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This study investigated whether the individual and combined effects of using biomass energy and living in the neighborhood of a cement plant were associated with the risk of COPD and respiratory symptoms among Congolese women. A total of 235 women from two neighborhood communities of a cement plant participated in this cross-sectional study. Participants were classified into the more exposed group (MEG = 137) and a less exposed group (LEG = 98), as well as into biomass users (wood = 85, charcoal = 49) or electricity users (101 participants). Participants completed a questionnaire including respiratory symptoms, sociodemographic factors, medical history, lifestyle, and household characteristics. In addition to spirometry performance, outdoor PM2.5 (μg/m3) was measured. Afternoon outdoor PM2.5 concentration was significantly higher in MEG than LEG (48.8 (2.5) μg/m3 vs 42.5 (1.5) μg/m3). Compared to electricity users, wood users (aOR: 2.6, 95%CI 1.7; 5.9) and charcoal users (aOR: 2.9, 95%CI 1.4; 10.7) were at risk of developing airflow obstruction. Combined effects of biomass use and living in the neighborhood of a cement plant increased the risk of COPD in both wood users (aOR: 4, 95%CI 1.3; 12.2) and charcoal users (aOR: 3.1, 95%CI 1.7; 11.4). Exposure to biomass energy is associated with an increased risk of COPD. In addition, combined exposure to biomass and living near a cement plant had additive effects on COPD.

Objective Given the recent advent in machine learning and artificial intelligence on medical data analysis, we hypothesized that the deep learning algorithm can classify resting needle electromyography (n-EMG) discharges. Methods Six clinically observed resting n-EMG signals were used as a dataset. The data were converted to Mel-spectrogram. Data augmentation was then applied to the training data. Deep learning algorithms were applied to assess the accuracies of correct classification, with or without the use of pre-trained weights for deep-learning networks. Results While the original data yielded the accuracy up to 0.86 on the test dataset, data-augmentation up to 200,000 training images showed significant increase in the accuracy to 1.0. The use of pre-trained weights (fine tuning) showed greater accuracy than “training from scratch”. Conclusions Resting n-EMG signals were successfully classified by deep-learning algorithm, especially with the use of data augmentation and transfer learning techniques. Significance Computer-aided signal identification of clinical n-EMG testing might be possible by deep-learning algorithms.

Objective To investigate the effect of alpha-linolenic acid-rich diacylglycerol (ALA-DAG) compared with alpha-linolenic acid-rich triacylglycerol (ALA-TAG) on visceral fat area (VFA) in people with overweight. Methods Subjects with overweight were recruited to a randomized, double-blind, controlled, parallel-group designed trial and randomly allocated to two groups that consumed either 2.5 g/d ALA-TAG or ALA-DAG for 12 weeks. Two 4-week nontreatment periods were placed before and after the treatment period. One hundred fourteen subjects (n = 57 in the ALA-TAG group, n = 57 in the ALA-DAG group) were enrolled into the analysis set for efficacy evaluation. Results The VFA and BMI were significantly decreased by the ALA-DAG treatment with a treatment-by-time interaction compared with the ALA-TAG treatment (P

Given the recent technological advent of muscle ultrasound (US), classification of various myopathic conditions could be possible, especially by mathematical analysis of muscular fine structure called texture analysis. We prospectively enrolled patients with three neuromuscular conditions and their lower leg US images were quantitatively analyzed by texture analysis and machine learning methodology in the following subjects : Inclusion body myositis (IBM) [N=11] ; myotonic dystrophy type 1 (DM1) [N=19] ; polymyositis/dermatomyositis (PM-DM) [N=21]. Although three-group analysis achieved up to 58.8% accuracy, two-group analysis of IBM plus PM-DM versus DM1 showed 78.4% accuracy. Despite the small number of subjects, texture analysis of muscle US followed by machine learning might be expected to be useful in identifying myopathic conditions. J. Med. Invest. 66 : 237-240, August, 2019.

