Yang-Chyuan Chang

Environmental risk factors and Parkinson's disease A case‐control study in Taiwan

To explore environmental risk factors for Parkinsons disease (PD) in Taiwan, we investigated 120 patients with PD and 240 hospital control subjects matched with patients on age (± 2 years) and sex. Based on a structured open-ended questionnaire, we carried out standardized interviews to obtain history of exposure to environmental factors, including place of residence, source of drinking water, and environmental and occupational exposures to various agricultural chemicals. In the univariate analysis, the history of living in a rural environment, farming, use of herbicides/pesticides, and use of paraquat were associated with an increased PD risk in a dose-response relationship. After adjustment for multiple risk factors through conditional logistic regression, the biological gradient between PD and previous uses of herbicidesipesticides and paraquat remained significant. The PD risk was greater among subjects who had used paraquat and other herbicide/pesticides than those who had used herbicides/pesticides other than paraquat. There were no significant differences in occupational exposures to chemicals, heavy metals, and minerals between PD patients and matched control subjects. The duration of drinking well water and alcohol consumption was not significantly associated with PD. There was an inverse relationship between cigarette smoking and PD. Environmental factors, especially exposures to paraquat and herbicides/pesticides, may play important roles in the development of PD in Taiwan.

Subtypes of Ischemic Stroke: A Hospital-Based Stroke Registry in Taiwan (SCAN-IV)

BACKGROUND AND PURPOSE To better understand the clinical pattern and further elucidate the risk factors and outcome in different subtypes of cerebral infarction (CI) of the Chinese in Taiwan, we analyzed the National Taiwan University Hospital Stroke Registry in 1995 and performed an ethnic comparison with similar data banks. METHODS From the National Taiwan University Hospital Stroke Registry in 1995, 676 patients (383 men and 293 women; mean age, 64.9 years; SD, 13.8 years; range, 1 to 98 years) with CI were recruited for this analysis. CI was classified into five subtypes based on clinical manifestations, ultrasonographic studies, and neuroimaging findings: large-artery atherosclerosis, lacunae, cardioembolism, other less common determined causes, and undetermined cause. Vascular risk factors, extracranial carotid artery atherosclerosis, and 30-day case-fatality rates were investigated in each subtype of CI. RESULTS Of all CI patients, 17%, 29%, 20%, 6%, and 29% were classified as large-artery atherosclerosis, lacunae, cardioembolism, other determined causes, and undetermined cause subtypes, respectively. The present results were compared with those from eight similar Western stroke registries. The relative incidence of lacunar CI in Chinese patients was more common, but large-artery atherosclerotic CI was less common than in whites. Hypertension was frequently seen in CI patients, especially in those with lacunae (85%) and large-artery atherosclerosis (69%). Patients with cardioembolism had a higher percentage of atrial fibrillation (69%), left ventricular hypertrophy, and ischemic heart disease than the other patients. Patients with large-artery atherosclerosis had more vascular risk factors, such as hypertension, diabetes mellitus, smoking, and carotid stenosis. Cardioembolic patients had higher case-fatality rates than other CI patients. Of the cardioembolic patients, 17.3% and 21.8% died within 30 days and during hospitalization, respectively. CONCLUSIONS The proportion of CI subtypes varied in different stroke registries. This may be partly due to applied classification criteria and racial-ethnic differences. Awareness of the risk factors and outcome in each subtype of stroke may afford further insights into the surveillance and treatment of cerebrovascular disease.

Influence of aging on thermal and vibratory thresholds of quantitative sensory testing

Abstract  Quantitative sensory testing has become a common approach to evaluate thermal and vibratory thresholds in various types of neuropathies. To understand the effect of aging on sensory perception, we measured warm, cold, and vibratory thresholds by performing quantitative sensory testing on a population of 484 normal subjects (175 males and 309 females), aged 48.61 ± 14.10 (range 20–86) years. Sensory thresholds of the hand and foot were measured with two algorithms: the method of limits (Limits) and the method of level (Level). Thresholds measured by Limits are reaction‐time‐dependent, while those measured by Level are independent of reaction time. In addition, we explored (1) the correlations of thresholds between these two algorithms, (2) the effect of age on differences in thresholds between algorithms, and (3) differences in sensory thresholds between the two test sites. Age was consistently and significantly correlated with sensory thresholds of all tested modalities measured by both algorithms on multivariate regression analysis compared with other factors, including gender, body height, body weight, and body mass index. When thresholds were plotted against age, slopes differed between sensory thresholds of the hand and those of the foot: for the foot, slopes were steeper compared with those for the hand for each sensory modality. Sensory thresholds of both test sites measured by Level were highly correlated with those measured by Limits, and thresholds measured by Limits were higher than those measured by Level. Differences in sensory thresholds between the two algorithms were also correlated with age: thresholds of the foot were higher than those of the hand for each sensory modality. This difference in thresholds (measured with both Level and Limits) between the hand and foot was also correlated with age. These findings suggest that age is the most significant factor in determining sensory thresholds compared with the other factors of gender and anthropometric parameters, and this provides a foundation for investigating the neurobiologic significance of aging on the processing of sensory stimuli.

