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Sport Science

Parkinson Disease In West Sumatera and Kerinci An Epidemiological Apprasial

PARKINSON DISEASE IN WEST SUMATERA AND KERINCI
AN EPIDEMIOLOGICAL APPRAISAL

Basjiruddin. A

Abstract
Etiology of Parkinson disease (PD) is not clear, although there are some hypotheses regarding its etiopathogenesis.

Occupational environment, pesticides, exposures to toxic chemical substance such as N-methyl 4-phenyl 1,2,3,4-

tetrahydropyridine (MPTP) group seem to support these hypotheses. The disease is found all over the world, is more prevalent among white people, but relatively less frequent among black and oriental populations. There are variations in male to female ratio, in which male is two or three times more often than females, but never exceeds three times. Age of onset usually between 50-70 years, more often in 70-79 year group, but rarely in people less than 30 years old. For every 100.000 population,mincidence is 20, prevalence is between, and mortality is between 0.5-3.8. There is hereditary factor involvement in the development of this disease.

This study was designed to evaluate clinical symptoms in relation to epidemiological and environmental factors. The survey included cases from two major hospitals and a private clinic in Padang. Patients surveyed came for the province of West Sumatera and the Kerinci County in Jambi province, which was included because of their closeness to West Sumatera regarding health services. The diagnosis was established using Hughes criteria, and the stadium was made according to Hoehn & Yahr modification.
We found 59 cases of PD, including two siblings and their mother, with age 56.5 ± 14.8 years (mean ± 1 SD), and range

between 18-85 years. Ten per cent of cases were under 40 years old. Most of the first symptoms of PD were experienced within age group of 55-64 years. There were 30 males (50.8%) and male: female ratio was 1.03. Majority (57.7%) of patients came from rural areas, in which the main occupation was farming, with frequent exposure to MPTP, drinking soil water, poor-economic conditions, and cool weather. Twenty patients were in stage I (40.7%) and two were in stage V (3.4%). There significant correlation between disease stages with the duration of PD (P = 0.0006) and with the patient’s ages (P =0.0015). The most prevalent comorbidity was hypertension (49.2%), followed by stroke (8.5%). We conclude that PD is associated with poor environmental factors, and its severity is related to age and duration of illness.

Introduction
Parkinson disease (PD) is a degenerative disease of extra-pyramidal system, which is most often found among the elderly (1.2).

Waters (1999) hypothesized that PD comprises 80% of all parkinsonism with signs of tremor at rest, rigidity, bradykinesia, and lacks of postural reflexes, while establishing the diagnosis only needs two out those four signs (3). This typical signs usually preceded by non-specific symptoms such as general malaise, muscle spasms, tightness or cramps, focal dystonia, loss of skillful

, sensory signs, and probably psychiatric signs such as anxiety or depression (4). The diagnosis is established using

history and physical examination. However, there is no specific examination to confirm or to deny the diagnosis of PD (5). The discovery of levodopa is a big triumph in the treatment of PD, but the drug itself has several drawbacks such as the side effects of dyskinesia, motor fluctuations, neurotoxicity up to freezing stage, easily falling down, and dementia.
The symptoms usually start on one side of the body which spread afterwards; seldom do they start symmetrically (5.6).

Tremors at rest felt by patients even before it can be seen, occur in the muscles of the face, tongue, jaws, and back of the neck. Rigidity that follows causes the patient to move very slowly. Fahn et al. (1998) concluded that clinical manifestations occurs as follows: unilateral onset (hemi parkinsonism), tremor at rest, absence of other neurological sign such as spasticity or Babinski sign, atypical speech disturbance, absence of laboratory or radiological abnormality, slow progression, dramatic response to levodopa, and preservation of postural reflexes early in the illness.(5).

