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Amyotrophic lateral sclerosis and parkinsonism-dementia among Filipino migrants to Guam.

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Amyotrophic Lateral Sclerosis
and Parkmsonism-Dementia among
Filipino Ahgrants to Guam
Ralph M. Garruto, PhD," D. Carleton Gajdusek, MD," and Kwang-Ming Chen, M D t
Amyotrophic lateral sclerosis (ALS)has occurred in 9 Filipino migrants to Guam 1to 29 years after their arrival and
parkinsonism-dementia (PD) in 2 migrants 13 and 26 years after arrival. Seven additional Filipino patients developed more classic Parkinson disease (P) 5 to 24 years after their migration to Guam. Furthermore, 10 partFilipino patients who were born on Guam of Filipino and Chamorro parentage developed ALS, while 6 such partFilipino patients developed PD. An estimate of the average annual crude mortality rate for ALS among Filipino
migrants was approximately six times that of the continental United States, yet half that currently observed among
Chamorros living on Guam. A majority of all migrant patients were born in northwestern Luzon in the Philippine
Islands, indicating the desirability of an intensive field epidemiological investigation in that area.
Garruto RM, Gajdusek D C , Chen K-M: Amyotrophic lateral sclerosis and parkinsonism-dementia among
Filipino migrants to Guam. A n n Neurol 10:341-350, 1981
During the past two decades, an increasing number
of cases of amyotrophic lateral sclerosis (ALS) and
parkinsonism-dementia (PD) have been identified in
long-term Filipino migrants to Guam [7, 121. Because ALS and PD are known to occur in unusually
high incidence among the Chamorro people of Guam
[ l , 2, 14, 18, 201 and among long-term Chamorro
migrants from Guam [9, 11, 231, the appearance of
these disorders in long-term Filipino migrants represents new information concerning their possible
cause. We found 9 cases of ALS and 2 of P D in fullFilipino migrants to Guam and 10 cases of ALS and 6
of P D in part-Filipino patients born on Guam of
Filipino and Chamorro parentage. An additional 5
full-Filipino migrants developed classic Parkinson
disease, and 2 others, parkinsonism with evidence of
organic dementia. For convenience, this last group of
7 patients will be referred to as having parkinsonism
with or without dementia (P).
The search for ALS and P D in Filipino migrants
included extensive inquiry and referral of patients by
the NINCDS Research Center staff on Guam, inquiry within the Filipino community, and referrals by
both Filipino and Guamanian physicians. Our observations provide information on the length of exposure to environmental conditions on Guam and the
latency period in migrants prior to onset of disease if
cultural or environmental variables o n Guam are a
cause of their illness. The epidemiological and demographic profiles and clinical histories of all 18 fullFilipino patients are presented. The 10 cases of ALS
and 6 of PD in patients of mixed Filipino and
Chamorro parentage are tabulated and analyzed
epidemiologically and clinically but without case
summary presentations.
From the "Laboratory of Central Nervous System Studies, National Institute of Neurological and Communicative Disorders and
Stroke, National Institutes of Health, Bethesda, MD 7-0205, and
the tN1NCD.S Research Center, Tamuning, Guam 96911.
Received Aug 7, 1980, and in revised form Jan 19, 1981. Accepted for publication Jan 23, 1981.
Migration History
Early immigration of Filipinos to Guam occurred
following Magellan's conquest of the island in the
sixteenth century. By 1783, as a result of the
Spanish-Chamorro wars, severe typhoons, and
epidemics, the original Chamorro population had
been reduced to such an extent that nearly 20% of
the remaining Guamanians were direct descendants
of Filipino-Chamorro unions, perpetuating the
known genetic relatedness between the two groups
[ 3 , 19, 21,221. A resurgence of Filipino migration to
Guam has occurred since World War 11; the estimated Filipino population of 569 in 1940 had increased to more than 10,000 in 1970 [24, 271.
Between 1950 and 1960 there were 7,000 to
7,500 male Filipinos o n Guam [25,26]. According to
the 1970 U.S. Census [27], 10,172 Filipinos were
living on the island, but age and sex distributions
were not available. Recently, however, Dr Steven
Lutes of the Institute of Behavioral Science at the
Address reprint requests to Dr Garruto, Bids 36, Room 5B25,
National Institutes of Health, Bethesda, MD 20205.
0364-5 134/8l/l00341-10$Ol.25 @ 1981 by the American Neurological Association
341
i
/
"
MARIANA
;ISLANDS
-._
P-.
-..
Sawan
Tinla"
ROW
o\c"am
ALSiPD Focur
Place of Onset of Patients
by Case Number
0 ALS
A
PD
U P
/J=--?yJ
AUSTRALIA
University of Colorado has surveyed the Filipino
population on Guam (personal communication and
unpublished data) and calculated that for the year
1970 there were 9,215 males and 2,375 females, a
total figure close to that of the U.S. census. The estimate of the male Filipino population included 3,100
short-term contract workers and 1,500 illegal aliens.
Additionally, 1,200 male Filipinos were below the
age of 25 years. Thus, approximately 8,000 represents a reasonable estimate for the 1770 adult male
Filipino population at risk.
Of approximately eighteen major villages on
Guam, Filipino settlement has occurred mainly in
those located in the northern and central regions (Fig
1). Currently on Guam there are several Filipino organizations which represent the various geographic
areas and linguistic dialects of the migrants. They include Metro Manila (Tagalog), Cavite (Tagalog),
Ilocos (Ilocano), Pangasinan (Pangasinan), Visaya
(Hiligayon), Samar-Leyte (Wary-wary), and Camarines-Albay (Bicol). The migration history for approximately two-thirds of the Filipino ALS and P D patients indicates that they arrived on Guam from the
Luzon region of the Philippine Islands during the
postwar era between 1946 and 1950 (Table 1, Fig 2).
