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In our previous studies, photobiomodulation (PBM) stimulation can induce significant brain activation in normal subjects. In an open-eye study, the PBM stimulation was able to increase the power of alpha rhythms and theta waves, as well as decrease the beta activities after PBM stimulation. However, in the closed eyes study, the alpha rhythms in the laser group were reduced. This means the PBM stimulation can induce specific brainwaves under different conditions. Thus, to investigate the effects of PBM stimulation on human’s attention, forty students were recruited in this single-blind randomized trial. A PBM stimulator, with seven pcs laser diodes (LDs), frequency 10 Hz, 30 mW/each LD, and wavelength 830 nm, was used to radiate the palm of the subject. PBM stimulation was found to induce significant variation in beta activity in most of the regions of the brain in the laser group. Compared to the placebo group, the PBM stimulation has a significant change in beta activity on electroencephalography (EEG). Three types of tests, the random number test, the Stroop color-word test, and the Multiple-Dimension Attention Test (MDAT), were used to evaluate the effects of the PBM stimulation. The scores of MDAT in the laser group increased more significantly than those in the placebo group after PBM stimulation (p < 0.01). An improvement in attention was observed in this study.

To study the prognostic features of Creutzfeldt-Jakob disease (CJD) and shed light on its future therapy.Retrospective cohort study of a longitudinal national cohort of the Taiwan Centers for Disease Control.All patients with suspected CJD are reported to the CJD surveillance unit of the Taiwan Centers for Disease Control. An expert committee discussed the reported cases and designated a consensus-based diagnosis. From 1996 to 2020, a total of 809 cases were referred to the CJD surveillance unit for confirmation; of these, 441 cases (women, n = 230) were determined to be sporadic CJD.We investigated the clinical manifestations and laboratory findings for 400 patients diagnosed with definite or probable sporadic CJD. We used Kaplan-Meier analyses and Cox proportional hazards model to identify prognostic factors.The mean age of onset was 67 ± 9.9 years. The mean survival duration was 13.3 ± 14.2 (median 10) months. The leading clinical symptoms were myoclonus (73%) and akinetic mutism (54%). For PRNP polymorphism, 99% of patients (195/197) showed a methionine homozygous genotype at codon 129 (M129M). The sensitivity of periodic sharp wave complexes (PSWCs) on electroencephalograms (EEGs) was 59.7%. The sensitivity of cerebrospinal fluid 14-3-3 protein and total tau protein (1200 pg/mL) were 69.7% and 75.6%, respectively. Younger patients lived longer than those aged ≥65 years [hazard ratio (HR) 0.466, P.001]. Women had a better survival probability in the first 3 years than their male counterparts (HR 0.712, P = .005). PSWCs had a persistent negative effect on survival (HR 0.788, P.05). Although uncommon, epileptic seizures were the only clinical prognostic factor for survival time (HR 0.768, P.05). PSWCs can be used as an EEG biomarker for prognosis. Epileptic seizures, though not common, are the only clinical prognostic factor for a short survival.We found that a lower age of onset and female gender favor the survival of patients with sCJD. PSWCs are EEG biomarkers unfavorable for survival, and so are epileptic seizures.

Introduction Epidemiologic studies of Creutzfeldt-Jakob disease (CJD) have been undertaken worldwide since the new variant CJD outbreak in 1996 in the United Kingdom. A nationwide report system, the Creutzfeldt-Jakob Disease Surveillance Unit (CJDSU), directed by the Centers for Disease Control of Taiwan, was established in 1997 to identify human prion diseases. Methods From 1998 to 2017, 647 cases were referred to the committee for confirmation. The report to CJDSU included a structured questionnaire recording the clinical, demographic data, and potential iatrogenic exposure, and the results of the clinical and laboratory examination, including tests of blood and cerebrospinal fluid, electroencephalography, and brain magnetic resonance imaging. Results In total, 356 cases (women, n=178) were ascertained to be human prion diseases, and 97.4% (n=347) were sporadic CJD, including three definite, 314 probable, and 30 possible cases; one probable variant CJD and 8 cases of the genetic form human prion diseases. The age- and gender-specific average annual incidence were also significantly higher in the second decade (0.95/1,000,000) than in the first decade (0.63/1,000,000), with an incidence rate ratio of 1.51. The incidences increased with increasing age, reaching a peak at the age of 70-79 years. The 10-year survival curve for sCJD patients showed that the 1-, 5-, and 10-year cumulative survival rate were 52%, 5%, and 1%, respectively. PRNP polymorphisms in 170 patients showed that 98.8% were M129M and 97.6% E219E. Discussion The significant increase in incidence after 2008 suggests the increase in the awareness of this rare disease among physicians. The longer disease duration in patients with sCJD in Taiwan than in other countries indicates that the comprehensive support of the health care system, as well as the end-of-life care culture in Taiwan, may prolong survival time in patients with such a progressive and fatal disease.