Other pathological changes often found in PD are reduction of neuronal cells, gliosis, and lack of melanin in substantia nigra especially in ventrolateral putamen. Microscopically there is lacking of neurons in compact zone, while the living neurons seem be abnormal and contain intracytoplasmic hyalines (Lewy bodies). Other changes include diffuse reduction of neuronal cells especially in locus caeruleus and in dorsal motor nucleus of vagal nerve. Dopaminergic nucleus in ventral tegmentum also shows reduction of neurons and formation of Lewy bodies (6).
There are no explanations offered regarding how degeneration occurs. Some of the hypotheses suggest the role of non-

conventional viral infection, abnormal reactions to the virus, endogenous substance intoxication, environmental factors, genetic, combination of several factors, and premature senility (5,6). Predisposing factors are thought to be excess work, cool weather, grief, rigid personality, drinking soil water, and the use of chemicals in pesticides or fertilizers by farmers (7). Al Bunyan (2000) suggested four theories related to the occurrence of PD, i.e. genetic predisposition, neuronal erosion in aging, lack of anti-oxidative mechanism, and environmental insult. All of these could be coupled with trigger factors such as stress, trauma, and toxins (8).

Epidemiology surveys showed that PD occurs all over the world. The study was conducted most often in Caucasian population, northern Europe, or Anglo-Saxon areas. In defining the frequency of diseases, prevalence and incidence are two indicators most often used. Prevalence is used as a ratio showing the number of cases per 100.000 populations in a given time, while demonstrates the number of new cases within one year per 100.000 populations. However, estimating the incidence is proven to be a very difficult and very time consuming. Frequency of mortality is the number of deaths per 100.000 populations in a year.

Prevalence, incidence and mortality for a population are known as crude rates, and these indicators can only be counted for certain subgroups of population, such as male or female at certain ages. The crude prevalence ratio of PD is higher among white people, however at older ages it is similar to other population. PD prevalence among Japanese and Chinese people is lower than the Caucasians (9). Most of the patients are 50-70 years, with the first symptoms occur at 58-62 years. Incidence rate is very low under 30 years, and very high at 70-79 years. The presence of risk factors increases the incidence by 1-2%. At a much older age the incidence was lowered, this phenomenon suggests a sign to the pathogenesis (9).

In conducting the epidemiological studies on PD, there are several difficult factors to consider. Those are: problem with the diagnosis, clinical manifestations have long latent phase, and the disease itself belongs to older people which means the number of living member of the family has been reduced. (7). In industrial countries, PD attacks 0.1-0.5% of the population in general, more than 1% of population over 65 years, with the incidence rate of 4.5-21 per 100.000 population per year. Wide range the incidence rate was due to variations in research design and diagnostic criteria. In general, prevalence is estimated between 18 to 328 per 100.000, while a survey in China in 1983 revealed an incidence of 44 per 100.000. According to WHO (1997), worldwide incidence for PD is 20 and prevalence is between 100 and 200 per 100.000 population. The incidence is higher in males, whites, and certain industrial areas. Fifteen to 20% of PD sufferers would develop a dementia similar to those that happen in Alzheimer disease (10).

Mortality rate of PD varied among nations between 0.5 to 3.8 per 100.000 populations. However, the data cannot be used as main reference because very small number of PD is reported in death certificates, and because differences in reporting the diagnosis according to the International Classification of Diseases (ICD) between countries (7, 9).

In Indonesia, there are no secure epidemiological data available, as there has been no study regarding risk factors for PD. It isimportant to consider the writing of Flechner (1986) on clinical epidemiological studies, by interpreting scientific observation, gathering clinical occurrences of PD in the population, making an analysis on it, and by implementing clinical observation to make a valid clinical decision (11).

In this regard, we have gathered clinical epidemiological data on PD from the province of West Sumatera and the district ofKerinci, province of Jambi, for the development of a more complete clinical epidemiological study.