342 Annals of Neurology Vol 10 N o 4 October 1981
F i g 1 . Place of onset on Guam of amyotrophic lateral sclerosis
(ALS), parkinsonism-dementia (PD),and parkinsonism with
or without dementia (P) i n Filipino migrants.
O n arrival, many were employed as contract construction workers for the U.S. military. However,
migration was often a two-step process. Many initially left the Philippine Islands as young adults and
resided in Hawaii for about 2 0 years or more before
migrating to Guam, where they remained an average
of approximately 17 years prior to onset of their disease.
All 18 cases of ALS, PD, and P among Filipino migrants were in males. This sex distribution is not unusual, as reflected by U.S. Censuses for Guam
showing a male to female sex ratio among Filipinos
o f 2 8 : 1 i n 1 9 5 0 a n d 4 : 1 i n 1770[25,27].Amongthe
16 cases of ALS and P D in Filipinos of mixed parentage or grandparentage who were born on Guam, the
father or grandfather was always a Filipino migrant,
the mother or grandmother a native Guamanian
Chamorro. This further reflects the overwhelmingly
male migration of Filipinos to t h e island.
Clinical a nd Neuropathological Evaluation
During nearly 30 years of intensive study of ALS and
PD on Guam, the staff of the NINCDS Research
Center has paid keen attention to the development of
either disease in persons of other than Chamorro ancestry [4-6, 10, 201. All cases identified within the
migrant community have been carefully and intensively pursued. The search for ALS and PD in
Filipino migrants has included extensive inquiry by
members of the NINCDS Research Center staff and
referral of patients by local Filipino and Guamanian
physicians, as well as continued epidemiological
monitoring for the past three decades.
The Appendix presents clinical summaries for the
18 cases (9 ALS, 2 PD, and 7 P) in long-term Filipino
migrants to Guam. Clinical summaries are not provided for the 16 patients (10 ALS and 6 PD) of mixed
Filipino-Chamorro ancestry who were born on
Guam, but relevant clinical and epidemiological data
pertaining to these cases are summarized in Table 2.
All Filipino migrants were examined by at least one
qualified neurologist from the NINCDS Research
Center. Nine cases were diagnosed clinically as ALS
and 2 as P D with clinical courses similar to those of
“pure” Chamorros. One P D patient (Case 11) had
evidence of psychiatric problems as well. Among the
7 cases identified as P, 5 patients had typical Parkinson disease, 1 had marked organic dementia with
minimal extrapyramidal signs, and another had parkinsonism, dementia, and progressive supranuclear
palsy.
Four of the patients with ALS and both with PD
were autopsied. Two ALS patients had mild
neurofibrillary changes in the characteristic distribution seen in Guamanian ALS [15]. Two others had
only the motor neuron loss seen in sporadic or classic
ALS. One of the 2 patients with P D (Case 10)
showed diffuse neuron loss, advanced gliosis and
demyelination, and depigmentation of the substantia nigra, with the characteristic distribution of
neurofibrillary changes seen in Guamanian PD ([ 131
and Makifuchi T: personal communication, 1980);
this case represents both clinical and neuropathological PD in a non-Chamorro. The remaining PD patient (Case l l ) demonstrated severe loss of cortical
neurons, gliosis, and degeneration of white matter in
the cerebral hemisphere and brainstem, in addition
to degeneration of the substantia nigra. Only a few
neurofibrillary tangles were seen in this patient, but
the distribution was characteristic of Guamanian
PD ([5] and Hirano A: personal communication,
1980). Two of the patients with P were autopsied,
and the neuropathological findings in both reflected
their clinical diagnosis. Of the remaining 10 patients,
3 were lost to follow-up (2 returned to the Philippine
Islands and 1 left for the U.S. mainland), 1 disap-
peared on Guam, 2 are still alive, and permission for
autopsy was denied in 4 cases.
The diagnoses of all 10 ALS and 6 P D patients of
mixed Filipino-Chamorro parentage were clinically
verified by an NINCDS neurologist. Four of the 10
ALS patients have been autopsied and showed
neuropathological changes consistent with Guamanian ALS. One patient is still living, and in the remaining 5, permission for autopsy was not obtained.
Among the 6 P D patients, 3 were autopsied and had
neuropathological confirmation of Guamanian PD,
2 are still living, and 1 is currently receiving
neuropathological study. All 16 patients of mixed
Filipino-Chamorro parentage had clinical courses and
pathological findings indistinguishable from those of
ALS or P D in “pure” Chamorros.
Epidemiological Findings a n d Discussion
Epidemiological and clinical data on the 18 Filipino
migrants who developed their disease after long-term
residence on Guam are presented in Table 1. As
noted, all were male, and they arrived on Guam generally between the ages of 30 and 45 years. Many of
them were born in the Ilocos region of northwestern
Luzon, and several migrated to and resided in Hawaii
prior to their immigration to Guam.
Since all known deaths from ALS in Filipino migrants have occurred during the past 13 years (2 recent patients remain alive), we estimate an average
annual crude mortality rate (partially age and sex adjusted) of at least 8 cases per 100,000 per year. Based
on the recent demographic survey of D r Steven Lutes
and the 1970 U.S. Census, this rate is approximately
six times that found in the continental United States,
yet only one-half the rate currently observed among
Chamorro males living on Guam. With only 2 cases
of P D occurring clinically in Filipino migrants, little
would be gained by calculating rates for this disorder.
