Sau-Ying Lum

Dose-dependent protective effect of coffee, tea, and smoking in Parkinson's disease: a study in ethnic Chinese

INTRODUCTION Few studies have examined the relationship of coffee and tea in Parkinsons disease (PD). The potential protective effect of coffee intake and risk of PD has not been studied in a Chinese population. There is a high prevalence of caffeine takers among Chinese in our population. OBJECTIVE We undertook a case control study to examine the relationship between coffee and tea drinking, cigarette smoking, and other enviromental factors and risk of PD among ethnic Chinese in our population. METHODS AND RESULTS 300 PD and 500 population controls were initially screened. Two hundred case control pairs matched for age, gender, and race were finally included in the analysis. Univariate analysis revealed significant association of PD with coffee drinking (p<0.0005), tea drinking (p=0.019), alcohol drinking (p=0.001), cigarette smoking (p<0.0005), and exposure to heavy metals (p=0.006). Conditional logistic regression analysis demonstrated that amount of coffee drunk (OR 0.787, 95%CI 0.664-0.932, p=0.006), amount of tea drunk (OR 0.724, 95%CI 0.559-0.937, p=0.014), number of cigarettes smoked (OR 0.384, 95%CI 0.204-0.722, p=0.003), history of heavy metal and toxin exposure (OR 11.837, 95%CI 1.075-130.366, p=0.044), and heart disease (OR 5.518, 95%CI 1.377-22.116, p=0.016) to be significant factors associated with PD. One unit of coffee and tea (3 cups/day for 10 years) would lead to a 22% and 28% risk reduction of PD. One unit of cigarette smoke (3 packs/day for 10 years) reduced the risk of PD by 62%. CONCLUSIONS We demonstrated a dose-dependent protective effect of PD in coffee and tea drinkers and smokers in an ethnic Chinese population. A history of exposure to heavy metals increased the risk of PD, supporting the multifactorial etiologies of the disease.

Evidence of increased odds of essential tremor in Parkinson's disease

In a case control study using a standardized protocol, 600 subjects were evaluated for essential tremor (ET). We demonstrated that ET was significantly more frequent in patients with Parkinsons disease (PD) (12/204, 5.9%) compared to diseased controls (2/206, 1%) and healthy controls (1/190, 0.5%). A regression analysis with ET as outcome and group (either PD or healthy controls or diseased controls) as independent variable (adjusting for age and sex) revealed that PD had higher odds of having ET than diseased controls (OR = 5.43, 95% CI = 1.16, 25.39, P < 0.001) and healthy controls (OR = 10.87, 95% CI = 1.39, 85.15, P < 0.001). The low frequency of ET in our controls was further confirmed in a follow‐up study in a group of age and gender matched general medical patients who attended an outpatient clinic (0% frequency). Eight of 204 PD (3.9%) compared to none of diseased (0%) (P = 0.004) and healthy controls (0%) (P = 0.008) had a prior diagnosis of ET. The duration of ET symptoms in patients with PD was 25.1 ± 19.6 (range 3–60) years. A multivariate analysis demonstrated that a lower dose of levodopa (OR = 0.993, 95%CI for OR = 0.988, 0.997, P < 0.001) and a higher age of onset of disease (OR = 1.108, 95%CI for OR = 1.035, 1.187, P < 0.001) were associated with increased odds of PD with ET, compared to patients with PD without ET. In our Asian population, patients with PD were 5 to 10 times more likely to have ET compared to diseased and healthy controls, suggesting that the association of ET and PD is unlikely to be ethnicity‐specific.

Alpha synuclein promoter and risk of Parkinson's disease: microsatellite and allelic size variability.

Polymorphism of the alpha synuclein promoter region (non-amyloid component of plaques (NACP)-Rep1) is associated with an increased risk of Parkinsons disease (PD) in three separate studies. We studied NACP-Rep1 polymorphism in two independent case control studies in our population. In study one, 104 PD and 104 age, gender and race matched controls; and in study two, 102 PD and 102 age, gender and race matched controls were examined separately. The results of both studies were analyzed independent of one another. We found three polymorphic alleles (designated 0, 1, 2). In study one, the frequency of allele 2 was significantly higher in PD patients as compared to healthy controls (0.37 versus 0.23, P=0.01, X(2)=9.98). In study two, the frequency of allele 2 was similar between PD and controls (0.31 versus 0.33, P=1.00, X(2)=0.30). There was a non-significant higher allele 2 frequency in PD when both studies were analyzed together (0.34 versus 0.28, P=0.20, X(2)=3.4). No significant differences of the various genotypes between PD and controls were found. However there were differences of the mixed dinucleotide repeats sequences for similar homozygous genotypes. Variability of the microsatellite region and potential interacting factors that could affect alpha synuclein gene transcription should be further examined.

