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Background/Purpose: Multiple sclerosis is classified as a rare disease in Taiwan. This study evaluated the safety and effectiveness of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) from routine clinical practice in Taiwan. Methods: In this retrospective, multicentre, observational study, we collected clinical data of patients treated with fingolimod 0.5 mg/day in routine clinical practice between September 2012 and December 2015. Primary outcome was the overall safety of fingolimod; secondary outcome was the annualized relapse rate (ARR). Results: Overall, 62/69 (86.1%) patients were on fingolimod by the end of data collection period. Mean age (±standard deviation [SD]) at inclusion was 37.7 ± 10.10 years; mean duration of MS was 5.4 ± 4.52 years and mean duration of fingolimod exposure was 135.8 patient-years. The most common adverse events (AEs) were bradycardia (21.7%; first-dose related), upper respiratory tract infection, dizziness, and hypoaesthesia (numbness) (11.6% each), followed by urinary tract infection and back pain (7.2% each). Seven patients had liver enzyme-related AEs. Eight patients had absolute lymphocyte counts

International audience; Background: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.Methods: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume.Results: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P

The autosomal recessive Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum (HMSN/ACC) is associated with the dysfunction of the K + –Cl − cotransporter type 3 (KCC3), which is an electroneutral cotransporter. We previously found that the inhibition of KCC3 cotransporter activity reduces the propagation of action potentials in the peripheral nervous system (PNS). However, the pathogenesis by which KCC3 deficiency impairs peripheral nerve function remains to be examined. Thus, we conducted imaging and electrophysiological studies in the peripheral nerves of KCC3 −/− mice at various ages. Analysis using transmission electron microscopy (TEM) revealed an age-dependent progressive swelling of microvilli and disorganization of paranodal loops in KCC3 −/− nerves. Yet, no mislocated voltage-dependent channels were observed between the nodes and juxtaparanodes of KCC3 −/− nerves. However, electrophysiological studies using the threshold tracking technique indicated a reduced stimulus–response curve slope with an elevated rheobase, a decreased strength–duration time constant, diminished persistent Na + currents, and an outward deviation of threshold electrotonus in KCC3 −/− nerves compared to wild-type nerves. These functional changes indicate an overall reduction in axonal excitability and suggest an increase in paranodal conductance, which was relevant to the pathology at the paranode. Altogether, our findings highlight the importance of KCC3 in maintaining paranodal integrity and in optimizing the propagation of action potentials along peripheral nerves.

Point mutations in the peripheral myelin protein 22 (PMP22) gene have been identified to cause demyelinating Charcot-Marie-Tooth disease (CMT) and hereditary neuropathy with liability to pressure palsy (HNPP). To investigate the mutation spectrum of PMP22 in Han-Chinese population residing in Taiwan, 53 patients with molecularly unassigned demyelinating CMT and 52 patients with HNPP-like neuropathy of unknown genetic causes were screened for PMP22 mutations by Sanger sequencing. Three point mutations were identified in four patients with demyelinating CMT, including c.256 C > T (p.Q86X) in two, and c.310delA (p.I104FfsX7) and c.319 + 1G > A in one each. One PMP22 missense mutation, c.124 T > C (p.C42R), was identified in a patient with HNPP-like neuropathy. The clinical presentations of these mutations vary from mild HNPP-like syndrome to severe infantile-onset demyelinating CMT. In vitro analyses revealed that both PMP22 p.Q86X and p.I104FfsX7 mutations result in truncated PMP22 proteins that are almost totally retained within cytosol, whereas the p.C42R mutation partially impairs cell membrane localization of PMP22 protein. In conclusion, PMP22 point mutations account for 7.5% and 1.9% of demyelinating CMT and HNPP patients with unknown genetic causes, respectively. This study delineates the clinical and molecular features of PMP22 point mutations in Taiwan, and emphasizes their roles in demyelinating CMT or HNPP-like neuropathy.

Introduction Uric acid (UA) may act as an antioxidant in ALS pathophysiology. This study examined whether serum UA concentration correlates to clinical course in the ALS patients. Methods We measured serum UA levels in 51 sporadic ALS patients, and compared them to 51 age-and-gender-matched healthy subjects. We analyzed the correlation between serum UA levels, illness duration, and disease “course factors” (defined as “disease duration” over “terminal time”) in the ALS patients. Results The mean serum UA levels in the ALS groups were higher than the control groups in both genders. Serum UA levels were inversely correlated with the disease “course factors” in the ALS male patients. Discussion The elevation of serum UA concentration in ALS patients may be related to oxidative stress. The reasons that serum UA levels inversely correlated with ALS “course factors” include: muscle wasting, poor nutrition, reduced antioxidant reserve, or increased UA consumption in end-stage patients.