The mortality rate for ALS in Filipino migrants is
only an estimate since the actual male population has
probably been underestimated due to growth of the
migrant population since 1970. Our inclusion of
3,100 short-term male contract workers, however,
tends to overestimate the population base. Therefore, these two factors tend to offset each other.
Migrants afflicted with ALS generally migrated to
Guam as middle-aged adults during the fourth and
fifth decades of life; they had a mean age at migration
of 38.2 years with a range of 23 to 60 years. The
mean age at onset was 54.9 years (range, 32 to 72)
with a duration of illness of 2.3 years (range, 2 to 3).
The mean number of years of residence on Guam
prior to onset was 16.8, with a range of 1 to 29 years.
Among migrants with PD, the mean age at migration
was 37.5 years. The mean age at onset was 57 years,
with a duration of 7 years, and the mean number of
Garruto et al: ALS and PD in Filipino Migrants 343
Table I . Summary of Amyotrophic Lateral Sclerosis, Parkinsonism-Dementia, and Parkinsonism
With or Without Dementia i n Long-term Filipino Migrants to Guam
Migration Summary Prior t o Onset
Birth
Case
No. a
NINCDS
Patient No.
Place
Year
Age
Arrived
Year
Arrived
M
Abra
Ilocos Sur
Ilocos Norte
Nueva Ecija
Pangasinan
Ilocos Norte
Albay
Pangasinan
Laguna
1903
1926
1914
1911
1911
1910
1917
1915
1944
43
23
32
35
36
37
46
60
32
1946
1949
1946
1946
1947
1947
1963
1975
1976
<1
M
M
Ilocos Sur
Ilocos Sur
1910
1910
36
39
1946
1949
26
13
1917
1908
1913
1910
1926
1909
1939
30
38
42
34
25
37
33
1947
1946
1955
1944
195 1
1946
1972
24
21
Sex
Years
on Guam
AMYOTROPHIC LATERAL SCLEROSIS
~
1
2
3
4
5
6
7
8
9
9379
946 1
9344
9181
92 10
9113
9037
9450
9432
M
M
M
M
M
M
M
M
~~~
29
29
26
22
22
17
3
2
PARKINSONISM-DEMENTIA
10
11
9402
9115
PARKINSONISM WITH OR WITHOUT DEMENTIA
12
13
14
15
16
17
9308
9350
FMN
91 17
9204
DPG
18
BVG
M
M
M
M
M
M
M
ilocos Sur
Ilocos N o r t e
Pangasinan
Ilocos Sur
Romblon
Isabela
Visaya
18
21
15
15
5
"Boldface numbers identify previously reported patients: Case 6 15, 101 and Cases 1 1 and 17 [lo].
P.I. = Philippine Islands; ALS = amyotrophic lateral sclerosis;NA = not available; PD = parkinsonism-dementia;P = parkinsonism with or
without dementia; D = dementia; PSP = progressive supranuclear palsy; NFT = neurofibrillary tangles.
years on Guam prior to onset of PD was approximately 20.
Onset of ALS in Filipino migrants is 3 years later
than that currently observed among Guamanian
Chamorros. The duration of illness is comparatively
short (2.3 years), only one-half that currently found
among Guamanian Chamorros (Garruto RM, unpublished data). By contrast, migrants with PD have
onset at the same age as that of the native Chamorro
population, and their course of illness is slightly
longer. For both ALS and PD, the exposure time to
environmental conditions on Guam prior to onset
may be as long as nearly three decades, with a mean
closer to two decades.
Occupations and residential history patterns
among the affected migrants did not appear pertinent. At the time of onset, both ALS and PD patients
resided in the northern and central parts of the island; no patient lived in the southern villages, where
the highest rates among Chamorros have occurred in
the past (see Figure 1). Occupational histories re-
vealed a wide variety of skilled and unskilled professions among the patients, including taxi and bus
drivers, farmers, construction workers, carpenters,
mechanics, plumbers, and miners. Interestingly, 2
patients had been boxers before coming to Guam,
Case 3 (ALS) full-time and Case 10 (PD) part-time;
the known association between boxing and dementia,
extrapyramidal signs, and neurofibrillary changes [81
caused us to take added care to avoid overinterpreting their findings. Both patients with Guamanian
ALS (Cases 3 and 6) and 1 with PD (Case 10)married
Chamorro women, while the other patients had
Filipino or Hawaiian spouses or remained single.
Those married to Chamorro women probably had
more exposure to local Chamorro customs and to
locally grown food items, especially those prepared
for special occasions or used as pharmacological
I agents in association with folk medicine practices.
In 1973, Dr Dwayne Reed obtained dietary information from the spouses of 6 Filipino patients with
ALS and PD. None of the patients ever ate cycad, a
344 Annals of Neurology Vol 10 No 4 October 1981
Onset
Death
Place
Age
Year
Age
Chalan Pago
Dededo
Agana Heights
Tamuning
Dededo
Agana Heights
Tamuning
Toto
Orote Point
72
52
58
57
58
54
49
62
32
1975
1978
1972
1968
1969
1964
1966
1977
1976
(Returned to PA.)
(Alive)
Yona
Siniana
62
52
1972
1962
70
58
Yigo
Tamuning
Dededo
Agat
Santa Rita
Yigo
Barrigada
54
59
60
55
40
52
38
197 1
1967
1973
1965
1966
1961
1977
~~~
60
59
61
57
51
64
Year
1974
1970
1972
1967
1968
1979
(Alive)
1980
1968
Clinical
Findings
Pathological
Findings
ALS
ALS
ALS
ALS
ALS
ALS
ALS
ALS
ALS
NA
NA
Guamanian ALS
NA
Classic ALS
Guamanian ALS
NA
Classic ALS
NA
PD
PD
PD
?PD
~
~~
(Lost on Guam)
70
1978
(Left Guam for U.S.)
