man was born in Piti, Guam, in 1928. In
1949, at age 2 1, he moved to Hawaii, later joining the US
Army in San Francisco in 1950. Between 1950 and 1974 he
travelled widely throughout Korea, the Panama Canal
Zone, the US mainland, Germany, and Vietnam.
At the age of 43, while in Korea, he noticed difficulty in
buttoning his shirt due to weakness of the right thumb.
Two years later, in November, 1973, he was advised at an
Army hospital in California that he had possible motor
neuron disease, and he was medically discharged from the
Army in 1974 with a diagnosis of ALS.
He returned to Guam the following year and was initially
examined by the N I N C D S Research Center in July, 1975,
at age 4 7 , 4 years after onset. Speech and swallowing were
normal, but his tongue showed prominent fasciculation.
His neck flexors, right deltoid, and triceps muscles were
mildly weak. Moderate muscle atrophy was observed in the
right hand and forearm with no weakness noted on the left
side. Deep tendon reflexes were only slightly hyperactive
at both knees, and plantar responses were flexor. When last
examined in May, 1377, he showed further progression of
lower motor neuron involvement in all extremities without
spasticity. H e returned to the US mainland, where he died
in October, 1077, at the age of 49.
Case 10 (NINCDS No. 9283)
This Chamorro man was born in Umatac, Guam, in 1936.
In 1956, at age 20, he joined the US Navy and left Guam.
H e travelled to various US ports, Europe, and the Far East
until 1971, when he returned to Guam on leave. In late
197 1 he began to notice fasciculations of his shoulders and
tremulousness of the hands whenever heavy lifting was attempted; before long, wasting of the hand muscles developed. H e was officially discharged from the Navy in April,
1972, with ALS. His first examination at the N I N C D S Research Center in May of that y e a r revealed intermittent fasciculations of the deltoid, biceps, and forearm muscles on
the left side, moderate atrophy of the intrinsic hand muscles on both sides, hyperactive jaw jerk, mild pseudobulbar
dysarthria, hyperactive deep tendon reflexes with ankle
clonus, and extensor plantar responses. By May, 1975, he
could not walk at all and showed mild weakness of the orbicularis oculi and facial muscles. The tongue was moderately atrophic with fasciculations. A year later he became
wheelchair-bound and his speech was unintelligible. When
last examined in March, 1979, he showed considerable
difficulty in breathing. He took a little soft food. His upper
extremities were flaccid with only mild weakness of the
legs. Marked spasticity with hyperactive deep tendon reflexes was noted in the lower extremities. He died in April,
1979, at the age of 43.
Case 12 IJPQ)
This Chamorro man was born in Yona, Guam, in 1909. He
left Guam for California in 1967 at age 58 and remained
there until the onset of his disease in 1976. He was visited
by Judith Farquhar in 1977 during her search for chronic
disease among Guamanian migrants. At that time he was
already having trouble walking. H e was examined by an
orthopedist in San Diego and was diagnosed as having ALS.
By early 1980 he had progressed to advanced disease,
could not walk, and had difficulty with speech. This patient
is still alive.
Case 14 (NINCDS No. 9484)
This Chamorro woman was born in Agana, Guam, in 1923
and moved to California in 1969 at the age of 46. H e r
father had died of ALS in May, 1948. Early in 1974 she
began to notice weakness and atrophy of her left arm, and
within 6 months she developed bulbar symptoms. Approximately a year after onset she noted weakness in her
legs. In May, 1976, she was admitted to the UCLA Medical
Center because of progressive difficulties with swallowing
and speech. ALS was diagnosed by Dr J. M. Andrews, and a
gastrostomy was performed. She died in May, 1977, in
Long Beach, CA, at the age of 54.
Case I 5 (NINCDS No. 0960)
This Chamorro man was born in Agana, Guam, in I916 and
joined the US Navy in 1937. As a member of the Navy’s
“insular force,” he was stationed on Guam throughout
616 Annals of Neurology Vol 8 No 6 December 1980
World War 11. H e left the island in 1952. While in Japan in
March, 1957, at age 41, he first noticed stiffness of the legs.
Because of increasing weakness in his legs he was admitted to the San Diego University Hospital in June. He visited Guam during October and November, 1957, and
returned there in March, 1958, after receiving a medical
discharge from the Navy. When first examined by the
NINCDS Research Center in August of that year he
showed dysarthria, dysphagia, emotional incontinence, jaw
and ankle clonus, and hyperreflexia without flexor plantar
response. There was diffuse muscular atrophy with fasciculations, and he was unable to walk without assistance.
The sensory examination was normal, and his mental status
was clear. H e died in May, 1960, at the age of 44 at the
Guam Naval Hospital. Autopsy showed moderate frontotemporal lobe atrophy. Microscopically, in addition to
morphological evidence of ALS in the cord, neurofibrillary
tangles were found in the usual distribution seen in PD.