This study investigated whether the individual and combined effects of using biomass energy and living in the neighborhood of a cement plant were associated with the risk of COPD and respiratory symptoms among Congolese women. A total of 235 women from two neighborhood communities of a cement plant participated in this cross-sectional study. Participants were classified into the more exposed group (MEG = 137) and a less exposed group (LEG = 98), as well as into biomass users (wood = 85, charcoal = 49) or electricity users (101 participants). Participants completed a questionnaire including respiratory symptoms, sociodemographic factors, medical history, lifestyle, and household characteristics. In addition to spirometry performance, outdoor PM

PMP22 is the most frequent mutated gene in Charcot-Marie-Tooth disease (CMT) type 1A. Another phenotype, hereditary neuropathy with pressure palsies (HNPP), could be caused by PMP22 mutations. PMP22 encodes a peripheral myelin protein with molecular weight 22-kDa. Various pathomechanisms have been postulated in PMP22-related disease, including dysfunction due to missense mutations, and alteration of a gene dose due to duplication/deletion mutations. We identified a novel PMP22 splice site acceptor variant, c.179-1G>A, in a patient with adult-onset chronic generalized polyneuropathy and two asymptomatic family members. Pathophysiological features of the members mainly overlapped with those reported in HNPP, but broad intrafamilial clinical variations were observed. PMP22 transcripts lacking of exon 4 were produced by the variant, presumably leading to in-frame deletion of 47 amino acids. The variant was also shown to exert effect on dosage of PMP22 mRNA. The complex molecular pathology would lead to the unique clinical and pathophysiological conditions.

BACKGROUND AND PURPOSE In myotonic dystrophy type 1 (DM1), weakness of distal limb muscles affects quality of life. Non-invasive evaluation of muscular involvement by muscle sonography could be useful for characterizing muscle-specific involvement. METHODS Sonography of the lower leg and forearm was performed in 19 patients with DM1 and 10 control subjects. The mean echo intensities (EIs) of seven limb muscles were obtained by computer-assisted histogram analysis and compared within DM1 according to the overall clinical severity. RESULTS The EIs of the muscles were significantly higher in DM1 than in the controls (P < 0.01), except for the soleus (P = 0.4). Comparison of adjacent muscles showed the following: (i) greater EIs in flexor digitorum profundus than flexor carpi ulnaris (P < 0.01) and flexor digitorum superficialis (P = 0.02), and (ii) greater EIs in the medial head of the gastrocnemius than the soleus (P < 0.00001). In a subgroup analysis of DM1 according to the modified Rankin Scale (mRS), the more severe subgroup (mRS = 4-5) had lower mean EIs than the less severe subgroup (mRS from 1-3) (P = 0.01) in the flexor digitorum superficialis but not in other muscles. CONCLUSIONS Preferential high echogenicity in the medial gastrocnemius and deep finger flexors is suggestive of DM1. Muscle echogenicity is not generally related to functional dysfunction in DM1.

The chromosomal relationships between the Japanese water shrew Chimarrogale platycephalus and the Eurasian water shrew Neomys fodiens were investigated by conventional and differential staining. From the side-by-side analysis of matching G-banding patterns from the two species, a high degree of G-band homology was recognized in most of the chromosomes that were compared, although the extent of such homology was unclear in several small chromosomes. In C. platycephalus, large blocks of C-heterochromatin (C-blocks) were found in pair nos. M1, M8, M10 and ST23 and in the Y chromosome as conspicuous C-bands, while N. fodiens had no such C-blocks, having centromeric C-bands on most chromosomes with the exception of several small pairs, which included ST1 and ST23. Silver-stained nucleolus organizers (Ag-NORs) were found only on the secondary constriction of pair no. 1 in C. platycephalus and on the minute short arms of ST23 and ST24 in N. fodiens. A discussion of interspecific differences in C-bandin...

The purpose of the present study was to elucidate the relative frequencies of fasciculations assessed by sonography in a large number of muscles in patients with amyotrophic lateral sclerosis (ALS). The patients diagnosed as having ALS were retrospectively assessed by muscle sonography. The frequencies of having fasciculations were compared among the 15 muscles and the subtypes according to the initially affected body region. Overall, approximately half of the muscles had fasciculations (48.8%), in the average of 11.4 muscles per patient. The frequency of fasciculations tended to be lower in the patients with longer disease durations upon testing. Biceps brachii had the highest frequency, followed by extensor digitorum communis, whereas sternocleidomastoid and rectus abdominis had the lowest frequencies. The frequencies of fasciculations were similar among the clinical subtypes. In conclusion, in patients with ALS, fasciculations were detected most frequently in proximal arm muscles by sonography, whereas truncal muscles had lower frequencies. Fasciculations tended to be less evident in the advanced disease stage, possibly reflecting muscle degeneration. Appropriate selection of muscles to observe fasciculations is important for diagnosis of ALS.