67
1977
(Returned to P.I.)
55
(Alive)
traditional food prepared from the highly toxic nut of
the cycad palm (Cycas circinalis), and all reported frequently eating locally obtained fish. Otherwise, no
peculiar or common cultural practice, dietary pattern,
marriage practice, or any common occupational pattern or local residence history could be discerned.
It is difficult to determine if exposure of Filipino
migrants to the Guamanian environment has increased their risk of developing ALS o r PD, since few
epidemiological data are available on the incidence of
these disorders in the Philippine Islands. A single
nonsystematic survey of motor neuron disease has
disclosed a low prevalence rate in the Ilocos region of
the Philippines [17]. Yet the high incidence of ALS
among Filipino migrants to Hawaii, many of whom
were born in northwestern Luzon [16], the recent
impressions of Filipino neurologists that many of the
ALS cases seen in Manila are from the Ilocos area,
and the fact that 45% of our Filipino patients with
ALS and PD were born in the Ilocos region (see Fig
2 , Table 1) suggest the need for epidemiological in-
1964
P+D+PSP
P
D > P
P
P
P
P
NA
NA
NA
P + NFT
NA
P
NA
vestigation to establish incidence and prevalence
rates in northwestern Luzon. Additionally, without an
estimate of the proportion of Filipinos on Guam who
migrated from the Ilocos area, it is equally difficult to
establish whether individuals from this region have
an increased risk of developing disease after emigrating to Guam.
Table 2 summarizes the epidemiological and clinical data for Filipinos of mixed ancestry who were
born on Guam of Filipino (father or grandfather) and
Chamorro (mother or grandmother) descent. The 10
ALS patients had a mean age at onset of 49 years
(range, 32 to 62) with a mean duration of 6.9 years
(range, 2 to 24). The 6 PD patients had a mean age at
onset of 60.7 years (range, 55 to 71) with a mean
duration of 2.3 years (range, 1 to 4). Compared with
the ethnically “pure” Chamorros, the ALS patients
had a somewhat longer duration of illness, while the
P D patients had a shorter duration and were slightly
older at onset. Both disorders were equally distributed among males and females. Filipino patients of
Garruto et al: ALS and P D in Filipino Migrants
345
mixed parentage ate Chamorro foods and lived a
lifestyle undifferentiated from that of “pure”
Chamorros. We could not discern any common occupational or residential pattern among those affected. The high percentage of patients born in the
Agana area reflects the large proportion of the total
population residing in that area prior to World War
11.
The continuing decline in average annual crude incidence rates of both ALS and P D on Guam and the
upward shift in the average age at onset ([201 and
Garruto RM, unpublished data) suggests that toxic,
infectious, metabolic, or deficiency factors, or combinations of all these variables, are involved in
pathogenesis. A recent survey of the prevalence of
ALS among long-term Chamorro migrants indicated
that they remain at increased risk for developing disease after an exposure of at least 18 years to the
Guamanian environment, with a postmigration latency period that may be over three decades [ l l ] .
The present study of ALS and PD in Filipino migrants to Guam reveals an exposure of more than 13
346 Annals of Neurology Vol 10 No 4 October 1981
F i g 2. Birthplace of Filipino migrants with amyotrophic lateral sclerosis (ALS), parkinsonism-dementia (PD),andparkinsonism with or without dementia (P).
years to the Guamanian environment for all but 3 of
the 11 patients. This lends further support to the
idea that long-term exposure to the local environment may be a contributing factor. If environmental
factors on Guam are a cause of ALS and PD, then the
studies of both Chamorro migrants to the continental United States and Filipino migrants to Guam indicate that such individuals may become afflicted
regardless of whether they were exposed during
childhood and adolescence (as with the Chamorro
migrants) or as middle-aged adults (as with the
Filipino migrants). Without an intensive search for
ALS and P D in the northwestern Luzon region of
the Philippine Islands and the identification of either
disease in individuals of ancestry other than Filipino
or Chamorro, the implication that the Guamanian
environment is a causative factor remains speculative.
Table 2.Srmniary of Amyotrophic LateralSrlerosis and Parkinsonisrn-De?tienriain Patientj
oj' Mixed Filipino-Chumorro Purentage Who Were Born on Guam
Birth
NINCDS
Patient No. Sex
Ethnicity:
$6 Filipino
Place
Onset
Death
Clinical
Findings
Pathological
Findings
60
1955
66
1974
41
1952
(Alive)
70
1970
59
1954
55
1966
49
1958
65
1953
42
1966
ALS
ALS
ALS
ALS
ALS
ALS
ALS
ALS
ALS
ALS
NA
NA
NA
NA
ALS
NA
ALS
NA
ALS
74
1968
58
1959
(Alive)
62
1976
59
1961
(Alive)
PD
PD
PD
PD/ALS
PD
PD
NA
PD
NA
PD
PD
NA
Year
Place
Age
Year
Age
1895
1908
1911
1925
1900
1895
1911
1909
1888
1924
Dededo
Agana Heights
Agana Heights
Dededo
Santa Rita
lnarajan
Santa Rita
Barrigada
Mongmong
Barrieada
56
42
32
45
60
55
51
47
62
40
1951
1950
1943
1970
1960
1950
1962
1956
1950
1964
1894
1901
1907
1914
1902
1920
Sinajana
Yona
Mangilao
Mangilao
Talofofo
Merizo
71
57
64
61
55
56
1965
1958
1971
1975
1957
1976
Year
AMYOTROPHIC LATERAL SCLEROSIS
1155
9345
1152
0254
9091
0454
CDL
0358
1453
9042
M
M
M
F
M
F
F
F
M
F
50
50
50
50
50
50
50
25
25
25
Agana
Agana Heights
Agana Heights
Agana
Agana
Agana
Sumay
Barrigada
Agana
Agana
ALS
PARKINSONISM-DEMENTIA
~
~~~~
901 1
0459
9311
9386
096 1
9417
ALS
=
F
M
F
M
F
M
50
50
50
50
25
25
Sinajana
Yona
Agana
Agana
Talofofo
Merizo
amyotrophic lateral sclerosis; NA
=
not available; PD = parkinsonism-dementia.