Materials and Methods
Most of the population of West Sumatera and Kerinci live in rural areas as farmers, and a relatively small proportion live in

urban areas. All of PD patients admitted to Neurology Departments of M. Djamil Hospital, Yos Sudarso Hospital, and private

clinics in Padang were included in the survey. Patients phenothiazine medication were excluded. The study was conducted from

March 1st, 2000 to February 28th, 2002.
Data evaluated include patient identity, sex, age, address, occupation and education. Age was classified according to WHO

(12). Also surveyed was the onset of PP symptoms, and other accompanying diseases.
Neurological status was assessed using the criteria based on the Consensus on the Management of Parkinson Disease (2002),

in which three out of four signs (tremor, rigidity, bradykinesia, and lack of postural reflexes) were found. Progress of the disease

was measured using Hoehn & Yahr Staging of Parkinson Disease.
Results
During the two-year period we have found 59 patients consisted of 30 males (50.8%) and 29 females (49.2%). Male to female

ratio was 1.03:1. Mean age of patient was 56.6 years (14.8 year standard deviation) with range from 18 to 87 years. Most

patients were of Malay origin (88.1%) and the rest was Chinese. Almost half (44.1%) of patient did not go to high school, while

a minority (8.5%) were university graduates (Table 1). There are two brothers with PD whose mother also a victim of PD.

Table 1. Distribution of patients according to age, origin and education
No.    Basic data    Variants    Total    %
1    Sex    Male
Female    30
29      50.8
49.2
2.    Ethnicity    Malay      – Male
– Female
Chinese   – Male
– Female    27
25
3
4     45.8
42.3
5.1
6.8
3.    Education level    None
Elementary school
Junior High school
Senior High School
University graduates    6
20
11
17
5    10.2
33.9
18.6
28.8
8.5

There are six patients (10.2%) with age under 35 years old, although the majority was 55 years and over (66.1%). Four

patients at age group 15-24 (6.8%) consisted of a housewife who also works as part time farmer, two males who work as

farmer, and one school dropout. Two patients at age group of 25-34 years (3.4%) consisted of a Chinese women works as a

housewife, and a Malay man who is self employed. Several patients at age group 45-54 and 55-64 years wait several years

before seeking help for their symptoms (Table 2).

Table 2. Age distribution of first visit and onset of symptoms
No.
Age group (yr)
n    %
Onset of symptoms    %

1
2
3
4
5
6
7
8    15-24
25-34
35-44
45-54
55-64
65-74
75-64
85-94    4
2
1
13
22
12
4
1    6.8
3.4
1.7
22.0
37.3
20.3
6.8
1.7    4
2
1
17
24
10
0
1    6.8
3.4
1.7
28.8
40.7
16.9
0.0
1.7
Total    59    100    59    100

Patients are from five counties (57.6%) and three cities (42.4%) in West Sumatera and Kerinci. Almost half (40.7%) of them

work as farmers or engage in farming activities beside other jobs (Table 3). The environment at rural areas is mostly of farming

and animal husbandry with cool temperature, and located mostly at the mountainous area.

Table 3. Distribution of occupation
Occupation    Rural    %    Urban    %    Total    %
School dropouts
Employee
Self employed
Market vendors
Retiree
House works
Farmer
House works and farming
Employee and farming
Unemployed    1
0
5
0
0
0
13
5
6
4    1.7
0.0
8.5
0;0
0;0
0;0
22.0
8.5
10.2
6.8    0
9
1
2
4
4
0
0
0
5    0.0
15.2
1.7
3.4
6.8
6.8
0.0
0.0
0;0
8.5    1
9
6
2
4
4
13
5
6
9    1.7
15.1
20.2
3.4
6.8
6.8
22.0
8.5
10.2
15.1
Total    34    57.6    25     42.4    59    100.0

Almost half of patients (40.7%) were at stage I of PD, while about one third were in stage II (Table 4). Nineteen patients

(32.2%) looked for treatment before the symptoms lasts for one year or during stage I, while the longest time the suffering was

left untreated was 16 year (1.7%).(Table 5)  Regression analysis revealed a strong association(F.1,58=18,9; P=0,0006).

between stage of PD with the duration of untreated symptoms (Figure 1)