In our previous study, the low-level laser (LLL) stimulation at the palm with a stimulation frequency of 10 Hz was able to induce significant brain activation in normal subjects. The electroencephalography (EEG) changes caused by the stimulation of light-emitting diode (LED) in normal subjects have not been investigated. This study aimed at identifying the effects of LED stimulation on the human brain using EEG analysis. Moreover, the dosage has been raised 4 times than that in the previous LLL study. The LED array stimulator (6 pcs LEDs, central wavelength 850 nm, output power 30 mW, and operating frequency 10 Hz) was used as the stimulation source. The LED stimulation was found to induce significant variation in alpha activity in the occipital, parietal, and temporal regions of the brain. Compared to the previous low-level laser study, LED has similar effects on EEG in alpha (8–12 Hz) activity. Theta (4–7 Hz) power significantly increased in the posterior head region of the brain. The effect lasted for at least 15 minutes after stimulation ceased. Conversely, beta (13–35 Hz) intensity in the right parietal area increased significantly, and a biphasic dose response has been observed in this study.

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 degrees 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 microV in the upper limb and 39.67 +/- 12.03 microV 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.

We studied the sensory evoked potentials in pediatric Wilson disease to verify their subclinical neurologic involvement and to elucidate the role of cirrhosis in abnormal evoked potentials in non-neurologic Wilson disease. Thirty children (17 male, 13 female), diagnosed with Wilson disease before 18 years, were enrolled. The mean age during studies was 15.8 ± 6.3 years, and disease duration since diagnosis was 3.0 ± 3.3 years. In 12 neurologic Wilson disease cases, there were prolonged interpeak latencies of brainstem auditory evoked potentials III-V, I-V, somatosensory evoked potentials N13-N20 (P < 0.01 vs controls and non-neurologic cases), and P100 latency (P < 0.01 vs controls). All 12 patients had at least one abnormal evoked potential, including 91.7% brainstem auditory, 58.3% somatosensory, and 25% visual evoked potentials. In 18 non-neurologic Wilson disease cases, there were still prolonged interpeak latencies for brainstem auditory evoked potentials I-V and somatosensory evoked potentials N13-N20 (P < 0.05 vs controls), with 27.8% of them having at least one abnormal evoked potential, including 16.6% brainstem auditory, 5.6% somatosensory, and 11.1% visual evoked potentials. In those with non-neurologic Wilson disease, there were no significant differences in all the evoked potential parameters between the cirrhotic and non-cirrhotic patients.

Sleep problems are getting worse and worse in modern world. They have a severe impact on psychological and physical health, as well as social performances. From our previous study, the brainwave α rhythm, θ wave and β wave were affected by radiating the palm of the subjects with low-level laser array. In addition, from other study, the LED array stimulator (LEDAS) also has the similar effects. In the present study, LED light was used to radiate the left palm of the subjects too, and the effects were assessed with the multiple sleep latency test (MSLT) and heart-rate variability (HRV) analysis. The results revealed that it doesn’t have significant meaning between these two groups. However, the tendency of the sleep latency (SL) in the LED group was shorter than that in the control group. In addition, the autonomic nervous system (ANS) analysis showed that the sympathetic nervous system was getting larger in the LED group than that in the control group, and total ANS activity were mainly getting larger in the LED group. We infer that this LED stimulation could reduce SL and balance ANS activity of the night-shift people. In the future, the further study will be conducted on normal subjects.

Pathological diagnosis of neuropathy has traditionally depended on ultrastructural examinations of nerve biopsy specimens, particularly for sensory neuropathies affecting unmyelinated and small-myelinated nociceptive nerves. These sensory nerves terminate in the epidermis of the skin, and the pathology of neuropathy usually begins from nerve terminals. We investigated the feasibility of diagnosing small-fiber sensory neuropathy by evaluating cutaneous innervation. Skin biopsy specimens of 3-mm in diameter were obtained from the distal leg and the distal forearm of 55 healthy controls and 35 patients with sensory neuropathy. In the healthy controls, conventional intraepidermal nerve fiber densities (IENF densities) as measured using the image analysis system in the distal forearm and in the distal leg were correlated (r=0.55, P0.0001), with significantly higher values in the distal forearm than in the distal leg (17.07+/-6.51 vs 12.92+/-5.33 fibers/mm, P0.001). Compared to IENF densities of healthy controls, these values of neuropathic patients were significantly reduced in the distal forearm (5.82+/-6.50 fibers/mm, P0.01) and in the distal leg (2.40+/-2.30, P0.001). We further explored the possibility of quantifying skin innervation by counting "ocular intraepidermal nerve fiber density" (ocular nerve fiber density) with no aid of an image analysis system. This was based on the fact that the epidermal length on specifically defined sections was very close to the predicted epidermal length of 3 mm, the diameter of skin punches (P=0.14). Ocular nerve fiber densities were significantly correlated with IENF densities as measured by the image analysis system (r=0.99, P0.0001). Dermal nerve fibers of neuropathic patients either disappeared or became degenerated. These findings were consistent with the notion of early terminal degeneration in neuropathy, and will facilitate quantitative interpretation of epidermal innervation in human neuropathy.