Addendum
Since this manuscript was submitted, a 54-year-old unmarried Filipino man has been examined on Guam by D r
Eiichiro Mukai and one of us (K.-M. C.) and found to have
ALS. He was born in the province of Capiz in the Visayas
Islands of the Central Philippines in 1926 and migrated to
Guam in 1948 at age 22. He was a contract worker for the
U.S. Navy and lived in Camp Rojas for 16 years. More
recently he spent 16 years in the village of Merizo. Onset
of his disease was in August, 1980, when he began having
left shoulder pain and progressive left-sided weakness. By
December he had developed moderate dysarthria. H e denies any family history of neurological disease. This patient
developed ALS after 3 2 years on Guam.
We wish to thank Dr Chris C. Plato of the National Institute on
Aging, who assisted with this study while on Guam in 1977. Dr
Clarence J. Gibbs, Jr, provided advice and assistance throughout
the study, and Dr Richard T. Yanagihara and Dr Andres M.
Salazar critically evaluated the manuscript. The editorial assistance
of Doreen McMahon and graphic assistance of Jeff Etherton are
gratefully acknowledged. We also thank Dr Olivia T. Cruz, Jose
M. Torres, Mary E. Hernandez, Manuel T. Cruz, Francisco C .
Leon Guerrero, Luis T. Munoz, and Frances T. Vickers of the
NINCDS Guam Research Center staff, and the many cooperating
physicians o n Guam who referred cases to us or provided additional information o n existing cases.
Appendix: Clinical Summaries
Case I (NINCDS No. 9379)
A single male Filipino carpenter was born in Abra, Luzon,
in 1903, migrated to Hawaii in 1924, and then to Guam in
1946. In early 1975 he developed weakness of the left
hand. Examination in October of that year revealed mild
facial weakness, muscle atrophy, weakness, hyperreflexia of
all limbs, and extensor plantar responses. The sensory system was intact. Roentgenograms of the cervical spine were
negative, and electromyography (EMG) confirmed widespread, active denervation. He left for the Philippines in
December, 1975, and was lost to follow-up.
Case 2 (NINCDS No. 9461)
A male Filipino farmer born in Ilocos Sur, Luzon, in 1926,
migrated to Saipan in 1947 and to Guam 2 years later. He
married a Filipino woman and had four children. He
worked at various jobs, as a mechanic, painter, and
warehouse laborer. Early in 1978, at age 52, he noticed
stiffness of the extremities and muscle twitching. Examination in October of that year revealed typical spinal atrophic
and spastic type weakness without bulbar o r sensory involvement. Cervical spine roentgenograms were unremarkable, and EMG showed active denervation in both
upper and lower extremities. By January, 1980, he had developed pseudobulbar palsy and was confined to a wheelchair with marked atrophy and weakness in both lower extremities. Deep tendon reflexes and jaw jerk were
hyperactive and plantar responses were extensor bilaterally. The sensory system was intact. He is still alive.
Case 3 (NINCDS No. 9344)
A Filipino man was born in Ilocos Norte, Luzon, in 1914,
migrated to Hawaii in 1928, and became a boxer before
moving to Guam in 1946. O n Guam he worked as an auto
mechanic, married a Chamorro woman in 1948, and had
Garruto et al: ALS and PD in Filipino Migrants
347
eleven children. Examination in May, 1972, at age 58
revealed generalized fasciculations, weakness in both upper extremities, severe bulbar palsy, hyperreflexia, and
difficulty in walking. In December, 1973, he fell, and a
subdural hematoma was evacuated from the right frontotemporal area. He died of emaciation and bronchopneumonia with a course lasting 21/2 years. Postmortem
examination confirmed Guamanian ALS with scanty
neurofibrillary tangles.
Examination in September revealed weakness of the right
upper extremity, fasciculations, and hyperreflexia. Cranial
nerves were intact except for a hyperactive jaw jerk. Sensory functions were normal, and myelography was negative. EMG confirmed widespread active denervations
below the neck with normal motor and sensory conduction.
He returned to the Philippines in December, 1966, and
died in May, 1968. N o autopsy was performed.
Case 8 (NINCDS No. 9450)
Case 4 (NINCDS No. 9181)
A Filipino man was born in Nueva Ecija, Luzon, in 191 1,
migrated to Guam in 1946 as a contract worker on a U.S.
military base, married a Filipino woman in 1957, and had
five children. For 18 years he was employed an average of 3
or 4 days a week at a chemical plant smelting lead, brass,
aluminum, and zinc. Early in 1968, at age 57, he developed
progressive atrophy and weakness of the hands and legs.
Examination in 1969 revealed bulbar involvement, and the
following year he rapidly became bedridden, showing both
spastic and atrophic features in the entire spinal axis. He
died in May, 1970, with a clinical diagnosis of ALS. Autopsy was refused.