Nerve conduction requires the fine tuning of ionic currents through delicate interactions between axons and Schwann cells. The K(+)-Cl(-) cotransporter (KCC) family includes four isoforms (KCC1-4) that play an important role in the maintenance of cellular osmotic homeostasis via the coupled electroneutral movement of K(+) and Cl(-) with concurrent water flux. Mutation in SLC12A6 gene encoding KCC3 results in an autosomal recessive disease, known as agenesis of the corpus callosum associated with peripheral neuropathy. Nevertheless, the role of KCC3 in nerve function remains a puzzle. In this study, the microscopic examination of KCC isoforms expressed in peripheral nerves showed high expression of KCC2-4 in nodal segments of the axons and in the perinucleus and microvilli of Schwann cells. The KCC inhibitor [[(dihydroindenyl)oxy]alkanoic acid] but not the Na(+)-K(+)-2Cl(-)-cotransport inhibitor (bumetanide) dose-dependently suppressed the amplitude and area of compound muscle action potential, indicating the involvement of KCC activity in peripheral nerve conduction. Furthermore, the amplitude and area under the curve were smaller, and the nerve conduction velocity was slower in nerves from KCC3(-/-) mice than in nerves from wild-type mice, while the expression pattern of KCC2 and KCC4 was similar in KCC3 kockout and wild-type strains. KCC3(-/-) mice also manifested a prominent motor deficit in the beam-walking test. This is the first study to demonstrate that the K(+)-Cl(-) cotransporter activity of KCC3 contributes to the propagation of action potentials along peripheral nerves.

Objectives This study sought to examine the hypothesis that cardiac autonomic function (CAF) is altered in pre-hypertensive subjects and normotensive subjects with a family history of hypertension (FHH). Background The findings on the FHH effect in CAF have been inconsistent, and little is known about altered CAF in pre-hypertensive subjects under The Seventh Report of the Joint National Commission on High Blood Pressure criteria of normotension and pre-hypertension. Methods A total of 1,436 community dwellers were classified as having normotension without FHH (NT[−]), normotension with FHH (NT[+]), pre-hypertension, and hypertension. Cardiac autonomic function was determined by standard deviation of RR intervals (SDNN), power spectrum in low frequencies (LF) and high frequencies (HF) and LF/HF ratio in supine position for 5 min, the ratio between the longest RR interval at approximately the 30th beat and the shortest RR interval at approximately the 15th beat after standing (30 max/15 min ratio), and the ratio between the longest RR interval during expiration and the shortest RR interval during inspiration (E/I ratio). Results There was a significant difference in all CAF indexes among subjects with NT(−), NT(+), pre-hypertension, and hypertension. Multivariate analyses with an analysis of covariance model showed that 30 max/15 min ratio, E/I ratio, and HF power decreased in subjects with NT(+), pre-hypertension, and hypertension when compared with NT(−) subjects. Pre-hypertensive and hypertensive subjects displayed higher square roots of LF/HF ratios. Only pre-hypertensive subjects had higher LF power. Conclusions Our study provides evidence that CAF plays a role in pre-hypertension and that altered autonomic function is already present in subjects with FHH. An autonomic imbalance shifting with augmented sympathetic tone was more enhanced in pre-hypertension.