To analyse the effect of epilepsy an P300 event-related potentials we studied 27 patients with idiopathic generalized epilepsy (IGE), 13 patients with temporal lobe epilepsy (TLE) and 60 normal controls. The prolongation of P300 latencies was highly cor related with increasing age in controls but not epileptic patients. The age-corrected P300 latency used in this study was actual P300 latency–predicted P300 latency (predicted P300 (msec)=306.20+0.79 age, P =0.001, R 2 =0.32). By using ANOVA analysis, the age-corrected latencies of P300 were significantly longer in TLE patients (19.72±47.82 msec, mean±SD) than in IGE patients (10.97±36.97 msec) and controls (0.23±20.28 msec). Likewise, significantly prolonged P300 latencies were seen in the epileptic patients with a seizure frequency more than 400 times (37.21±47.50 msec). The multivariate-adjusted odds ratio for those who had TLE was 10.97 (95% CI=3.99 − 30.14 ) in the prolonged latencies of P300 compared with that of IGE patients. The odds ratio of longer latencies of P300 was 7.43 (95% CI=2.75 − 20.08) among those who had a high seizure frequency (≧400 times) compared with those who had a low seizure frequency. No interaction between TLE and high frequency of attacks was found. The age at onset of seizure and duration of illness was not associated with P300 latency prolongation. From the above results, we might infer that the seizure type of TLE and a high frequency of seizure are two major independent precipitate factors for abnormal latencies of P300 in the epileptic patients.

In a previous study, we found that the low-level laser (LLL) stimulation at the palm with a frequency of 10 Hz was able to induce significant brain activation in normal subjects with opened eyes. However, the electroencephalography (EEG) changes to LLL stimulation in subjects with closed eyes have not been studied. In the present study, the laser array stimulator was applied to deliver insensible laser stimulations to the palm of the tested subjects with closed eyes (the laser group). The EEG activities before, during, and after the laser stimulation were collected. The EEG amplitude powers of each EEG frequency band at 19 locations were calculated. These power data were then analyzed by SPSS software using repeated-measure ANOVAs and appropriate posthoc tests. We found a pronounced decrease in the EEG power in alpha-bandwidth during laser simulation and then less decrease in the EEG power in delta-bandwidth in normal subjects with laser stimulation. The EEG power in beta-bandwidth in the right occipital area also decreased significantly in the laser group. We suggest that LLL stimulation might be conducive to falling into sleep in patients with sleep problems.

Affecting the brainwave by radiating the palm of the tester with a low-level laser array has been proposed in our previous study. The power of alpha rhythms has been increased mainly in the posterior head regions. The effect lasted at least 15 minutes after cessation of the laser stimulation. However, the effect of non-coherent light (Light Emitting Diode, LED) in similar conditions hasn’t been investigated. In this study, a LED array stimulator (6 pcs LEDs, central wavelength 850nm, output power 30mW, operation frequency: 10 Hz) was designed to be the light source. An eyes-open EEG data were recorded during and after stimulation. The experimental results reveal the power of the alpha band has been enhanced with this LED array which operated in 10Hz. Significant activations were found in the parietal lobe、 the occipital lobe and the temporal lobe (p

Thrombosis of the thoracic inlet veins following placement of a central venous catheter is a well-known complication, and several findings have been reported by color Doppler sonography. However, reverse jugular flow resulting from this complication is rarely mentioned and should be differentiated from another complication of iatrogenic arteri ovenous fistula between neck vessels. The authors here describe a uremic patient with an artificial arteriovenous fistula in the forearm complicated with thrombosis of the ipsilat eral brachiocephalic vein. Factors permitting the differential diagnosis by color Doppler sonography and clinical conditions are proposed.