Texture analysis characterizes regions in an image by their texture content and has been utilized to infer the underlying structures of medical images such as skeletal muscles. Although potentially useful in tissue diagnosis and assessing disease progression of neuromuscular diseases, the use of texture analysis in such purposes are limited, due to lack of information such as effects of aging. Thus, we performed texture analysis of medial gastrocnemius in healthy individuals form their 20s to late 80s. Among the 283 texture features in 6 classes, the features related to histogram, co-occurrence matrix, absolute gradient, and wavelet were correlated to age in 17-40% of the parameters, while none of the features related to run-length matrix and autoregressive model had significant correlation to age. This study showed that age-dependency in many texture features are present and need to be taken into account in elucidating the clinical significance. By contrast, the features related to run-length matrix and autoregressive model could have clinical utility. J. Med. Invest. 65:274-279, August, 2018.

Objectives The aim of the present study was to investigate the effect of crocetin on sleep architecture and subjective sleep parameters in healthy adult participants with mild sleep complaints. Design A randomized, double-blind, placebo-controlled, crossover study with two intervention periods of 14 days each, separated by a 14-day wash-out period. Interventions Thirty participants were randomly assigned to one of two sequence groups. Each group was given crocetin at 7.5 mg/day, or placebo. We measured objective sleep parameters using single-channel electroencephalography and assessed subjective sleep parameters using the Oguri–Shirakawa–Azumi Sleep Inventory, Middle-age and Aged version (OSA-MA). Main outcome measures Differences between crocetin and placebo in an objective sleep parameter (delta power), and OSA-MA scores. Results Delta power was significantly increased with crocetin compared with placebo. There were no significant differences in the other sleep parameters, including sleep latency, sleep efficiency, total sleep time, and wake after sleep onset. Subjective scores for sleepiness on rising and feeling refreshed were significantly improved with crocetin compared with placebo. Conclusions The findings of the present study suggest that crocetin supplementation contributes to sleep maintenance, leading to improved subjective sleep quality.

The diagnostic importance of audio signal characteristics in needle electromyography (EMG) is well established. Given the recent advent of audio-sound identification by artificial intelligence, we hypothesized that the extraction of characteristic resting EMG signals and application of machine learning algorithms could help classify various EMG discharges.Data files of 6 classes of resting EMG signals were divided into 2-s segments. Extraction of characteristic features (384 and 4,367 features each) was used to classify the 6 types of discharges using machine learning algorithms.Across 841 audio files, the best overall accuracy of 90.4% was observed for the smaller feature set. Among the feature classes, mel-frequency cepstral coefficients (MFCC)-related features were useful in correct classification.We showed that needle EMG resting signals were satisfactorily classifiable by the combination of feature extraction and machine learning, and this can be applied to clinical settings. Muscle Nerve 59:224-228, 2019.

Background and purpose Differential diagnosis of sporadic inclusion body myositis (s-IBM) and polymyositis (PM)/dermatomyositis (DM) is difficult and can affect proper disease management. Detection of heterogeneous muscular involvement in s-IBM by muscle sonography could be a unique diagnostic feature. Methods Sonography of the lower leg and forearm was performed in patients with s-IBM, PM/DM and control subjects (n = 11 each). Echo intensities (EIs) of the adjacent muscles [medial head of the gastrocnemius versus soleus and the flexor digitorum profundus (FDP) versus flexor carpi ulnaris (FCU)] were scored by three blinded raters. The mean EIs of these muscles were compared using computer-assisted histogram analysis. Results Both evaluation methods showed high echoic signals in the gastrocnemius of patients with s-IBM. EIs were significantly different between the gastrocnemius and soleus in patients with s-IBM, but not in those with DM/PM and the controls. In the forearm, although the EI of the FDP was higher in the s-IBM group than in the other groups, the EI differences between the FDP and FCU did not differ significantly between disease groups. The difference in area under the curves to differentiate between s-IBM and DM/PM was greatest between the gastrocnemius−soleus EIs (0.843; P = 0.006). Conclusions High echoic signals in the medial gastrocnemius compared with those of the soleus are suggestive of s-IBM over PM/DM.

Objective To elucidate the mechanism of focal conduction slowing in the median nerve in ALS. Methods The patients with ALS and CTS and normal control subjects were tested with sonography of the median and ulnar nerves. The cross-sectional areas (CSAs) and the wrist–forearm CSA ratios were compared with the parameters of nerve conduction study. Results The median motor distal latency was frequently prolonged in ALS and CTS. CSA and the wrist–forearm ratio of the median nerve were smaller in ALS than in CTS. The ulnar nerve sonography was similar in all the groups. Conclusions Selective conduction slowing of the median nerve at the wrist in ALS is unlikely due to secondary compressive neuropathy, as seen in carpal tunnel syndrome. Significance Unique vulnerability of the median nerve in ALS may explain the selective conduction slowing.