Case 5 (NINCDS No. 9210)
A male Filipino construction worker was born in Pangasinan, Luzon, in 191 1, migrated to Guam in 1947, married a
Filipino woman from the same province in Luzon, and had
six children. Early in 1969, at age 58, he noticed progressive weakness and atrophy of the left arm and leg and
slurred speech. Examination in September of that year revealed widespread fasciculations of the tongue, shoulders,
and arms, atrophy and weakness of the left hand and arm,
generalized hyperreflexia, bilateral ankle clonus, and extensor plantar responses. Within a year his speech became
barely intelligible. Detailed sensory examination and
roentgenograms of the cervical spine were normal. He
rapidly developed severe dysphagia and died in February,
1972, at the age of 61. Postmortem examination by D r
Asao Hirano revealed classic ALS without neurofibrillary
tangles.
Case 6 (NINCDS No. 91 13)
A male Filipino accountant born in Ilocos Norte, Luzon, in
1910, migrated to California in 1929, to Hawaii in 1930,
and then to Guam in 1947. He married a Chamorro woman
whose father and brother had died of ALS. They had six
children. In April, 1964, at age 54, he developed atrophy
and weakness of the right hand, which progressed to the
left side and involved bulbar structures within a year.
Within 2 years he became severely paralyzed, with marked
generalized atrophy, spasticity, and dysphagia. He died in
May, 1967, at the age of 57, after a total course of 3 years.
Postmortem examination by D r Asao Hirano confirmed
Guamanian ALS with neurofibrillary tangles.
Case 7 (NINCDS No. 9037)
This male Filipino carpenter was born in Albay, southern
Luzon, in 1917, married a Filipino woman, and had four
children. He migrated to Guam in 1963. In July, 1966, at
age 49, he noticed clumsiness of the right hand and arm.
348 Annals of Neurology
Vol 10 No 4
A male Filipino construction worker, former miner, and
farmer was born in Pangasinan, Luzon, in 1915. He migrated to Guam with his Filipino wife and three children in 1975. In October, 1977, at age 62, he noticed
difficulty in speaking and swallowing. Examination the following March showed progressive bulbar palsy with sparing
of the spinal motor neurons. By June, weakness of facial
and neck muscles, fasciculations of shoulder muscles, and
hyperactive reflexes had developed. He died in June, 1979,
at the age of 64. Postmortem examination demonstrated
classic ALS.
Case 9 (NINCDS No. 9432)
A Filipino man was born in Laguna, Luzon, in 1944, joined
the U.S. Navy in 1966, was stationed on the U.S. mainland,
and was subsequently transferred to Guam in 1976. He
married a Filipino woman and had one child. Shortly after
his arrival on Guam he developed weakness and fatigability
of the legs and tremulousness of the fingers. Examination in
May, 1977, showed generalized amyotrophy, weakness,
stuttering speech, and occasional fasciculations. EMG
showed normal conduction velocities and widespread denervation potentials. He left Guam in 1978 and was lost to
follow-up.
Case 10 (NINCDS No. 9402)
This Filipino man was born in Ilocos Sur, Luzon, in 1910,
and migrated to Hawaii in 1928, where he worked on a
sugar plantation for 12 years, and was a part-time boxer
until he migrated to Guam in 1946. He married a
Chamorro woman and had eight children. In 1972, at age
62, he developed bradykinesia, and 31/2 years later had developed tremors of the left hand and chin. Examination in
December, 1975, revealed masked facies, rhythmic 4 H z
tremors of the chin and left hand, marked bradykinesia,
motor arrest, and poor postural reflex. Reexamination the
following June showed bilateral tremors, a prominent
snout reflex, and dysarthria. In November, 1977, dementia, stooped posture, and poor ambulation were observed.
By December, 1978, he presented with urinary and fecal
incontinence and had lost interest in his surroundings.
Plantar responses were extensor bilaterally. He became
vegetative with marked flexion contractures, extensive decubiti, and amyotrophy. He died in January, 1980.
This case was clinically indistinguishable from classic P D
in a Guamanian Chamorro. Postmortem examination by D r
Takao Makifuchi, reviewed by Dr Hirano, revealed diffuse
neuron loss, advanced gliosis and demyelination, and depigmentation of the substantia nigra with the characteristic
distribution of neurofibrillary tangles seen in Guamanian
PD. This is the first case in which both clinical and
October 1981
neuropathological observations in a non-Chamorro have
been consistent with a diagnosis of PD.
Case 1 1 (NINCDS No. 91 15)
A male Filipino taxi driver was born in Ilocos Sur, Luzon, in
1910, migrated to Hawaii in 1931, married a Hawaiianborn woman, and had one child. He remained in Hawaii 2 8
years until his migration to Guam in 1949. He presented in
1962, at age 52, with marked bradykinesia, stooped posture,
masked facies, absent arm swing on the right, moderate cogwheel rigidity, and mild tremor of the hands, especially on the right. An initial diagnosis of idiopathic Parkinson disease was made. By August, 1963, he was confined to
the extended care facility at Guam Memorial Hospital with
marked disorientation to time, place, and person. Gradually he lost his postural reflexes and developed apraxia of
gait, gegenhalten, grinding of the teeth, and a voracious appetite. Two years later he had developed startle responses
to visual stimulations. The electroencephalogram (EEG)
showed 4 to 5 H z low-voltage theta waves in brief runs but
no periodic burst-suppression pattern. Reexamination 1
year later revealed stupor, marked flexion contractures
with fetal posturing, marked glabellar and snout reflexes,
and startle response to visual stimulation. Deep tendon reflexes were brisk, with extensor plantar responses. He remained vegetative and died in 1968.