Context: Autonomic dysfunction is present in diabetes mellitus (DM), but no study is available on alteration in cardiac autonomic function (CAF) across different glycemic statuses including normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and DM. Objective: Our objective was to examine whether CAF is altered in subjects with IGT and isolated IFG. Design and Setting: The study was a stratified systematic cluster sampling design within the general community. Participants: A total of 1440 subjects were classified as NGT (n 983), isolated IFG (n 163), IGT (n 188), and DM (n 106). Main Outcome Measure: CAF was determined by 1) standard deviation of normal-to-normal (SDNN) or RR interval, power spectrum in low and high frequency (LF, 0.04–0.15 Hz; HF, 0.15–0.40 Hz), and LF/HF ratio in supine position for 5 min; 2) ratio between 30th and 15thRRintervalafterstandingfromsupineposition(30/15ratio);and 3) average heart rate change during breathing of six deep breaths for 1 min (HRDB). Results: Univariate analysis showed significant differences in SDNN,30/15ratio,HRDB,HFpower,andLF/HFratioamongsubjects with NGT, isolated IFG, IGT, and DM. In multivariate analysis, none oftheindicesofCAFwasrelatedtoisolatedIFGinthereferencegroup of NGT. IGT and DM were negatively associated with 30/15 ratio and HF power but positively associated with LF/HF ratio. In addition, DM was also related to a lower SDNN. Conclusions: DM and IGT subjects had an impaired CAF independent of other cardiovascular risk factors. The risk of altered CAF is not apparent in subjects with isolated IFG. (J Clin Endocrinol Metab 92: 3885–3889, 2007)

Objective: To establish and evaluate the effectiveness of a comprehensive next-generation sequencing (NGS) approach to simultaneously analyze all genes known to be responsible for the most clinically and genetically heterogeneous neuromuscular diseases (NMDs) involving spinal motoneurons, neuromuscular junctions, nerves, and muscles. Methods: All coding exons and at least 20 bp of flanking intronic sequences of 236 genes causing NMDs were enriched by using SeqCap EZ solution-based capture and enrichment method followed by massively parallel sequencing on Illumina HiSeq2000. Results: The target gene capture/deep sequencing provides an average coverage of ∼1,000× per nucleotide. Thirty-five unrelated NMD families (38 patients) with clinical and/or muscle pathologic diagnoses but without identified causative genetic defects were analyzed. Deleterious mutations were found in 29 families (83%). Definitive causative mutations were identified in 21 families (60%) and likely diagnoses were established in 8 families (23%). Six families were left without diagnosis due to uncertainty in phenotype/genotype correlation and/or unidentified causative genes. Using this comprehensive panel, we not only identified mutations in expected genes but also expanded phenotype/genotype among different subcategories of NMDs. Conclusions: Target gene capture/deep sequencing approach can greatly improve the genetic diagnosis of NMDs. This study demonstrated the power of NGS in confirming and expanding clinical phenotypes/genotypes of the extremely heterogeneous NMDs. Confirmed molecular diagnoses of NMDs can assist in genetic counseling and carrier detection as well as guide therapeutic options for treatable disorders.

Munksgaard 2001.Objectives – Fatigue is a disabling and dopa-resistant symptom inParkinson’s disease (PD). Pathological studies have shown that bothperipheral and central cholinergic systems are involved in PD.Electrophysiological investigation showed decremental muscleresponses following repetitive nerve stimulation (RNS). We hypothe-sized that fatigue in PD patients may be secondary to cholinergic defectat the neuromuscular level. Material and methods – Twenty PD patientswith disabling fatigue symptoms were enrolled. We used stimulatedsingle fiber electromyography (s-SFEMG) to evaluate the neuromus-cular junction of these patients. For every patient, at least 15 musclefibers were tested at the rate of 10 Hz with the method described byTrontelj et al. The individual mean consecutive difference (i-MCD) wasobtained from 100 constant consecutive single fiber potentials. Thei-MCD values in each patient were averaged to obtain the mean MCD(m-MCD). Results – None of the 20 PD patients with disabling fatiguesymptoms had an m-MCD over 29 ms or more than 10% of the i-MCDvalues over 41 ms. The neuromuscular junction was intact in terms ofnormal jitter (expressed as MCD) and an absence of blocking.Conclusion – Our findings indicate that the cholinergic system at theneuromuscular level is not affected in PD patients with fatiguesymptoms.W. J. Hwang, T. S. Lin

We report a patient suffering from delayed encephalopathy 21 days after an acute CO intoxication. The initial magnetic resonance (MR) images in the acute stage show a recent infarct corresponding to a right middle cerebral artery (MCA) stenosis. MR images on the 24th day post-intoxication show typical changes of delayed encephalopathy. These changes were much more prominent on the areas corresponding to right MCA territory while less severe on the other parts. The finding suggests an ischemic component contributes to carbon monoxide related delayed brain injury.