Patterns of contact heat evoked potentials (CHEP) in neuropathy with skin denervation: Correlation of CHEP amplitude with intraepidermal nerve fiber density

OBJECTIVE Contact heat evoked potentials (CHEPs) provide an objective approach to investigate cerebral responses to thermal stimuli mediated by Adelta fibers. Skin denervation is often associated with reduced thermal sensibilities. We aimed to investigate the influences of skin denervation on CHEPs in neuropathic patients. METHODS CHEPs were recorded at the vertex area by applying contact heat stimuli of 51 degrees C on the distal leg of neuropathic patients with sensory symptoms and pathological evidence of skin denervation in the distal leg. Patterns and parameters of CHEPs in the neuropathic group were compared with those in the control group of age- and gender-matched subjects. RESULTS There were 25 neuropathic patients with reduced intraepidermal fiber (IENF) density (1.46+/-1.70fibers/mm, range: 0-5.32). In the control group, well-defined averaged tracings of CHEPs with an initial negative peak (N-wave) followed by a positive peak (P-wave) were consistently recorded in all 25 subjects. The peripheral conduction velocities of CHEPs were 9.92+/-4.06m/s (range: 6.06-16.60), in the range of Adelta fibers. The group of neuropathic patients had markedly reduced N-P amplitudes (p<0.0001) and prolonged N-wave latencies (p=0.049) compared to the control group. IENF density was the only neuropathic parameter correlated with N-P amplitude on multiple linear regression analysis (p=0.010) compared to large-fiber parameters. CONCLUSIONS In neuropathic patients with pathological evidence of skin denervation, there were reduced amplitude and prolonged latencies in CHEPs mediated by Adelta fibers. The reduction of CHEP amplitude corresponded to the degree of skin denervation. SIGNIFICANCE CHEP offers electrophysiological evidence of thermal responses and provides an objective, non-invasive approach to assess the physiological counterparts of skin denervation in neuropathic patients.

Extracranial carotid atherosclerosis and vascular risk factors in different types of ischemic stroke in Taiwan.

The clinical patterns of stroke and the angiographic distribution of cerebral atherosclerosis in Chinese people are different from those in whites. Studies relating carotid atherosclerosis and vascular risk factors to various types of stroke in Chinese people are lacking. Methods Based on clinical information, we separated 367 stroke patients living in Taiwan into four subgroups: cortical infarction (CI), subcortical infarction (SCI), vertebrobasilar artery infarction (VBAI), and cardioembolic infarction (CEI). We assessed the extent and severity of extracranial carotid artery atherosclerosis in different types of ischemic stroke using duplex ultrasonography. Vascular risk factors and carotid atherosclerosis were then correlated with each subgroup of ischemic stroke. Results Our data revealed that 32% of the CI subgroup, 3% of the SCI subgroup, 7% of the VBAI subgroup, and 21% of the CEI subgroup possessed severe carotid stenosis (≥50% stenosis or occlusion). The extent of atherosclerosis of extracranial carotid arteries, measured by plaque score, was also more severe in the CI subgroup than in the other subgroups. Diabetes mellitus was more frequent in the CI subgroup. Cardiomegaly and left ventricular hypertrophy were more commonly seen in the CEI subgroup. The VBAI subgroup was younger than the other subgroups. There were no differences in hypertension, prior stroke, alcohol intake, or serum levels of glucose, uric acid, hematocrit, lipids, and lipoproteins among the subgroups. Conclusions Of the Chinese patients living in Taiwan, the extent and severity of extracranial carotid artery atherosclerosis were more prominent in patients with CI than in patients with other types of ischemic stroke. In Chinese patients with CI, severe carotid stenosis is not uncommon; in Chinese patients with SCI, however, the frequency of carotid stenosis is quite low.

Effects of aging on human skin innervation

To understand the effect of aging on human skin innervation, we investigated intraepidermal nerve fiber (IENF) density of skin biopsies. IENF densities of the distal leg were lower in elderly (≥ 60 years of age) than in young adults (19–39 years of age; 7.80 ± 0.79 vs 13.55 ± 0.85 fibers/mm, p < 0.01). A similar trend was also observed in the distal forearm (11.67 ± 1.55 vs 19.39 ± 1.60 fibers/mm, p < 0.001). IENF densities were negatively correlated with age according to multiple linear regression analysis on the entire study population (age range: 19–78 years) with standardized coefficients of −0.462 (p < 0.001) in the distal leg and −0.335 (p = 0.005) in the distal forearm. These findings suggest a significant reduction in IENF densities with age.