Table 4. Patient distribution according stage of PD at the time of first visit
Stage    Male     %    Female    %    Total    %
I    17    28.8    7    11.9    24    40.7
II    8    13.6    11    18.6    19    32.3
III    3    5.1    5    8.5    8    13.6
IV    2    3.4    4    6.8    6    10.2
V    0    0.0    2    3.4    2    3.4
Total    30
50.9    29
49.2
59    100.0

Table 5. Duration of untreated PD and stages of the disease.
Length of PD (yr)    Stage of disease    Total    %
I    II    III    IV    V
<1    12    5    2    –    –    19    32.2
1    6    2    1    2    –    11    18.6
2    2    4    2    –    –    8    13.5
3    2    2    –    1    –    5    8.4
4    –    2    –    –    –    2    3.3
5    –    1    2    –    –    3    5.1
6    2    1    –    1    –    4    6.7
8    –    –    1    –    1    2    3.3
10    –    –    –    1    –    1    1.6
11    –    1    –    –    1    2    3.3
13    –    1    –    –    –    1    1.6
16    –    –    –    1    –    1    1.6
Total    24    19    8    6    2    59    100.0

Figure 1. Regression analysis between duration of untreated PD and disease stages

There were 24 patients in stage I and eight patients in final stages (IV and V). For patients 45 years and older, two patients

were stage V (Table 6). Regression analysis (Figure 2) reveals a significant positive relationship between age and disease stages

(F 1,58 =11,115; P=0,0015).

Table 6. Relationship between age of first visit and stage of PD
Age    Stage of disease    Total    %
I    II    III    IV    V
15-24    3    1    –    –    –     4    6.8
25-34    1    –    1    –    –      2    3.4
35-44    1    –    –    –    –      1    1.7
45-54    8    2    –    1    –    11    18.6
55-64    6    12    4    2    –    24    40.7
65-74    4    4    1    1    1        11    8.6
75-84    –    –    2    2    1     5    8.5
85 +    1    –    –    –    –    1    1.7
Total    24    19    8    6    2    59    100.0

Figure 2. Regression analysis between age and disease stages

More than half of patients also suffered from some kind of comorbidities, in which hypertension is the most prevalent with 13

males (22.0%) and 16 females (27.1%) affected. Among them four males (6.8%) and one female (1.7%) also suffered form

stroke. Other accompanying diseases were diabetes mellitus, osteoarthritis, low back pain and rheumatism. Twenty five patients

(42.3%) did not have other disease, and the occurrence of this was the same between males and females (Table 7).

Table 7. Distribution of comorbidities among PD patients
Comorbidities    Male    Female    Total    %
Hypertension (Ht)
Ht + stroke
Ht + low back pain
Ht + hyperthyroidism
Ht + thoracic fracture
Diabetes mellitus
Osteoarthritis of knee
Low back pain
Rheumatism
None    9
4



1
1
2
1
12    11
1
2
1
1




13    20
5
2
1
1
1
1
2
1
25    33.8
8.5
3.4
1.7
1.7
1.7
1.7
3.4
1.7
42.3
Total    30    29    59    100.0

Occupation of eight patients suffered from late stage (IV and V) of PD includes farming, retired or unemployed. Most of the

occupations of eight stage III patients also include farming (Table 8). One of the patients died at the end of the research period.

Table 8. Distribution of occupation according to disease stages
Occupation    Stage of disease    Total
I    II    III    IV    V
Student    1    –    –    –    –    1
Office worker    5    3    1    –    –    9
Business    2    –    –    –    –    2
Street vendors    4    2    –    –    –    6
Retiree    –    3    –    1    –    4
House works    3    1    –    –    –    4
Farming     5    4    2    2    –    13
House work and farming    –    2    2    1    –    5
Office wok and farming    2    3    1    –    –    6
Unemployed    2    1    2    2    2    9
Total    24    19    8    6    2    59