Postmortem examination by D r Hirano revealed a wet
brain weight of 950 gm; widespread, severe neuron loss
throughout the entire hemisphere with advanced gliosis;
depigmentation of the substantia nigra and locus ceruleus;
and gliosis of pontine and olivary nuclei unassociated with
neuron loss. Neurofibrillary degeneration was minimal. A
few senile plaques were seen in the frontal and parietal
lobes. Lewy bodies were absent. Sections of the spinal cord
revealed bilateral degeneration of the pyramidal tracts and
degeneration of Goll’s tracts and the posterior roots at the
lumbosacral level, the latter thought to be related to malnutrition, avitaminosis, or both. D r Hirano concluded that
despite the characteristic clinical course, the neuropathological changes were atypical for Guamanian PD.
Case 12 (NINCDS No. 9308)
This male Filipino carpenter was born in Ilocos Sur, Luzon,
in 1917 and migrated to Guam in 1947 at age 30. He married a Filipino woman and had three children. In 1971, at
age 54, he noted slowing of all movements and a tendency
to fall. Examination in December of that year revealed
masked facies with staring eyes, low voice, bradykinesia,
and marked retropulsion. Eye movments were limited,
especially in vertical gaze. Reexamination in January, 1973,
revealed dementia; hypokinetic speech with perseverations; a tendency to retropulsion; minimal rigidity; vertical
gaze paralysis; positive snout, palmomental, and Hoffman
reflexes; dyskinesia; and absent tremors. In October, 1973,
he wandered outside his house and never returned, and has
been listed as missing and presumed dead.
Case 13 (NINCDS No. 9350)
A male Filipino bus driver was born in Ilocos Norte,
Luzon, in 1908, migrated to Hawaii in 1942, and then to
Guam in 1946. He married a Chamorro woman and had
seven children. In 1967, at age 59, he developed rhythmic
tremors of the left hand. Examination in October of
that year revealed masked facies, mild cogwheel rigidity
in all extremities, pill-rolling tremor, and generalized
hyperreflexia. In 1969 he was confined to a mental institution for a “schizophrenic reaction” and was treated with
Thorazine and Cogentin. Since then h e was repeatedly reconfined to a mental institution for violent, incoherent, and
agitated behavior. During brief intervals he appeared to be
well oriented except for a tendency to perseverate. Examination revealed no evidence of cerebrovascular or spaceoccupying lesions. He was last seen in March, 1976, with
progression of extrapyramidal signs and early dementia. He
left Guam in 1977 and died in the Philippines in October,
1978.
Case 14 (FMN)
A male Filipino machinist was born in Pangasinan, Luzon,
in 1913. He married a Filipino woman and had five children prior to his migration to Guam in 1955. Early in 1973,
at age 60, his family noticed memory impairment, generalized slowing of movements, and soft, slow speech. Examination in February, 1974, showed dementia, hypokinetic
speech, and mild to moderate bradykinesia. Tremor was
not observed. H e was last seen in January, 1975, with
minimal progression of his disease. He left for the U.S.
mainland in August of that year and was lost to follow-up.
Case 15 (NINCDS No. 91 17)
A Filipino man was born in Ilocos Sur, Luzon, in 1910,
migrated to Hawaii in 192 1, to California 5 years later, and
then to Guam in 1944. H e married rwice to Chamorro
women and had two children. In 1965 he developed stiffness in his legs and slowness in walking. Examination in
1966, at age 56, showed marked bradykinesia, hypokinetic
dysarthria, generalized rigidity with cogwheeling, mild
hyperreflexia, and no tremor. His mental status and EEG
were normal. He moved to California in May, 1967, where
he was treated for Parkinson disease at several Veterans
Administration hospitals but died of bronchopneumonia
and congestive heart failure 10 years later. Postmortem examination revealed mild neuron loss and gliosis in the
cerebral cortex, occasional neurofibrillary tangles and
granulovacuolar changes in the hippocampus, and depigmentation of neurons and Lewy bodies in the substantia
nigra. Lewy bodies were also seen in the locus ceruleus.
Neurofibrillary changes were not seen in the subcortical
areas and brainstem.
Case 16 (NINCDS No. 9204)
This male Filipino soil analyst was born in Romblon in
1926, migrated to Guam in 1951, married a Filipino
woman, and had three children. In 1966, at age 40, he
noticed resting tremors of the right hand. O n e year later,
his face became stiff and his speech was slow and soft. Examination in December, 1969, revealed an alert, welloriented man with fine tremor, immobile facies, hypokinetic and soft speech, moderate rigidity with cogwheeling
more on the right, and mild bradykinesia. He was lost to
follow-up in 1970 when he returned to the Philippines.
Garruto et al: ALS and PD in Filipino Migrants
349
Case 17 (DPG)
This male Filipino plumber was b o r n i n Isabela, Luzon, i n
1909, migrated t o G u a m i n 1946, married a C h a m o r r o
woman, and had ten children. In 1961, at age 52, h e
noticed increasing stiffness of the right hand, slowness of
speech, bradykinesia, and tremor. Examination in October,
1963, showed masked facies, positive glabellar and snout
reflexes, hyperactive jaw jerk, bradykinesia, s t o o p e d posture, generalized hyperreflexia, and atrophy of t h e hand
muscles. Plantar responses were negative bilaterally. He
was mentally clear b u t depressed. Reexamination the following February revealed progression of truncal ridigity
and depression, b u t hyperreflexia and muscle atrophy remained unchanged. In a depressed state, he hanged himself
nine months later.
Postmortem examination by Dr H i r a n o demonstrated
classic Parkinson disease with abundant Lewy bodies and
intranuclear eosinophilic inclusions i n t h e substantia nigra
and locus ceruleus. A n extensive search for neurofibrillary
tangles in predilected areas disclosed only a few in t h e tegm e n t u m of the pons.