Case 18 (NINCDS No. 91 94)
This Chamorro man was born in 1941 in Barrigada,
Guam. H e joined the US Air Force in 1962 and was
transferred to the US mainland, where he remained until
1968. In October, 1965, he developed weakness of the left
foot. Three years later he was admitted to the Veterans
Administration Hospital in Monterey, CA, with generalized fasciculations and mild weakness of the right leg
and arms. An electromyogram (EMG) showed widespread
denervation potentials. H e returned to Guam in 1969 and
was examined by the NINCDS Research Center in
January, 1970. He showed flaccid weakness of all extremities and could walk only short distances with crutches.
N o bulbar palsy was demonstrated. H e was last examined
on Guam in July, 1973. At that time he showed obesity,
with increasing dyspnea, weakness of the upper extremities, complete flaccid paralysis of the legs, absent
deep tendon reflexes, and normal swallowing and speech.
H e died of respiratory complications in January, 1974, at
the age of 33.
Case 19 (NZNCDS No. 1863)
This Chamorro man was born in Merizo, Guam, in 1934,
and in 1954 enlisted in the US Army. H e served 2 years
overseas. Late in 1957, at age 23, he developed cramps and
weakness of the right hand. The weakness spread to his left
side, and he began to show dysarthria. H e returned to
Guam in 1958. In October, 1959, he was first seen at the
NINCDS Research Center by Dr Asao Hirano, who
confirmed a diagnosis of ALS with upper and lower motor
neuron involvement of the brainstem and cervical cord. In
October, 1961, the US Naval Hospital neurologist on
Guam reported more advanced dysarthria and dysphagia,
cranial nerve weakness, extensive atrophy with fasciculations of the shoulder girdle, and spasticity of the lower extremities. H e died in April, 1963, at age 29, with a total
course lasting 5 years. Postmortem neuropathological
findings confirmed his ALS. This is the youngest patient in
the entire NINCDS series of Guamanian ALS cases.
Case 20 (MSK)
This Chamorro woman was born in Agana, Guam, in 1901
and left for the US mainland in 1964. One year later she
developed weakness and numbness in her palms. In 1966,
at the age of 65, she was still ambulatory but her speech was
dysarthric and she had dysphagia, tongue fasciculations,
and wasting of the interrosseous muscles of the hand as
well as weakness in both arms. Her sensory status and
mental condition were normal. She died 1 year later at
Memorial Hospital in Modesto, CA, with a diagnosis of
ALS.
Case 21 (NINCDS No. 9051)
This Chamorro woman was born in Umatac, Guam, in
1939. She remained in Umatac until 1960, when she married an Air Force sergeant and left the island for New
Hampshire. In 1963 she returned to Guam when her husband was reassigned, and they lived in Anderson Air Force
Base housing. In November, 1964, at age 25, she developed cramps, weakness of the left hand, and slurred
speech. She was initially examined at the NINCDS Research Center in April, 1965. Neurological examination
revealed moderate tongue atrophy with fasciculations,
marked atrophy in both hands and shoulder girdle, flaccid
weakness of the left foot, and prominent fasciculations.
Deep tendon reflexes were hyperactive with an extensor
plantar response on the right. By early 1967 she became
wheelchair-bound. She died after aspiration of food in
October, 1968, at the age of 29. The patient’s mother had
died of PD in 1960. Postmortem examination confirmed
her ALS.
Case 24 (NINCDS No. 9152)
This Chamorro man was born in Agana, Guam, in 1932 and
lived there until joining the US Air Force in 1953. Soon
thereafter he left for Georgia and then Alaska, where he
remained until January, 1960. He returned to Guam for
2% years but reenlisted in the Air Force in July, 1962. H e
was then transferred to Maine, where he lived for the
next 5 years. In November, 1965, at age 33, he developed
fasciculations, weakness, and atrophy of the arms. Several
months later he noted slurred speech, difficulty in swallowing, and stiffness of the legs. In October, 1966, ALS
was diagnosed at St. Albans Naval Hospital in New York.
H e returned to Guam in September, 1967. Examination at
the NINCDS Research Center gevealed psuedobulbar
forced laughter, facial weakness, acrophy of the tongue and
palate, flaccid “hanging arm syndrome,” spastic weakness of
the lower extremities, ankle clonus, and extensor plantar
responses. H e died in June, 1972, at the age of 40. Pathological findings confirmed Guamanian ALS.
Case 25 (NINCDS No. 9360)
This Chamorro man was born in Agana, Guam, in 1935. At
age 21 he joined the US Navy and moved to San Diego.