Discussion
In this study we found 59 patients with PD, 30 of them are males, resulting in a male: female ratio of 1.03:1 (Table 1). Higher

ratios for males have also been reported by other workers. A ratio of 3 to 2 was reported by Waters (1999), 3.2 to 1 by Al

Bunyan (2001), and 3.04 to 1 by Bharucha et al. (1988). Al Bunyan reported his findings in Saudi Arabia during 1985 to 1997

on patients aged from 60 to 89 years old (3, 8) and Bharucha reported the ratio in Bombay, India, with patients only found

above 50 years old.
Marttila (1987) reported higher gross prevalence rate of PD for white population. In Finland the prevalence was 120 and the

incidence was 14.8 per 100,000; while in England (1961) he found the prevalence of 112 and the incidence of 12.2. For black

population in Baltimore (1969) the prevalence was only 31 for males and 4 for females, an even lower number. Further, in

Japan (1980) the prevalence was 81 with incidence 10.2, while in China (1983) the prevalence was 44. In 2001, Chen

conducted a survey in Taiwan which has the population of ethnic similarity with the mainland China, and reported the prevalence

of 130.1 and the incidence of 10.4. Chen also reported that no PD under was found under 40 years old, which is sharply

differed from Bower J.H et al in Minnesota, USA (1999) who reported the incidence of 0.8 per 100,000 in population 29

years old or younger (16). These results suggest that the environment is more important than race or ethnic factors in the

pathogenesis of PD (15). Our report that six patients out of 59 (10.2%) are under 34 years old also supports the suggestion

(Table 2).
Sutcliffe (1992) reported an increase of PD prevalence in Northampton, England from 108 per 100.000 in 1982, to 121 with

an incidence of 12 per 100,000 in 1992. He used Hoehn & Yahr method in establishing the diagnosis reinforced by symptoms

of micrograhic writings, and good response to treatment. Within 10 years, however, patients showed up with an increase in

physical disability (17)
Estimating risk ratio for PD in a population requires accurate incidence rate and vital statistics of that population. For example, if

1200 cases of PD were found within a lifetime in a population of 100,000, life-time risk for that population to acquire PD is

1.2%.
There are eight counties in West Sumatera with total farming area of about 22,563.47 sq.km, with 17 mountains and hills. The

majority (75.2%) of its 4,473,300 people live in rural areas (18). We found 24 (40.1%) patients with PD in our study who

works as farmers, whom comprise the majority of 34 patients (57.6%) from rural areas (Table 3). Thirteen of these farmers

came from the area of Pesisir Selatan and Kerinci, who work as rice farmers and coffee, cassia vera, gum and other plantations.

Most of the rural areas have cool temperatures, and the farmers mostly use fertilizers with nitrogen, phosphates, sulfur, P2O2,

and calcium. They also use pesticides, herbicides, or fungicides without hand gloves or maskers.
Hornykiewiecz (19) in 1989 pointed that the destruction of substantia nigra may be due to several causes such as infection,

toxins, and work environment using pesticide, herbicides, and carbon disulfite which is analogous with the chemical N-methyl-4

-phenyl 1,2,36-tetrahydropyridine (MPTP). There are also reports suggesting that different types of neurotoxins also play a part

in the neurodegeneration process of PD.
Some experts also suggest that MPTP has selective toxicity on substantia nigra and locus caeruleus, which precipitates a

parkinson-like syndrome in men. It is yet to be seen how the reduction of dopamine in the striatum results in tremor, rigidity, and

bradykinesia in these cases. Animals receiving this toxic substance have been shown to produce clinical symptoms and

pathological effects similar to PD (5,6,19).
Zhang reported in 1990 his study in Guam regarding factors related with PD, such as geographic, socio-economics, heavy metal

exposure, genetics, etc. He reported that indigenous people of Guam who live in rural areas have more prevalent cases of PD

compared to urban people. Native people are used to drink water from well, and in their bodies were found geochemical

substances such as iron, manganese, nitrogen and other chemicals. In their men the concentration of trace elements is higher. He

concluded his findings with the statement that the high risk for PD is associated with lower socioeconomic levels as indicated by

income, education level and family size, especially for men (20).
Some experts have forwarded a multifactor hypothesis as a cause of PD, comprise of chronic intoxication due to exposure to

chemicals in soil water, heavy metals such as mercury and zinc, and contact with certain toxic chemicals (19,20,21). Al Bunyan

also proposed a proof (albeit indirectly) of inadequacy of detoxification in the body of PD patients against free radicals and

toxins, which results in the continuation of neuronal damage. He suggested the use of antioxidants to reduce this progression (8).