Spasticity after a stroke is usually assessed in a score form by subjectively determining the resistance of a joint to an externally imposed passive movement. This work presents a spasticity measurement system for on-line quantifying the stretch reflex of paretic limbs. Four different constant stretch velocities in a ramp-and-hold mode are used to elicit the stretch reflex of the elbow joint in spastic subjects. The subjects are tested at supine position with the upper limb stretched towards the ground, in contrast with the horizontally stretched movement used in other studies. By subtracting the baseline torque, reflex torque measured at a selected low stretch velocity of 5 deg/sec, the influence of gravity torque and inertial in vertical stretching mode can be minimized. The averaged speed-dependent reflex torque (ASRT), defined as the measured torque deviated from the baseline torque, is used for quantifying the spastic hypertonia. Four subjects having incurred cerebrovascular accident (CVA) are recruited for time-course study in which the measurements are taken at 72 hours, one week, one month, three months, and six months after onset of stroke. During the development of spasticity, the changes of ASRT and velocity sensitivity of ASRT of the involved and the intact elbow joints are discussed.

Objective: One of the important characteristics of myofascial trigger point [MTrP] is spontaneous electrical activity [SEA]. Spontaneous electrical activity is recorded from an active locus [a basic unit] of MTrP and has been considered as an abnormal endplate potential, which might be due to excessive acetylcholine release in neuromuscular junction. This study is designed to test the hypothesis that active loci in MTrPs are related to neuromuscular transmission disorder.Methods: Twenty-one adult New Zealand rabbits were anesthetized and their biceps femoris were exposed to localize myofascial trigger spot [MTrS, equivalent to MTrP in human]. A monopolar needle electrode was first used for searching SEA in an MTrS region. Then, a single fiber electromyography [SFEMG] electrode was used to collect the neuromuscular jitter at the site where SEA was recorded. The same procedure was performed at the normal muscle site [no SEA recorded] in contralateral limb to collect the neuromuscular jitter as a control. Me...

We applied the singular value decomposition (SVD) method to study single motor unit firing patterns. Two projects were carried out: (1) a computer simulation study to confirm the meanings of two SVD parameters, the eigenvalue corresponding to the positive-slope eigenvector (PEV) and that corresponding to the negative-slope eigenvector (NEV); and (2) a clinical study for which electromyographic (EMG) recordings were made from first dorsal interosseous muscle in patients with stroke, myopathies, or neuropathies and in healthy control subjects. Results of computer simulation reveal that the NEV reflects the amount of instantaneous firing variability, whereas the PEV/NEV (P/N) ratio exhibits the relative effect of a trend in the firing pattern. In human studies, the P/N ratio of stroke patients was significantly higher than that of the controls, whereas their NEV was comparable. By contrast, in the myopathy and neuropathy groups, the NEV increased significantly, whereas the P/N ratio did not. These results suggest that the SVD method decomposes the motor unit (MU) firing variation into two components and that the mechanism for increased firing variability is different for supraspinal and spinal-infraspinal lesions.

To noninvasively estimate the motor unit size, we present a novel surface electromyographic (EMG) measurement system consisting of a surface multielectrode with four-pin electrodes and a pair of surface-disk electrodes. Surface motor unit action potentials (MUAPs) were recorded with the multielectrode, in the so-called multielectrode surface EMG (MSEMG), which was spatially filtered to localize the sensing area and reduce the noise. In addition, a modified decomposition algorithm, considering the geometrical configuration of the multielectrode, was designed to identify the individual MUAPs in the measured MSEMG. The identified MUAP was subsequently used as the triggering source for the EMG signals recorded by the surface-disk electrodes. From a pool of 34 subjects with neuromuscular diseases and 14 normal subjects, the median amplitudes of surface-disk EMG after spike-triggered averaging, called MSEMG-MUAP, correlated well (r = 0.82, P < 0.0001) with those of macro EMG. Moreover, the MSEMG-MUAP recording during a ramp force contraction exhibited the common size principle phenomenon during motor unit recruitment. The results of this study demonstrate that the MSEMG-MUAP measurement is a feasible approach for estimating the motor unit size from the skin surface.