Effects of aging on contact heat-evoked potentials: The physiological assessment of thermal perception

Age significantly influences the detection thresholds to noxious heat; such thresholds depend on responses in the cerebral cortex to thermal stimuli and the psychophysical perception of such responses. To understand the influence of age on cerebral responses, we used contact heat‐evoked potentials (CHEPs) to investigate the physiology of cerebral responses to thermal stimuli in 70 healthy subjects (33 men and 37 women, 39.56 ± 12.12 years of age). With heat stimulation of fixed intensity (51°C) on the distal forearm and distal leg, CHEPs revealed consistent waveforms with an initial negative peak (N1 latency: 398.63 ± 28.55 and 449.03 ± 32.21 ms for upper and lower limbs) and a later positive peak (P1 latency: 541.63 ± 37.92 and 595.41 ± 39.24 ms for upper and lower limbs) with N1–P1 interpeak amplitude of 42.30 ± 12.57 μV in the upper limb and 39.67 ± 12.03 μV in the lower limb. On analyses with models of multiple linear regression, N1–P1 amplitudes were negatively correlated with age and N1 latencies were correlated with gender, with females having shorter latencies. The verbal rating scale (VRS) for pain perception was higher in females than males, and decreased with aging. In addition, VRS paralleled changes in N1–P1 amplitude and N1 latency; the higher the VRS, the shorter the N1 latency and the higher the N1–P1 amplitude. These results provide evidence that CHEPs are influenced significantly by aging, corresponding to aging‐related changes in thermal pain perception. Muscle Nerve, 2007

Pathophysiology of Neuropathic Pain in Type 2 Diabetes: Skin denervation and contact heat–evoked potentials

OBJECTIVE Neuropathic pain due to small-fiber sensory neuropathy in type 2 diabetes can be diagnosed by skin biopsy with quantification of intra-epidermal nerve fiber (IENF) density. There is, however, a lack of noninvasive physiological assessment. Contact heat–evoked potential (CHEP) is a newly developed approach to record cerebral responses of Aδ fiber–mediated thermonociceptive stimuli. We investigated the diagnostic role of CHEP. RESEARCH DESIGN AND METHODS From 2006 to 2009, there were 32 type 2 diabetic patients (20 males and 12 females, aged 51.63 ± 10.93 years) with skin denervation and neuropathic pain. CHEPs were recorded with heat stimulations at the distal leg, where skin biopsy was performed. RESULTS CHEP amplitude was reduced in patients compared with age- and sex-matched control subjects (14.8 ± 15.6 vs. 33.7 ± 10.1 μV, P < 0.001). Abnormal CHEP patterns (reduced amplitude or prolonged latency) were noted in 81.3% of these patients. The CHEP amplitude was the most significant parameter correlated with IENF density (P = 0.003) and pain perception to contact heat stimuli (P = 0.019) on multiple linear regression models. An excitability index was derived by calculating the ratio of the CHEP amplitude over the IENF density. This excitability index was higher in diabetic patients than in control subjects (P = 0.023), indicating enhanced brain activities in neuropathic pain. Among different neuropathic pain symptoms, the subgroup with evoked pain had higher CHEP amplitudes than the subgroup without evoked pain (P = 0.011). CONCLUSIONS CHEP offers a noninvasive approach to evaluate the degeneration of thermonociceptive nerves in diabetic neuropathy by providing physiological correlates of skin denervation and neuropathic pain.

Chromobacterium violaceum infection in children: a case of fatal septicemia with nasopharyngeal abscess and literature review.

This previously healthy 5-year-old boy initially presented with fever and purulent conjunctivitis. The course evolved rapidly into preseptal and facial cellulitis, nasopharyngeal abscess and sepsis. Chromobacterium violaceum was isolated from conjunctival exudate and blood cultures. He received intravenous cefazolin therapy for 2 days, followed by penicillin, oxacillin and netilmicin. However, no improvement was noted, and he died on the fifth days of illness.

Painful neuropathy with skin denervation after prolonged use of linezolid

The prolonged use of linezolid, a new antibiotic against drug-resistant Gram-positive pathogens, might cause painful neuropathy. This finding raises the possibility that small-diameter sensory nerves in the skin, which are responsible for transmitting nociceptive information, might be affected. We report a 53-year-old female who developed pure small-fibre painful neuropathy (visual analogue scale, VAS = 82 on 0–100 scale) with marked skin denervation in the leg (epidermal nerve density, END = 2.32 fibres/mm, norm <5.88 fibres/mm) and significant elevation of the warm threshold in the foot (40.0°C, norm <39.4°C) after the use of linezolid for 6 months. Eight months after the discontinuation of linezolid, the skin became fully reinnervated (END = 9.04 fibres/mm), with disappearance of neuropathic pain (VAS = 0) and normalisation of the warm threshold (36.3°C). Nerve conduction studies for large-diameter motor and sensory nerves were normal. This report documents a pure small-fibre sensory neuropathy after prolonged use of linezolid, and the relationship between skin innervation and corresponding neuropathic pain.