Skin innervation has been considered to subserve sensory perception only, but several lines of evidence suggest that there are "effector' influences of skin innervation on the immune system and keratotinocytes. In this study, we transected the sciatic nerves of rats and examined the effects of denervation on the epidermis. In normal skin, the epidermis was densely innervated by fine axons that were immunostained with several axonal markers, including neuronal ubiquitin carboxyl terminal hydrolase (protein gene product 9.5). All of the epidermal axons in the regions innervated by sciatic nerve disappeared within 24-48 h after transection of sciatic nerve, and remained absent as long as subsequent reinnervation by regenerating axonal sprouts was prevented. Denervation produced changes in both the keratinocytes and the Langerhans cells, the bone marrow-derived antigen-presenting cells of the epidermis. The thickness of epidermis decreased within 7 days. By 48 h after transection, the Langerhans cells and their dendritic processes became intensely immunoreactive for protein gene product. Protein gene product 9.5 expression on Langerhans cells remained prominent as long as skin was denervated, but disappeared with reinnervation. By reverse transcription-polymerase chain reaction, we demonstrated the presence of the transcripts for protein gene product 9.5 in epidermis, consistent with the synthesis of the protein by the Langerhans cells. We conclude that epidermal sensory fibres have novel influences on both keratinocytes and Langerhans cells of the epidermis.

A survey of public awareness and understanding of and attitudes toward epilepsy was made in Taipei City and Chin-San Village, Taiwan in 1992. In a population sample of 2,610 adults, 87% had read or heard about epilepsy, 70% knew someone who had epilepsy, 56% had seen someone having a seizure, 18% would object to having their children associated with persons with epilepsy, 72% would object to having their children marry a person with epilepsy, 31% believed that epileptic persons should not be employed in jobs as other persons are, 7% believed that epilepsy was a form of insanity, 34% did not know the cause of epilepsy, 13% did not know what an epileptic attack was like, and 18% did not know what to recommend if their friends or relatives had epilepsy. Youth, higher education, and upper levels of employment were correlated with answers that were more favorable concerning epilepsy in all survey questions except for the question regarding marriage, for which the reverse was noted. The attitudes toward epilepsy disclosed by this study were more favorable than those detected in a similar survey conducted in Henan Province, China. The comparison suggests that the exposure to Western culture and socioeconomic system in Taiwan might have helped reduce the discrimination against epilepsy.

Conventional laser stimulation at the acupoint can induce significant brain activation, and the activation is theoretically conveyed by the sensory afferents. Whether the insensible low-level Laser stimulation outside the acupoint could also evoke electroencephalographic (EEG) changes is not known. We designed a low-level laser array stimulator (6 pcs laser diode, wavelength 830 nm, output power 7 mW, and operation frequency 10 Hz) to deliver insensible laser stimulations to the palm. EEG activities before, during, and after the laser stimulation were collected. The amplitude powers of each EEG frequency band were analyzed. We found that the low-level laser stimulation was able to increase the power of alpha rhythms and theta waves, mainly in the posterior head regions. These effects lasted at least 15 minutes after cessation of the laser stimulation. The amplitude power of beta activities in the anterior head regions decreased after laser stimulation. We thought these EEG changes comparable to those in meditation.

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. 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. 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 (> or = 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. 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.

Case reports with a comprehensive review of the current literature concerning subacute combined degeneration induced by nitrous oxide inhalation. A differential diagnosis should be considered when young patients present with progressive myelopathy because that the misuse of nitrous oxide has potentially serious outcomes.Three young patients aged from 18 to 24, one male and two females, were diagnosed with progressive ascending numbness in four limbs or both legs and ataxia. They all had been inhaling nitrous oxide from whipped-cream containers for several months. A cervicothoracic magnetic resonance imaging scan revealed long segmental hyperintensity changes at the posterior column of the spinal cord. Serological examination showed a low level of vitamin B12. Subacute combined degeneration of the spinal cord was diagnosed and the etiology was considered related to nitrous oxide misuse. Their neurological status, neuroimage, and neurophysiologic condition improved after vitamin B12 supplementation and cessation of nitrous oxide inhalation.Iatrogenic usage of nitrous oxide apparently resulted in subacute combined degeneration in our three patients. Recently, nitrous oxide misuse has increased among young people. Subacute combined degeneration of the spinal cord should be considered as a possible outcome of such abuse.

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, norm5.88 fibres/mm) and significant elevation of the warm threshold in the foot (40.0 degrees C, norm39.4 degrees 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 degrees 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.

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.