Twenty patients with generalized myasthenia gravis (MG) were studied to assess firing rate-dependent changes in end-plate jitter. Stimulated single-fiber electromyography (EMG) was performed in the extensor digitorum communis muscles at stimulation frequencies of 1, 2, 5, and 10 Hz for all the sampled fibers and at 20 Hz for a few ones. In all 137 end-plates were obtained, of which 43 showed blocking. Statistical analysis demonstrated significant increases in jitter and the blocking rate from 1 to 2 and 2 to 5 Hz, whereas there were decreases from 5 to 10 and 10 to 20 Hz. Further analysis showed that the decrement in jitter from 5 to 10 Hz was greater in end-plates with preexisting low safety factors. In contrast, even though the safety factor of long-duration MG end-plates was lower than that of the short-duration group, the decrement in jitter was insignificant in the long-duration MG end-plates. These results suggest that the intratetanic facilitation effect begins at 10 Hz and is more prominent in end-plates with a preexisting low safety factor. Long-lasting MG, however, eliminates this effect.

A mathematical model developed for a personal computer was used to simulate the jitter phenomenon in neuromuscular transmission in order to characterize the relationship between jitter and the safety factor. Four models of normal and abnormal neuromuscular transmission were investigated. In a human experiment, the mean consecutive difference (MCD) values for stimulated single-fiber electromyography at firing rates of 1, 2, 5, and 10 Hz were measured in 137 motor end-plates of myasthenic patients. Results of the computer simulations show that the relationship between jitter and the safety factor is exponential like. Variations in jitter are most prominent in end-plates with low safety factors. This relationship agrees with results of human end-plate studies. Changes in the MCD values caused by presynaptic depression or facilitation are linearly correlated to the initial jitter, whereas the logarithmic values of MCD are not. It is very important to keep in mind this nonlinear relationship when relating single-fiber jitter to the safety factor.

We constructed an animal model of stimulated single-fiber electromyography (SFEMG) by testing Wistar rats under anesthesia. Stimuli of 1 Hz were applied to the sciatic nerve through an insulated monopolar needle electrode. Single-fiber action potentials were acquired from the gastrocnemius muscle. Jitter was assessed by the mean consecutive difference (MCD). Eighty-seven fibers were obtained from 12 rats. Their MCDs ranged from 2 to 72 μs (17.7 ± 13.4). Seven of these values were less than or equal to 5 μs, and three exceeded 50 μs. Neuromuscular blocking agents injected into some of the rats induced considerable increases in jitter and blocking. A rat with one fiber with an MCD less than 5 μs also received an injection of curare. The jitter showed the same pattern of increment, evidence that the small jitter was not attributable to direct muscle stimulation. These results show that SFEMG can be used on rats. In addition, jitter reflects the changes in motor end-plate function. The findings also suggest the presence of an extremely high safety factor in rat neuromuscular junctions. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:482–489, 1998.

Background and aims To explore the impact of cardiac autonomic function (CAF) and insulin resistance (IR) on incident hypertension. Methods and results In 1996, 1638 subjects finished baseline examination, which included anthropometry, blood pressures, CAF, blood biochemistry, plasma insulin, urine examination and electrocardiogram. CAF included standard deviation of normal-to-normal intervals or RR intervals (SDNN), low- and high-frequency power spectrum (LF and HF), and LF/HF ratio at supine for 5 min, the RR interval changes during lying-to-standing maneuver, and the ratio between the longest RR interval during expiration and the shortest RR interval during inspiration (E/I ratio). We used homeostasis model assessment to define beta cell function (HOMA-B) and insulin resistance (HOMA-IR). In total, 992 non-hypertensive participants completed the follow-up assessment in 2003 and 959 participants were included for the final analysis. Incident hypertension was determined by blood pressure status at follow-up. In unadjusted model, both square root of HOMA-IR (OR:3.37, 95%CI: 2.10–6.64) and HOMA-B (OR:0.996, 95%CI: 0.992–0.999) were related to incident hypertension. In multivariate model, square root of HOMA-IR (OR:1.97, 95%CI: 1.05–3.70), but not HOMA-B, was associated with incident hypertension. After further adjustment for baseline CAF, the positive relationship between the square root of HOMA-IR and incident hypertension disappeared. In contrast, LF/HF ratio (OR:1.18, 95%CI: 1.01–1.37), HF power (OR:0.98, 95%CI: 0.96–0.999), and E/I ratio (OR:0.71, 95%CI: 0.54–0.95) were each independently associated with incident hypertension after further adjustment for HOMA measures. Conclusion Sympathovagal imbalance with an apparently decreased parasympathetic tone is an important predictor of incident hypertension independent of IR.