H e travelled to Hawaii, San Francisco, Washington, DC,
Maryland, and Japan between 1956 and 1966, after which
he returned to Guam. In August, 1969, he developed
weakness of the left hand and twitching of the forearm
muscles. In May, 1970, his condition was diagnosed as ALS
at the Guam Naval Hospital. When examined at the
NINCDS Research Center in February, 1075, he presented mild to moderate weakness and atrophy of both
arms and mild weakness of the left leg. N o fasciculation
was noted, but marked spasticity was seen in both legs and
Garruto et al: ALS in Chamorro Migrants
617
in the left arm. The tongue showed prominent fasciculation
without atrophy. Babinski and Hoffmann reflexes were
present. The sensory system and sphincter muscles were
unimpaired. He returned to the US mainland in 1976 and
was later admitted to the Bethesda Naval Hospital. He was
discharged with advanced ALS and died in the late 1970s.
food. Immunological studies showed a marked increase in
IgG and IgA, a decrease in IgM, and poor rosette formation in lymphocyte cultures. In April, 1977, at the age of 59
he developed aspiration pneumonia and died. Postmortem
examination confirmed Guamanian ALS.
Case 26 (NINCDS No. 921 6 )
References
This Chamorro man was born in Agana, Guam, in 1917.
He joined the US Navy in 1949 and left for California in
1950. He left the service because of diabetes and returned
to Guam in 1962. In June, 1968, he developed weakness of
the left fingers. He was admitted to the Guam Naval Hospital in January, 1969, and was diagnosed as having ALS.
Late in 1970 he developed flaccid leg weakness and dysarthria. Deep tendon reflexes were decreased and plantar responses remained flexor. Weakness, muscle atrophy, and
fasciculations progressively spread to both arms and the
shoulder girdle in 1973, and by April of that year he became restricted to a wheelchair. His tongue was very
atrophic with prominent fasciculations. Deep tendon reflexes were mildly increased in the lower extremities. He
died in December, 1973, at age 56. Postmortem examination confirmed Guamanian ALS.
Case 27 (NINCDS No. 9341)
This Chamorro man was born in Tumon, Guam, in 1925
and joined the US Merchant Marine in 1946. He travelled
extensively to the Near East and Far East until 1950. In
195 1 he joined the US Army and was stationed in Hawaii,
Germany, England, and the Eastern United'States for 6
years. From 1957 to 1967 he was stationed on Guam with
the Navy. He then rejoined the Merchant Marine from
1967 to 1972, visiting various US ports. In 1972 he developed a spastic gait and in May, 1973, was admitted to the La
Jolla Veterans Administration Hospital, where ALS was
diagnosed. He returned to Guam in November after absences of 10 and 5 years from the island. Examination in
March, 1974, showed moderately advanced ALS, including
pseudobulbar palsy, tongue fasciculations, moderate atrophy of the arms and shoulders, and marked spasticity of
the legs, with Hoffmann and Babinski reflexes present. He
died in November, 1974, at the age of 49. Postmortem
examination showed typical findings of ALS with neurofibrillary degeneration in the predicted areas.
Case 28 (NINCDS No. 9374)
This Chamorro man was born in Agana, Guam, in 1918,
and at age 19 joined the US Navy. During the next 24
years he travelled to the Far East, New Zealand, Australia,
and the US mainland until he retired to Guam in 1961. He
was first seen in August, 1975, at age 57, with a 3-month
history of slurred speech, slowness in swallowing, and
difficulty in buttoning his shirt. Neurological examination
showed prominent bulbar palsy and mild atrophy of the
hand muscles, especially on the right, but no spasticity or
hyperreflexia. Snout and palmomental reflexes were present. EMG showed neurogenic denervation in both arms.
Follow-up 1 year later showed rapid progression of the disease. He was ambulatory, but frequently choked o n his
618 Annals of Neurology Vol 8 No 6 December 1980
1. Annual Reports of the Surgeon General of the Navy to the
Secretary of the Navy. Washington, DC, US Government
Printing Office, 1900, p 210
2. Arnold A, Edgren D, Paladino V: Amyotrophic lateral sclerosis: fifty cases observed on Guam. J Nerv Ment Dis 117:
135-139, 1953
3. Benfante RJ, Hoffman PM, Garruto RM, Gajdusek DC: HLA
antigens in the Chamorros of the Mariana Islands and comparisons with other Pacific populations. Hum Biol 5 1:201212, 1979
3a. Brody JA, Hirano A, Scott RM: Recent neuropathologic observations in amyotrophic lateral sclerosis and parkinsonismdementia of Guam. Neurology (Minneap) 21:528-536,
197 1
4. Brody JA, Kurland LT: Amyotrophic lateral sclerosis and
parkinsonism-dementia in Guam. In Spillane J (ed): Tropical
Neurology. New York, Oxford University Press, 1973, pp
355-375
5. Chen K-M: Motor neuron involvement in parkinsonismdementia and its relationship to Guam ALS. In Japan Medical
Research Foundation (ed): Amyotrophic Lateral Sclerosis.