Electroneurographic (ENeG) and evoked potential (EP) studies were regularly performed on 11 printing workers with n-hexane polyneuropathy after cessation of exposure. At the initial examination, the ENeG studies simulated a demyelinative process. Further slowing of nerve conduction velocity, or further decreasing of action potential amplitude, or both in the follow up ENeG study were found in about half the patients. The motor distal latency did not worsen. Nerve conduction returned to normal earlier in the sensory than in the motor nerves. After the patients had regained full motor capability, conduction velocities in motor nerves were still significantly slowed. These ENeG characteristics correlate with the pathological and pathophysiological changes in experimental hexa-carbon neuropathies. The initial findings from the EP studies indicated a conduction abnormality in the central nervous system (CNS). Delayed worsening occurred in the amplitude of visual EPs in three patients. On serial follow up, the interpeak latency and interpeak amplitude of visual EPs improved little. Residual abnormalities were also found in the interpeak latency of auditory EPs in the brainstem and in the absolute latency of scalp somatosensory EPs from the peroneal nerve. Astroglial proliferation in the CNS probably impedes recovery of the abnormalities in EP.

Objective Contact heat evoked potentials (CHEPs) provide an objective approach to investigate cerebral responses to thermal stimuli mediated by Aδ 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 °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 ± 1.70 fibers/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 ± 4.06 m/s (range: 6.06–16.60), in the range of Aδ fibers. The group of neuropathic patients had markedly reduced N–P amplitudes ( p 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 Aδ 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.

During the worldwide outbreak of severe acute respiratory syndrome (SARS) in 2002-2003, there were 664 probable SARS patients reported in Taiwan. SARS patients usually present with symptoms related to the respiratory system while neurological manifestations have rarely been described. There were three patients who developed axonopathic polyneuropathy 3-4 weeks after onset of SARS; their clinical condition and electrophysiological studies revealed obvious improvement at follow-up. Two SARS patients have experienced myopathy and three other patients developed rhabdomyolysis. These neuromuscular disorders in SARS patients were considered as critical illness neuropathy and myopathy, but the possibility of direct attack by SARS coronavirus on the nerve and muscle could not be excluded. Large artery ischemic stroke were described in five SARS patients with poor prognosis. Multiple factors contributed to this vascular insult included hypercoagulabe status related to both SARS coronavirous and the usage of intravenous immunoglobulin, septic and cardiogenic shock, and possible vasculitis. The relationship between SARS and above neurological problems still needs further clarification. Pathological and microbiological studies are mandatory to delineate this issue.

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.

To investigate mortality in adult patients with epilepsy in Taiwan, a total of 263 patients with epilepsy agedor = 17 years, referred to the outpatient epilepsy clinic between 1 Jan and 31 December 1991, were prospectively enrolled and followed up until 31 December 2000. A total of 32 deaths were reported. Overall case-fatality rate was 12.2%. The age-adjusted standard mortality ratio (SMR) was calculated to compare the risk of death in patients with epilepsy to the general population. Patients with epilepsy had a 3.5-fold higher risk of death as compared with the general population (SMR: 3.47, 95% CI: 2.46-4.91). The Cox proportional hazards regression model was used to assess relevant clinical contributions to death. Patients with an age-at-onsetor = 40 years had a 4-fold higher risk of death as compared with those with an earlier onset. The multivariate analysis revealed that age-at-onset between 40 and 59 years, tumor etiology, and being male increased the risk of death in epilepsy. One-third of the deaths in patients with age-at-onset between 40-59 years died of liver cirrhosis and hepatoma. Hepatitis B virus infection is endemic in Taiwan, and this is closely associated with liver cirrhosis and hepatoma. Whether anticonvulsants contributed to the hepatotoxicity that led to fatal liver disease in this group needs further investigation.