To the Editor: Massive organophosphorus-compound intoxication is relatively common. Although uncommon, delayed neurotoxicity may also occur in humans.1 Persons with organophosphorus-compound poisoning have acute toxic effects, with a cholinergic crisis due to inhibition of acetylcholinesterase. Some persons subsequently have organophosphate-induced delayed neuropathy, which may be related to the inhibition of neurotoxic esterase.2 Organophosphate-induced delayed neuropathy results in damage to both the peripheral and the central nervous systems.3 The exact sequence of lesions in these systems remains controversial, and few reports have discussed central nervous system neuropathological changes in humans. We describe a patient who had a classic acute cholinergic crisis . . .

As very few large scale publications of invasive fungal infection (IFI) have been reported in lupus patients from individual medical centers, a retrospective study was performed from 1988 to 2009 in southern Taiwan. Demographic characteristics, clinical and laboratory data, and mycological examinations were analyzed. Twenty cases with IFI were identified in 2397 patients (0.83% incidence). There were 19 females and one male with an average age of 31.8 ± 12.6. Involved sites included eight disseminated cases, six central nervous system, four lungs, one abdomen and one soft tissue. IFI contributed to a high mortality with 10 deaths (50%), and there were no survivors for the disseminated cases and Candida-infected patients. High activity (Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) > 8) was noted in 50% of IFI episodes. The survival from IFI diagnosis to death was only 7.7 ± 4.2 days, all in a rapid course. No statistical difference was found between survivors and non-survivors when comparing their SLEDAI. Eighty-five percent of IFI episodes under high dosages of corticosteroids therapy and 95% of patients had lupus nephritis. There was an increased risk of IFI in the lupus patients receiving high daily dosage of prednisolone therapy. Critical information from analyses of the present large series could be applied into clinical practices to reduce the morbidity and mortality in such patients.

Background Previous studies on the change of cardiac autonomic function and insulin resistance in metabolic syndrome recruited subjects with cardiovascular-related disease and defined metabolic abnormality with a more severe cutoff. We explored the alteration of cardiac autonomic function and insulin resistance in predisease community dwellers with different numbers of metabolic abnormalities. Methods A total of 1298 subjects were classified as none (n=539), one (n=378), 2 (n=218), and 3 or more metabolic abnormalities (n=154). Insulin resistance was calculated by homeostatic model assessment. Cardiac autonomic function included 5-minute standard deviation of R-R interval, low- and high-frequency power spectrum, and low-/high-frequency power spectrum ratio, the ratio of the longest R-R interval around the 30th beat and the shortest R-R interval around the 15th beat after standing, and the ratio of the longest expiratory R-R interval to the shortest inspiratory R-R interval during deep breathing. Results Subjects with a single metabolic abnormality or more had a lower standard deviation of R-R interval and expiratory/inspiratory ratio than subjects without metabolic abnormality in multivariate analysis. Subjects with 3 or more metabolic abnormalities had a higher low-/high-frequency power spectrum ratio, but a lower high-frequency power. Insulin resistance was higher in groups with 2 metabolic abnormalities or more, but not in the group with one metabolic abnormality, than those without metabolic abnormality. Conclusions Cardiac autonomic function altered in predisease subjects with one or more metabolic abnormalities, while insulin resistance existed in subjects with 2 or more metabolic abnormalities. Thus, autonomic function change may precede insulin resistance in the initiation of metabolic syndrome.

Little is known about the altered cardiac autonomic function (CAF) across different levels of body mass index (BMI), including underweight, normal weight, overweight and obesity. This study provides a thorough analysis to clarify the CAF change in subjects with underweight, overweight and obesity.According to the World Health Organization (WHO) Asia-Pacific BMI cutoffs, a total of 1437 participants were classified as underweight (n=74), normal weight (n=588), overweight (n=313), obesity I (n=390) and obesity II (n=72). CAF was determined by standard deviation of normal-to-normal (SDNN) intervals or RR intervals, power spectrum in low (LF) and high frequency (HF) (LF, 0.04-0.15 Hz; HF, 0.15-0.40 Hz), and LF/HF ratio at supine for 5 min, the ratio between the 30th and the 15th RR interval after standing from the supine position (30/15 ratio) and the average heart-rate change while taking six deep breaths in 1 min (HR(DB)).There were significant differences in age, gender, socioeconomic status, blood pressure, HOMA insulin resistance index, fasting glucose, cholesterol, triglyceride and high-density lipoprotein (HDL)-C, and the prevalence of hypertension, ischemic/left bundle branch block (LBBB) electrocardiography (EKG) pattern, current smoking and alcohol use among subjects with underweight, normal weight, overweight, obesity I and II. Univariate analysis showed that SDNN, HR(DB), HF power and the square root of the LF/HF ratio differed among these five groups. Multivariate analysis showed that obesity I and II were inverse correlates of HR(DB) and HF power. Overweight, obesity I and II were positively associated with the square root of the LF/HF ratio. No BMI status was related to SDNN, 30/15 ratio or LF power. Underweight was not the independent correlate of any CAF indices.The risk for altered CAF is significant in overweight and obese subjects, independent of cardiovascular risk factors. Underweight is not apparently associated with CAF change.