Validation of a short disease specific quality of life scale for hemifacial spasm: correlation with SF-36

Background: A short, practical, and validated quality of life (QoL) scale for hemifacial spasm (HFS) is not currently available. Objectives: To examine the reliability and validity of a short self-rating scale (HFS-7) by comparing HFS patients with healthy controls. We also evaluated the correlation of HFS-7 with the physical and mental domains of SF-36, a generic QoL scale. Methods: Seven self-rating items (HFS-7) were administered to HFS patients and healthy controls. In addition, HFS patients answered the SF-36 questionnaire. The validity and reliability of HFS-7 were analysed and correlation between HFS-7 and SF-36 examined. Results: A total of 178 subjects were enrolled in the study, including 85 HFS patients with mean age of 54.8 (SD 11.0) years, of whom 52 (61.2%) were women, and 93 controls with mean age of 51.4 (SD 10.0) years, of whom 59 (63.4%) were women. The test-retest intraclass correlation coefficient for the seven items was between 0.75 and 0.90 and Cronbach’s coefficient of reliability for the HFS-7 scale was 0.88. Every item in HFS-7 discriminated between disease and controls (p<0.0001). The HFS-7 summary index correlated with the SF-36 summary score (Spearman’s correlation r = −0.28, p = 0.009), in particular the mental health summary score (r = −0.416, p<0.0001) and the emotional domain (r = −0.466, p<0.00001). Conclusion: HFS-7 could prove useful as a simple clinical tool to assess and monitor QoL measures in HFS patients.

Monoamine oxidase B polymorphism, cigarette smoking and risk of Parkinson's disease: a study in an Asian population.

Cigarette smoking is associated with reduced monoamine oxidase B (MAO B) activity. Polymorphisms of the MAO B gene may modify the relationship between smoking and Parkinsons Disease (PD). We examined the association of MAO B intron 13 G/A polymorphism and risk of PD, and the modulation of the polymorphism on smoking and PD in an Asian study population in Singapore. Two hundred and thirty PD patients (mean age 66.0 ± 9.4 years, 63% men) and 241 age, gender, and race matched controls (mean age 64 ± 9.2 years, 58.9% males) were studied. The frequency of G and A alleles in PD and controls was; 66/315 (21.0%) vs. 73/340 (21.5%) and 249/315 (79.0%) vs. 267/340 (78.5%). For women, the genotype frequency in PD and controls was; GG: 7/85 (8.2%) vs. 8/99 (8.1%); GA: 25/85 (29.4%) vs. 27/99 (27.3%); AA: 53/85 (62.4%) vs. 64/99 (64.6%). For men, allele frequency in PD and controls was; A: 118/145 (81.4%) vs. 112/142 (78.9%) and G: 27/145 (18.6%) vs. 30/142 (21.1%). The allele and genotype frequencies were not significantly different between young and late onset PD. The frequency of “ever” smokers in PD and controls was 31/230 (13.5%) vs. 52/241 (21.6%), P = 0.02. A stepwise logistic regression analysis did not reveal any interaction of smoking and the G allele and risk of PD. The MAO B G/A genotype frequency in our Asian population was quite different from Caucasians suggesting that ethnicity specific effects need to be considered in evaluating gene‐environmental interaction.

Dopamine D2 receptor TaqIA and TaqIB polymorphisms in Parkinson's disease

In a case control study, we examined the association of DRD2 Taq1A and Taq1B polymorphisms and risk of PD, and evaluated the strength of linkage disequilibrium of the polymorphisms. The Taq1A and Taq1B polymorphisms were in strong linkage disequilibrium. There was, however, no significant association of the two polymorphisms with PD.