Multivitamin consumption, especially vitamin E has been suggested to reduce the risk for PD development, as well as cessation

of smoking (7,22).
In this study we also report two siblings and their mother as having PD. This is consistent with Maher (2002) who reported that

the risk of PD suffering in siblings is high, especially if combined with genetic factors (22). Some studies have reported higher

incidence of PD in twins, in which one out 43 monozygotic twins have PD. Studies on monozygotic twins is the best method of

studying the influence of hereditary factors. In this study it seems that the cause of PD is not just hereditary, but also

environmental. Another case-control study showed that the sibling of PD sufferer may have a higher risk of having PD

compared to cousins. This means that this factor coupled with environmental exposure to toxic substances would increase the

risk of PD (9).
PD may not be the direct cause of death, which means that it may not be listed in the certificate of death. In general, mortality

rate is reported at a higher rate in America and Northern Europe. This rate seems to increase with age, with sharp increase

occurs at 60 years and beyond. Treatment of this disease has pushed the average age at death from 67-69 years to 72-73

years old, but also increase the length of suffering from 9-10 years to 13-14 years. Compared to non sufferers, relative life

expectancy for PD patients is around 67%. Hoehn & Yahr reported the death rate of PD patients of the same race, sex and age

as 2.9% higher compared to non sufferers. Treatment with levodopa seemed to improve the quality of life (9).
Another weakness in the reporting mortality rate of PD is the existence of comorbidities, which might be the main cause of death

itself. Chen reported the mortality rate of 40.4% for a population he followed for seven years. Relative risk of death is 3.38%

higher for patients with PD, with cumulative life expectancy 78.5% compared to 92.8% for non sufferers (15). In this study we

found that hypertension is the most prevalent comorbidities (33.8%), followed by stroke (8.5%) and others such as joint pain,

low back pain, and rheumatism which worsen the already present bradykinesia. Almost half of patients (42.3%) were free of

comorbidities (Table 7).

Conclusion:

1.    PD occurs all over the world with a higher frequency in males and white population, but lower in Blacks, Chinese

and Japanese.
2.    The most affected age was 50-70 years, and increase at 70-79 years. The presence of risk factors is directly

related to the frequency of PD occurrence.
3.    Prevalence and incidence varied according to research geography, design and diagnostic criteria. Epidemiological

studies were conducted more frequently on Caucasians in Northern Europe and America. According to WHO, prevalence is

100 to 200 and incidence is 20, while crude death rates varies from 0.5 to 3.8; all per 100,000 of population.
4.    The risk to suffer from PD is higher for the sibling and twins, and the presence of hereditary factors.
5.    In West Sumatera male female ratio is 1.03 to 1 and the affected age group is 55-64 years old. However, 10.2% of

patients were under 34 years old.
6.    Almost half of PD sufferers in West Sumatera work as farmers, and the most prevalent comorbidity was

hypertension.
7.    PD patients in West Sumatera show a significant correlation between PD stage with the length of suffering and with

age.

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Discussion

3 thoughts on “Parkinson Disease In West Sumatera and Kerinci An Epidemiological Apprasial

  1. tau artine vo

    Posted by soeharmiekav45 | April 8, 2010, 1:54 am
  2. It’s an article about Dementia that is really good!! Thanks!
    I also have a blog about Dementia too. Come visit me sometimes^_^

    Dementia Symptoms

    Posted by NubHammaWab | April 23, 2010, 9:08 am

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