Study design Dermatomal somatosensory-evoked potentials (D-SSEPs) in rats were recorded at the spinal level after L2-, L4-, and L5-dermatome stimulation. Pre- and post-transection patterns and rates of change of corresponding nerve roots were compared to determine accuracy. Objective To investigate characteristics and normal values of D-SSEP elicited from lower limb dermatomes; to determine specificity, sensitivity, and utility of D-SSEP in detecting single-nerve root injury; and to determine optimal stimulation intensity. Summary of background data D-SSEP allows assessment of single nerve root-specific pathways, electrodiagnosis of lumbosacral radiculopathy, and intraoperative neuromonitoring. Unacceptably low sensitivity and specificity make its value suspect. D-SSEP is insufficiently documented. Methods Eight rats were used to specify a standard D-SSEP waveform and its characteristics, evaluate stimulation sites and strengths, and determine appropriate stimulation and recording techniques. The L4 nerve root was transected in one group of 8 rats and the L5 in another. D-SSEPs were recorded at the thoracolumbar junction following submaximal and supramaximal stimulation at the L2, L4, and L5 dermatomal fields. Potentials recorded before transection, and immediately, 1 hour, and 1 week post-transection were compared. Results Reproducible spinal responses were obtained in all rats on all tests. Stimulation intensity, but not rates, affected amplitude. Relative amplitude reductions in transected-root D-SSEP were larger using submaximal than supramaximal intensity. D-SSEP elicited by submaximal than supramaximal intensity produced fewer false negatives and false positives. Conclusions D-SSEP is valuable for detecting acute single nerve root injury. In clinical settings, submaximal dermatomal stimulation identifies conduction abnormalities more consistently and with fewer false negatives and false positives than does supramaximal stimulation. We recommend submaximal stimulation.

The repetitive nerve stimulation test (RNST) has been a useful method in the diagnosis of myasthenia gravis (MG). In clinical practice, a short train of repetitive stimulation is usually given at 3 Hz. Although it was documented that lower stimulation frequencies could offer a greater sensitivity, no study has been done to testify the most sensitive stimulation frequency for RNST. To find out an optimal stimulation frequency, we performed RNST at 0.5, 1, 3, 5, 7, 10, 15 and 20 Hz in 15 MG patients and 5 healthy subjects. The results showed that the decremental response was most often seen at 7 Hz rather than at 3 Hz. To augment the sensitivity in the diagnosis of MG, RNST should be performed stimulation not only at 3Hz but also at other frequencies, preferably 7 Hz.

According to its design concept, a resin-bonded prosthesis, compared with the conventional fixed partial denture, is a weak and unstable structure. Therefore, a resin-bonded prosthesis induces a higher failure rate, especially in the posterior region. Recently, adhesion agents have been profoundly improved. However, the design guidelines of posterior resin-bonded prostheses (RBP) have seldom been evaluated from a biomechanical perspective. The objective of this study was to investigate the biomechanical effects of the retainer thickness on posterior RBP using the finite element method. A solid model of a posterior mandibular resin-bonded prosthesis, which employed the second molar and second premolar as the abutment teeth, was constructed and meshed with various retainer thickness (ranging from 0.2 to 1.0 mm). Horizontal and vertical loadings of 200 N were applied respectively at the central fossa of the pontic to examine the stress level at the interface between the retainer and abutment teeth. All exterior nodes in the root, below the cementoenamel junction were fixed as the boundary condition. The results showed that horizontal loading would induce higher interfacial stresses than the vertical loading which indicated that the horizontal component of the occlusal force plays a more important role in evaluating the debonding phenomenon. Further, the peak interfacial stresses increased as the retainer thickness decreased and, based on the fitted relation between retainer thickness and interfacial stresses, a 0.4 mm retainer thickness was suggested as the minimum required to prevent severe interfacial stresses increasing.