Clinical features of childhood onset essential tremor

Childhood onset essential tremor (ET) is uncommon. It is not clear as to whether ethnicity‐specific differences may influence the phenotypic features. To determine the frequency and clinical characteristics of childhood ET in a tertiary referral center. In a prospective evaluation of 120 consecutive ET patients in a movement disorders clinic, we found a 15.5% (19) frequency of childhood onset ET patients. The mean age of onset and mean age was 10.8 ± 4.1 (6–16) years and 25.7 ± 15.0 (16–73) years consisting of 73.6% (14/19) men and 26.4% (5/19) women. A positive family history of ET was present in 11 of 19 (52.6%). Presence of a head tremor was observed in 2/19 (10.5%). We highlighted a relatively high frequency (15,5%) of childhood ET in our Asian cohort. In addition, we drew attention to the male preponderance and the low frequency of head tremor in childhood ET corroborating study findings in white ET patients. These observations appear to transcend ethnic and cultural differences and lend further support that gender difference may play a role in the pathogenesis and expression of ET.

Functional COMT variant predicts response to high dose pyridoxine in Parkinson's disease

Pyridoxal‐5‐phosphate, the biological active form of pyridoxine, is a cofactor for dopa‐decarboxylase (DDC) enzyme. Pyridoxine may augment the conversion of levodopa to dopamine in the periphery and therefore decrease availability of levodopa to the brain. However, this effect can be negated in the presence of a DDC inhibitor, which potentiates plasma levodopa level. A single nucleotide polymorphism at the nucleotide 1947 in the catechol‐O‐methyltransferase (COMT) gene encodes the high (COMTH) and low activity (COMTL) forms of the enzyme. In this study, we examined the effect of the COMTL allele on the clinical response to pyridoxine in Parkinsons disease (PD) patients. PD patients who were on stable and optimized dose of levodopa were included in this study. Their mean motor and activities of living score improved after high dose pyridoxine (P = 0.09, P = 0.04), and worsened after a washout period (P = 0.005, P = 0.001). Using a multivariate model, the presence of the COMTL allele predicted response to pyridoxine, with the best outcome observed in COMTL/L homozygotes. Our observational study suggests that the status the functional COMTL variant may be potentially useful to select PD patients for high dose pyridoxine therapy.

Treatment outcome correlates with knowledge of disease in hemifacial spasm.

OBJECTIVES Hemifacial spasm (HFS), a potentially disabling facial condition affects quality of life (QOL) and botulinum toxin is an effective treatment. No studies have examined whether a better level of knowledge of the disease would lead to an improved quality of life and treatment response in HFS. We examined the relationship between knowledge of disease with improvement in QOL following botulinum toxin treatment in HFS patients. PATIENTS AND METHODS A total of 106 HFS patients (mean age of 56.8+/-9.9 years) were prospectively included. A baseline knowledge questionnaire and a validated disease-specific quality of life scale (HFS-7) were administered before and after botulinum toxin treatment. RESULTS A better educational level was an independent predictor of high knowledge of HFS (p=0.02). Multivariate analysis using improvement in HFS-7 (total and subscore) as outcomes, and adjusting for age, gender, education, severity and duration of HFS, showed that high knowledge was predictive of a bigger improvement in HFS-7 total (p=0.03) and HFS-7 subscore (p=0.03). CONCLUSIONS HFS patients with high knowledge of disease reported better improvement in QOL following botulinum toxin treatment. Better educational efforts will augment current medical and surgical treatments in improving QOL in HFS. Our findings could potentially be extended to many other medical conditions.

Clinical correlates of phosphene perception in migraine without aura: An Asian study

INTRODUCTION Although controversy exists with regard to the presence of hypoexcitability versus hyperexcitability of the visual cortex in migraine patients, there remain a group who do not perceive phosphenes (P-). However, its clinical implications have not been systematically addressed. In this study, we hypothesize that P- patients classified as migraine without aura (MO) have distinct clinical features. METHODS Twenty-nine Asian MO patients (7 men; mean age: 44; median: 45; range: 25 to 65) were consecutively entered into the study. Visual cortex transcranial magnetic stimulation (TMS) was performed in the migraine interictum. RESULTS Of the 19 patients, 19 (66%) were able to perceive phosphenes (P+), while 10 (34%) were not able to after repeated TMS (P-). P- patients had significantly higher headache frequency (p=0.008) and pain score (p=0.002) compared with P+ patients. In addition, there was significant positive correlation of phosphene threshold with pain score (r=0.52, p=0.02) in P+ patients. There was no significant difference between P+ and P- patients in terms of age (t-test, p=0.6). CONCLUSIONS Our study is inkeeping with the hypothesis that interictal visual cortex excitability is reduced in relation to the severity of migraine in Asian MO patients, and lack of phosphene perception may be related to significantly elevated thresholds beyond the output of TMS stimulators.