Case 18 (BVG)
This male Filipino electrician was born in the Visayan islands in the central Philippines in 1939, married a
Filipino-Chinese woman from t h e same area, and had six
children. T h e y migrated t o G u a m in 1 9 7 2 . In 1 9 7 7 , a t age
38, he noticed stiffness of his left a r m and intermittent
tremors of the left fingers and wrist. Examination i n May,
1977, revealed decreased arm swing, clumsy rapid movements of the fingers and feet, and mild cogwheel rigidity,
all on the left. Reexamination in August, 1979, showed
some progression of his left-sided hemiparkinsonism despite Sinemet therapy. Minimal rigidity was present o n t h e
right side. No evidence of dementia was found. He is still
alive.
References
1. Annual Reports of the Surgeon General of the Navy to the
Secretary of the Navy. Washington, DC. US Government
Printing Office, 1900, p 2 10
2. Arnold A, Edgren D, Paladin0 V: Amyotrophic lateral sclerosis: fifty cases observed on Guam. J Nerv Menr 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 51:201212, 1979
4. Brody JA, Chen K-M: Changing epidemiologic patterns of
amyotrophic lateral sclerosis and parkinsonism-dementia on
Guam. In Norris FH Jr, Kurland LT (eds), Motor Neuron
Diseases: Research on Amyotrophic Lateral Sclerosis and Related Disorders. New York, Grune & Stratton, 1969, pp
61-79
5. Brody JA, Hirano A, Scott M: Recent neuropathologic observations in amyotrophic lateral sclerosis and parkinsonismdementia of Guam. Neurology (Minneap) 21:528-536, 197 1
6. 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
7. Chen K-M, Garruto RM, Gajdusek DC, Nakano I: Amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia
350 Annals of Neurology Vol 10 No 4 O c t o b e r 1981
(PD) in Filipino migrants on Guam (abstract). Neurology
30:438, 1980
8. Corsellis JAN, Burton CJ, Freeman-Browne D: The aftermath of boxing. Psycho1 Med 3:270-303, 1973
9. Eldridge R, Ryan E, Rosario J, Brody JA: Amyotrophic lateral
sclerosis and parkinsonism-dementia in a migrant population
from Guam. Neurology (Minneap) 19:1029-1037, 1969
10. Elizan TS, Chen K-M, Mathai KV, Dunn D, Kurland LT:
Amyotrophic lateral sclerosis and parkinsonism-dementia
complex: a study in non-Chamorros of the Mariana and
Caroline Islands. Arch Neurol 14:347-355, 1966
11. Garruto RM, Gajdusek DC, Chen K-M: Amyotrophic lateral
sclerosis among Chamorro migrants from Guam. Ann Neurol
8:612-619, 1980
12. Garruto RM, Gajdusek DC, Chen K-M, Plato CC: Amyotrophic lateral sclerosis and parkinsonism-dementia in longterm Filipino migrants to Guam. Abstract no. 90 of the Fifth
Asian and Oceanian Congress of Neurology, Manila, The
Philippines, Nov 18-2 1, 1979 (Excerpta MedicalAsia Pacific
Congress Series no. 1). Amsterdam, Excerpta Medica, 1979, p
43
13. Hirano A, Malamud N , Kurland LT: Parkinsonism-dementia
complex, an endraic disease on the island of Guam. 11.
Pathological features. Brain 84:662-679, 1961
14. 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
15. Malamud N , Hirano A, Kurland LT: Pathoanatomic changes
in amyotrophic lateral sclerosis on Guam. Arch Neurol
5:401-415, 1961
16. Matsumoto N , Worth RM, Kurland LT, Okazaki H:
Epidemiologic study of amyotrophic lateral sclerosis in
Hawaii: identification of high incidence among Filipino men.
Neurology (Minneap) 22:934-940, 1972
17. Marsumoro N , Yase Y, Yasui M: Preliminary survey of motor
neuron disease in Ilocos Norte, Philippine Islands. Wakayama
Med Rep 15:181-185, 1972
18. Mulder DW, Kurland LT, Iriarte LLG: Neurologic diseases on
Island ofGuam. US Armed Forces Med J 5:1724-1739,1954
19. Plato CC, Cruz M: Blood group and haptoglobin frequencies
of the Chamorros of Guam. Am J Hum Genet 19:722-731,
1967
20. Reed DM, Brody JA: Amyotrophic lateral sclerosis and
parkinsonism-dementia on Guam, 1945- 1972: 1. Descriptive
epidemiology. Am J Epidemiol 101:287-301, 1975
21. Spoehr A: Marianas prehistory: archaeological survey and excavations on Saipan, Tinian, and Rota. In Fieldiana: Anthropology, vol48. Chicago, Natural History Museum, 1957
22. Thompson L Guam and Its People. Princeton, NJ, Princeton
University Press, 1947
23. Torres J, Iriarte LLG, Kurland L T Amyotrophic lateral
sclerosis among Guamanians in California. Calif Med
86:385-388, 1957
24. US Bureau of the Census: Census of Population, General
Population Characteristics, Guam. Washington, DC, US
Government Printing Office, 1940
25. US Bureau of the Census: Census of Population, General
Population Characteristics, Guam. Washington, DC, US Government Printing Office, 1950
26. US Bureau of the Census: Census of Population, General
Population Characteristics, Guam. Washington, DC, US
Government Printing Office, 1960
27. US Bureau of the Census: Census of Population, General
Population Characteristics, Guam. Washington, DC, US Government Printing Office, 1970
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