The aim of this research is to apply the surface motor unit action potentials (MUAPs) measured with noninvasive multielectrode for study the motor control ability for paretic limb in stroke patients. To investigate the firing rate variation, the measure of joint interval histogram (JIH), derived from normalized interpulse interval (IPI) train, were adopted in this research. With the limited clinical cases, the JIH parameters are only appropriate for intra-subject comparison for affected and unaffected sides. In addition, MU activities of the affected side measured from acute to stable stages were evaluated for clinical time-course study.

This research studies the feasibility for noninvasive localization of the epileptic foci originating from mesial temporal area. The consistency of foci localization using dipole modelling for varied montages, including standard 10-20, enhanced temporal electrodes, and combination of invasive sphenoid electrode, were investigated. In addition, a 3-D digitizer was utilized to measure the exact positions of electrodes for accurate head geometrical model and better estimation consistency.

A Japanese patient with congenital end-plate acetylcholine esterase (AChE) deficiency developed severe proximal and truncal muscle weakness with preservation of distal strength. Electrophysiological studies included a train of stimuli at 3 HZ, which induced a marked decremental response in the deltoid but not in the first dorsal interosseous (FDI) muscle. Single fiber electromyography (EMG) revealed a high blocking rate (23.1 ± 30.5%, n = 13) with a markedly increased jitter (mean consectuve difference [MCD] 297 ± 218 μs) in the deltoid, but a low blocking rate (6.2 ± 7.4%, n = 16) despite an equally increased jitter (MCD 227 ± 147 μs) in the FDI. In vitro microelectrode study and computer simulation suggested that the combination of a large jitter and a low blocking rate may be ascribed to a reduced end-plate potential (EPP) amplitude with an abnormally prolonged decay time constant (τ). These characteristics may constitute the primary underlying pathophysiologic mechanism in our patient and in similar cases of congenital myasthenic syndrome. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000–000, 2002

A three-phase trial has been done in 11 volunteers. They were given 600 mg phenytoin (Dilantin capsules) in each phase after an overnight fast. In the first study, phenytoin was given alone. In the second phase 400 mg carbamazepine (CBZ) was given at the same time as the phenytoin, and in the third part, 200 mg CBZ t.d.s. was given for one week prior to the phenytoin. Blood samples were taken for 72 h in each phase. Plasma levels of phenytoin and CBZ were determined by HPLC, and plasma protein binding was determined by equilibrium dialysis. The unbound fraction of phenytoin was 0.082, 0.085, and 0.077 in the control, single-dose CBZ, multi-dose CBZ phases, respectively. Single and multiple doses of CBZ decreased the plasma level of phenytoin. The 72-h AUC of phenytoin was 276, 237, and 176 mg h.l-1 in the 3 phases, respectively, and the 72-h AUC of unbound phenytoin was 22.8, 20.5, 13.0 mg h.l-1. The AUC of phenytoin (unbound and total) after multiple doses of CBZ was significantly lower than in the other two phases. The apparent volume of distribution (Vz/f) was 89.9, 110.3, and 121.3 l in the 3 phases, respectively. Through pharmacokinetic analyses, the decreased AUC and increased Vz/f were attributed to decreased bioavailability of phenytoin when CBZ was co-administered.

Analyzing motor unit (MU) activity is essential for studying the neurological dysfunction of upper motor neuron disorders (UMND). This study employs multichannel surface electromyographic (EMG) signals, as recorded from the upper arm during elbow flexion and extension, to analyze the temporal changes and spatial distribution of the dominant firing rate. To estimate the dominant firing rate, the autoregressive (AR) spectrum analysis method is utilized to detect the peaks and poles of the AR model, of the surface EMG spectrum below 40 Hz. The temporal changes in firing rates are also observed by using the spectrogram representation of low-frequency EMG spectra. The EMG spectrogram facilitates examination of the time-varying characteristics of firing rates and recruitment of MUs from surface EMG signal. The low-frequency spectra of multichannel EMG are then represented in a polar form to visualize the spatial distribution of firing patterns across muscles. Via spatio-temporal representation techniques, this study provides a viable approach of observing both the spatial and temporal patterns of MU activities in normal subjects and patients with UMND, including cerebrovascular disease and Parkinson's disease.