Sensory neuropathy is a prominent component of diabetic neuropathy. It is not entirely clear how diabetes influences skin innervation, and whether these changes are correlated with clinical signs and laboratory findings. To investigate these issues, we performed skin biopsies on the distal leg of 38 consecutive type 2 diabetic patients with sensory symptoms in lower limbs (25 males and 13 females, aged 56.2 +/- 9.4 years) and analysed the correlations of intraepidermal nerve fibre (IENF) densities in skin with glycaemic status (duration of diabetes, HbA1C, and fasting and post-prandial glucose levels), and functional parameters of small fibres (warm and cold thresholds) and large fibres (vibratory threshold and parameters of nerve conduction studies). Clinically, 23 patients (60.5%) had signs of small-fibre impairment, and 19 patients (50.0%) had signs of large-fibre impairment. IENF densities were much lower in diabetic patients than in age- and gender-matched controls (1.794 +/- 2.120 versus 9.359 +/- 3.466 fibres/mm, P < 0.0001), and 81.6% (31/38) of diabetic patients had reduced IENF densities. IENF densities were negatively associated with the duration of diabetes (standardized coefficient: -0.422, P = 0.015) by analysis with a multivariate linear regression model. Abnormal results of functional examinations were present in 81.6% (warm threshold), 57.9% (cold threshold), 63.2% (vibratory threshold) and 49% (amplitude of sural sensory action potential) of diabetic patients. Among the three sensory thresholds, the warm threshold temperature had the highest correlation with IENF densities (standardized coefficient: -0.773, P < 0.0001). On nerve conduction studies in lower-limb nerves, there were abnormal responses in 54.1% of sural nerves, and 50.0% of peroneal nerves. Of neurophysiological parameters, the amplitude of the sural sensory action potential had the highest correlation with IENF density (standardized coefficient: 0.739, P < 0.0001). On clinical examination, 15 patients showed no sign of small-fibre impairment, but seven of these patients had reduced IENF densities. In conclusion, small-fibre sensory neuropathy presenting with reduced IENF densities and correlated elevation of warm thresholds is a major manifestation of type 2 diabetes. In addition, the extent of skin denervation increases with diabetic duration.

To understand the eiect of aging on human skin innervation, we investigated intraepidermal nerve ¢ber (IENF) density of skin biopsies. IENF densities of the distal leg were lower in elderly (Z 60 years of age) than in young adults (19^39 years of age; 7.807 0.79 vs 13.557 0.85 ¢bers/mm, po 0.01). A similar trend was also observed in the distal forearm (11.677 1.55 vs 19.39 7 1.60 ¢bers/ mm, po 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 coe⁄cients of � 0.462 (po 0.001) in the distal leg and � 0.335 (p ¼ 0.005) in the distal forearm.These ¢ndings suggest a signi¢cant reduction in IENF densities with age. NeuroReport15:149^153 � c 2004 Lippincott Williams & Wilkins.

Severe acute respiratory syndrome (SARS), an infection caused by a novel coronavirus,1 is a life-threatening respiratory disease, which has broken out worldwide. Although the clinical features in the epidemic areas have been reported in detail,2 no neurologic manifestations have been mentioned. We report a SARS patient who developed acute paresthesia and weakness in her lower limbs during the period of mechanical ventilator support. The husband of a previously well 51-year-old woman returned to Taiwan in February 2003 from a 16-day stay in Guangdong, China, and began to experience fever (>38 °C), cough, and myalgia on February 25. Progressive respiratory distress was noted, and chest x-ray (CXR) showed bilateral pneumonia. He was intubated on March 10. Based on the traveling history, clinical manifestations, and CXR findings, he was diagnosed with probable SARS.3 His wife then developed high fever (39.1 °C), sore throat, watery diarrhea, and cough with dyspnea. Her CXR taken on March 14 showed increased infiltration in the right lower lobe. Laboratory studies showed raised glutamic-pyruvic transaminase and lactate dehydrogenase …

Neurotrophins are target-derived trophic factors essential for the survival and maintenance of neurons. Among these, nerve growth factor (NGF) and neurotrophin-3 (NT-3) are particularly important for sensory neurons. The actions of neurotrophins are through the p75 low-affinity receptor and the high-affinity receptor tyrosine kinase (trk). Each neurotrophin has its preferred receptor, i.e. trkA for NGF, and trkC for NT-3. The primary sensory neurons in the dorsal root ganglion are classified into two categories, namely, the large and small sensory neurons based on their size. The large sensory neurons with the expression of trkC depend on NT-3 for development and subserve the function of position sensations. Some of the small sensory neurons express trkA and are NGF-dependent. They are responsible for nociceptive sensation, the detection of painful and thermal stimuli. A more intriguing observation is the bidirectional interactions between nociceptive nerves and their target, the skin. The peripheral processes of small sensory neurons innervate the epidermis of the skin as 'free nerve endings'. In denervated skin, there is a drastic reduction in the epidermal thickness, a finding corroborated by the phenomenon of trophic change, the shining and thinning of the skin, in the disorders of peripheral nerves. The performance of animals with peripheral nerve disorders improved after administration of neurotrophic factors. Based on these results, the therapeutic potentials of neurotrophic factors in human are under investigation.

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.