Tokyo, University of Tokyo Press, 1979, pp 319-344
6. Eldridge R , Ryan E, Rosario J, et al: Amyotrophic lateral sclerosis and parkinsonism-dementia in a migrant population from
Guam. Neurology (Minneap) 19:1029-1037, 1069
7. Garruto RM, Gajdusek DC, Chen K-M, Plato CC: Amyotrophic lateral sclerosis and parkinsonism-dementia in long
term Filipino migrants to Guam (abstract no. 90). In Proceedings of the 5th Asian and Oceanian Congress of Neurology, Manila, Nov 18-21, 1979. (Asia Pacific Congress series
No. 1). Amsterdam, Excerpta Medica, 1979, p 43
8. Gibbs CJ Jr, Gajdusek DC: Amyotrophic lateral sclerosis,
Parkinson's disease and the amyotrophic lateral sclerosisparkinsonism-dementia complex on Guam: a review and
summary of attempts to demonstrate infection as the etiology.
J Clin Pathol 25:suppl 6132-140, 1972
9. Hoffman PM, Robbins DS, Gibbs CJ Jr, Gajdusek DC,
Garruto RM, Terasaki PI: Histocompatibility antigens in
amyotrophic lateral sclerosis and parkinsonism-dementia o n
Guam. Lancet 2:717, 1977
10. Hoffman PM, Robbins DS, Nolte MT, Gibbs CJ Jr, Gajdusek
DC: Cellular immunity in Guamanians with amyotrophic lateral sclerosis and parkinsonism-dementia. N Engl J Med
299:680-685, 1978
11. Kurland LT: An appraisal of the neurotoxicity of cycad and
the etiology of amyotrophic lateral sclerosis o n Guam. Fed
Proc 31:1540-1542, 1972
12. Kurland LT, Mulder DW: Epidemiologic investigations of
amyotrophic lateral sclerosis. I. Preliminary report on geographic distribution, with special reference to the Mariana
Islands, including clinical and pathological observations.
Neurology (Minneap) 4:355-378,438-448, 1954
13. Mulder DW, Kurland LT, Iriarte LLG: Neurologic diseases on
Island ofGuam. US Armed Forces Med J 5:1724-1739,1954
13a. Plato C C , Reed DM, Elizan TS, Kurland LT: Amyotrophic
lateral sclerosis/parkinsonjsm-dementia complex of Guam.
IV. Familial and genetic investigations. Am J Hum Genet
19~617-632, 1967
14. Reed DM, Brody JA: Amyotrophic lateral sclerosis and
parkinsonism-dementia on Guam, 1945-1972: I. Descriptive
epidemiology. Am J Epidemiol 101:287-301, 1975
15. Reed D, Labarthe D, Stallones R: Health effects of westernization and migration among Chamorros. Am J Epidemiol
92:94-112, 1970
16. Reed D, Plaro C, Elitan T, Kurland LT: The amyotrophic lateral sclerosislparkinsonism-dementia complex: a ten-year
follow-up on Guam. Part I. Epidemiologic studies. Am J
Epidemiol 83:54-73, 1966
17. Rossman D L Increased fertility among amyotrophic lateral
sclerosis and parkinsonism-dementia complex cases on the island of Guam. PhD dissertation, Department of Anthropology and Human Genetics, University of Michigan, 1978
18. Smith RA, Gibbs CJ Jr, Kohne DM: In vitro-labeled D N A
19.
20.
21.
22.
for detection of polioviral genome in amyotrophic lateral sclerosis (abstract). Neurology 29:555-556, 1979
Torres J, Iriarte LL, Kurland LT: Amyotrophic lateral sclerosis
among Guamanians in California. Calif Med 86:385-388,
1957
Viola MV, Myers JC, Gann KL, Gibbs CJ Jr. Roos RP: Failure to detect poliovirus genetic information in amyotrophic
lateral sclerosis. Ann Neurol 5:402-403, 1979
White LR, Nemo GJ, Gibbs CJ Jr, Gajdusek DC, Brody JA:
Guamanian amyotrophic lateral sclerosis and parkinsonismdementia; search for a virus. Neurology 26:396, 1976
Yase Y ALS in the Kii Peninsula: one possible etiological
hypothesis. In Japanese Medical Research Foundation (ed):
Amyotrophic Lateral Sclerosis. Tokyo, University of Tokyo
Press, 1979, pp 307-318
Garruto et al: ALS in Chamorro Migrants
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