Sensory innervation of the skin subserves protective sensations for the body to prevent thermal and noxious injuries. Neurophysiologically, they belong to the categories of Adelta and C fibers, usually with caliber less than one micro m in diameter. Morphological demonstration of the terminals of these nerves in the epidermis has been recognized recently by sensitive immunocytochemistry and an axonal marker, the protein gene product 9.5 (PGP). PGP is a ubiquitin C-terminal hydrolase, which is abundantly present in the nervous system, and particularly enriched in the unmyelinated nerves. Sensory nerves positive for PGP arise from the dorsal root ganglion, pass through the dermis, parallel the epidermis-dermis border, penetrate the basement membrane, move vertically and upwards in the epidermis with tortuous course and knobby appearance, and finally terminate at the granular layers of the epidermis. In rodents, denervation of the skin results in degeneration of epidermal nerves within 48 h of nerve transection, and thinning of the epidermis. In humans, application of this technique to evaluate disorders of the peripheral nervous system makes study of the degeneration of sensory nerve terminals possible. Patients with sensory neuropathy had fewer epidermal nerves than normal subjects, consistent with the notion of distal axonopathy. This approach has the potential to evaluate human sensory neuropathy in temporal and spatial domains. In addition, the influences of epidermal denervation open a new field to explore the interactions between sensory nerves and keratinocytes.

This report was designed to assess response of the renal nerve activity (RNA) during and after renal ischemia in chronic hypoxic rats. Hypoxia was induced by placing the female Wistar rats in an altitude chamber set at 5500 m for 4 weeks. Simultaneous recordings of left renal efferent (RENA) and afferent (RANA) nerve activity were performed in each pentobarbital-anesthetized rat throughout the experiment. Ischemic renal failure was induced by complete occlusion of the left renal artery for 45 min. During renal arterial occlusion (RAO), RENA gradually decreased while RANA enhanced initially and then this decreased gradually in both sea level (SL) controls and chronic hypoxic (high-altitude; HA) rats. During 45 min of reperfusion, RENA depressed more in comparison with RANA in both groups of animals. In addition, RANA returned to baseline level in SL rats, while it remained elevated in HA rats. In the second experiment, six groups of renal ischemic rats were challenged by rapid intravenous infusion of 10 ml of saline, and urine was collected for 90 min from the left ureter. Baseline RENA was low in rats 4 h after RAO of SL (4SL) and of HA (4HA) groups. The effects of saline loading on RENA and RANA were different in HA and SL rats. Saline loading significantly decreased RENA but increased RANA more in SL rats. Following saline loading, RENA in 4SL and 4HA rats, as well as animals 24 h after RAO of SL (24SL) and HA (24HA) were comparable to their respective SL or HA animals. In 4SL rats, RANA was significantly enhanced, and remained elevated during saline loading and the recovery period. In 4HA, 24HA and 24SL rats, RANA reduced significantly during saline loading, then its activity returned to the baseline value. The insulted kidneys showed increased renal excretion of water and sodium in 4SL and 4HA rats. Urinary excretion reduced significantly in 24SL rats but was almost normal in 24HA rats. These results indicate that a decrease in RENA may play a protective role in response to renal ischemia in both SL and HA rats. In response to renal ischemia and saline loading, different alterations of RANA in SL and HA rats may reflect a beneficial mechanism located in the hypoxia-pretreated kidney.

Effects of paraquat on the substantia nigra of the male Wistar rats we re studied pharmacologically by a intracerebral injection of paraquat. The neurochemical, morphological, and behavioral changes observed after a unilateral intranigral injection of paraquat (1-5 microgram) were as follows: (1) neurochemically, paraquat caused dose-dependent depletion of dopamine in the ipsilateral striatum starting 2 weeks after treatment; this effect was long-lasting and irreversible. The ipsilateral striatal dopamine level in animals treated with 3 microgram paraquat was even decreased by 91.5%. (2) Morphologically, 2 microgram of paraquat produced marked loss of Nissl substances and prominent glial reaction in the substantia nigra, while 3 microgram of paraquat caused a severe loss of neurons. (3) Behaviorally, paraquat caused a vigorous rotational behavior in rats contralateral to the lesioned side in response to apomorphine administration (0.5 mg/kg, sc). This effect was dose-dependent and lasted for the entire 16-week experimental period. Taken together, these data indicate that intranigrally injected paraquat may possess marked neurotoxicity and induce degeneration of the rat nigrostriatal dopaminergic system.

OBJECTIVES--To evaluate the effects of chronic exposure to lead on the peripheral nervous system in lead workers. METHODS--Nerve conduction velocity and electromyographic studies were performed on 31 lead workers of a battery recycling factory and 31 sex and age matched controls. 25 cases with mild distal extensor weakness of the upper limbs were classified as the lead neuropathy subgroup and the rest of the lead workers as the lead exposure subgroup. Blood lead concentrations and haematological and biochemical data were recorded. An index of cumulative exposure to lead was calculated by the summation of multiplying the average blood concentration of lead with the duration of exposure at various jobs. RESULTS--Compared with the control group, the distal motor latency of the median nerve was significantly prolonged in the lead neuropathy subgroup, but not in the exposure subgroup. Only six of 31 workers had nerve conduction abnormalities, whereas electromyographic evidence of denervation was found in 93.5% of the lead neuropathy subgroup and 83.5% in the lead exposure subgroup. The electromyographic abnormalities found were neurogenic polyphasic waves in all 29 workers with abnormal electromyographic findings (grade in seven cases and grade ++ in the rest). Spontaneous activity was only recorded in seven workers, with grade + in four and grade ++ in three. There was a positive linear correlation between the index of cumulative exposure to lead and the distal motor latencies of the tibial nerve as well as a negative correlation with conduction velocities of the sural nerve after multivariate analysis and control of potential confounding by age and sex. No correlation could be found between the electrophysiological values and a simple duration of exposure or concentration of blood lead. A non-parametric analysis showed that there was a trend of higher index of cumulative exposure to lead with more severe electromyographic changes. Electromyographic abnormality also occurred in workers with blood lead concentrations between 17.4 and 58 micrograms/dl. CONCLUSION--Electromyographic study in the distal extensors of the upper limbs may be used as a tool for biological monitoring of effect in lead workers.

Four patients with the classic form and 1 patient with the connatal form of Pelizaeus-Merzbacher disease were studied with magnetic resonance imaging, electroencephalography, and multimodal evoked potentials, including brainstem auditory evoked potentials, somatosensory evoked potentials, and visual evoked potentials. Comparisons between these findings were made. It was determined that the neurophysiologic studies, particularly brainstem auditory evoked potentials, are of value in early diagnosis of Pelizaeus-Merzbacher disease; brainstem auditory evoked potentials with only normal wave I may be a relatively reliable clue suggesting the classic form of Pelizaeus-Merzbacher disease in patients with nystagmus and chronic progressive encephalopathy. Magnetic resonance imaging allows an accurate assessment of the degree of hypomyelination; however, the clinical severity of various forms of Pelizaeus-Merzbacher disease seemed to be independent of the age of onset and the amount of residual myelin. The following may be distinguishing features between the connatal and classic forms of Pelizaeus-Merzbacher disease: hypoplasia of the cerebellum and brainstem, and diffuse brain atrophy on magnetic resonance imaging; optic atrophy with abnormal visual evoked potential; seizure disorder with abnormal electroencephalography, and/or auditory nerve impairment with abnormal wave I of brainstem auditory evoked potentials in the early stage of the disease.

Wilson's disease (WD) is a rare autosomal recessive disorder and has been mapped to the long arm of chromosome 13 (q14.1). We have analyzed the segregation of esterase D (ESD) and retinoblastoma (RB) gene loci in ten families of Chinese WD subjects living in Taiwan. The polymorphic information content (PIC) for ESD and RB was 0.18 and 0.31, respectively. We confirmed a tight linkage between these loci and WD with a lod score of 3.33 by multipoint linkage analysis. The data from this limited number of pedigrees also suggested the following order: centromere-WD-RB-ESD or centromere-ESD-RB-WD. ESD in conjunction with RB polymorphism would be useful in prenatal and presymptomatic diagnosis, as well as in carrier detection in informative pedigrees.

A prospective study was made to evaluate the effect of intrathecal injection of iohexol on brainstem auditory evoked potentials (BAEP) following myeloradiculography, in order to assess its neurotoxicity. Thirty patients who received contrast medium via the lumbar route for myeloradiculography (cervical level = 25 patients, lumbar level = 5 patients) had BAEP examinations before, 2 h and 24 h after myelography. No statistically significant prolongation of absolute and interpeak latencies was found between premyelographic and postmyelographic records. Low incidence (20%) of insignificant clinical adverse effect following myelography was also noted in the same group of patient.

A 23 year old male developed abdominal pain, diarrhoea, and vomiting several hours after poisoning with acute triphenyltin intoxication in a suicide attempt. Severe ataxia, dysmetria, nystagmus, and blurring of vision soon supervened. Disturbance of consciousness and confusion developed 12 days later and lasted for two months. A delayed sensorimotor polyneuropathy was shown by electrophysiological studies to be due to axonal degeneration and demyelination. The neuropathy rapidly recovered after consciousness was regained.

A woman developed a severe generalized polyneuropathy in acute lithium intoxication. Nerve conduction studies suggested an axonal neuropathy. Her peripheral nerve problem became manifest after treatment had already started; therefore, a high serum lithium level is not considered to be the only factor for the development of a severe polyneuropathy in lithium intoxication.