Objectives/Hypothesis The etiology of Ramsay Hunt syndrome (Hunt syndrome) is reactivation of latent varicella-zoster virus (VZV) in the geniculate ganglion of the facial nerve, leading to neuritis. Although the mechanism of the VZV reactivation is unclear, one possibility is that the reactivation involves a low level of VZV-specific cell-mediated immunity (CMI). The aim of this study was to clarify the characteristics of the VZV-specific CMI in Hunt syndrome compared to that in Bell's palsy, and to obtain clues to its role in the development of Hunt syndrome. Study Design Prospective study. Methods We determined the median spot numbers and examined VZV-specific CMI in patients with Hunt syndrome and with Bell's palsy using interferon-γ enzyme-linked immunospot (ELISPOT) assays. We analyzed the relationship between the value of VZV-specific CMI and days from disease onset. Results The median spot number in Hunt syndrome (87.3 spot-forming cells [SFCs]/4 × 105 peripheral blood mononuclear cells [PBMCs]) was higher than that in Bell's palsy (62.3 SFCs/4 × 105 PBMCs). Hunt syndrome showed a strong relationship between the ELISPOT count and days from onset (r = 0.65). Within the first 5 days from onset, no ELISPOT counts higher than 80 SFCs/4 × 105 PBMCs were observed. On the other hand, no correlation was observed between the ELISPOT count and days from onset in patients with Bell's palsy (r = −0.19). Conclusions These results suggest that VZV-specific CMI in Hunt syndrome is low at disease onset and increases rapidly thereafter. Consequently, reduced VZV-specific CMI may play an important role in the reactivation of VZV in the facial nerve, leading to Hunt syndrome. Level of Evidence 4 Laryngoscope, 126:E35–E39, 2016

Vasa nervorum is a collective term for a complex microcirculation that provides nutrients to peripheral nerves. Vasa nervorum is known to be disturbed in diabetic neuropathy, mononeuritis multiplex, vasculitic neuropathy and few cases of facial nerve paralysis.1 Sonography has been used to detect focally increased intraneural blood flow in carpal tunnel syndrome.2 In neurolymphomatosis, enlarged nerves showed qualitatively increased blood flow within the area of thickening.3 Similar findings of increased blood flow signals were observed in leprosy.4 As inflammatory vasodilation increases intraneural blood flow in an acute postdenervation period,5 we hypothesised that intraneural blood flow in inflammatory neuropathies becomes abnormal, by employing a quantitative method. We conducted a prospective study from June 2015 to December 2015. Institutional Review Board approved this study. The participants signed a written consent. The first group was the control group, which includes healthy non-smoking participants without clinical signs by neurological examination or symptoms of a neurological disease, no known comorbidities such as hypertension, dyslipidaemia and diabetes mellitus and without a history of traumatic injuries. The second group was the inflammatory neuropathy group, which includes participants diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP), Guillain-Barre syndrome (GBS) and multifocal motor neuropathy (MMN). The third was grouped as other peripheral nerve diseases as disease control, which includes participants diagnosed with amyotrophic lateral sclerosis (ALS) and Charcot-Marie-Tooth Disease type 1A …

Charcot-Marie-Tooth disease (CMT) is a hereditary peripheral neuropathy characterised by length-dependent degeneration of the motor and sensory nerve fibres with consequent distal muscle weakness, atrophy and mild sensory loss, primarily in lower limbs. The historic prevalence of CMT in the general population is 1 in 2500 individuals,1 while the present prevalence is 1 in 1214 individuals.2 Missense mutations in the mitofusion 2 gene ( MFN2 ; OMIM*608506) have been found in most axonal forms (CMT type 2; CMT2) with autosomal dominant inheritance, and truncation mutations can be found in a few cases with seemingly autosomal recessive inheritance or sporadic cases. A dominant negative or toxic gain-of-function mechanism has been postulated in the autosomal dominant mode; however, the biological effect(s) by mutant MFN2 may vary depending on the nature of the mutations.3 This report describes a unique pathomechanism identified in a large Japanese MFN2 -CMT2A2 family. The currently living family members were examined by movement disorder specialists (TK, RM, HN, YN and YI). Neurological assessments, including the Charcot-Marie-Tooth disease neuropathy score V.2, electrophysiology of peripheral nerves and neuroimaging analyses, were carried out. Genetic analyses were conducted as described in online supplementary data, including targeted resequencing, Sanger sequencing, restriction fragment length polymorphism (RFLP) analysis and semiquantitative reverse-transcription (RT)-PCR. Peripheral T-cells were cultured with a nonsense-mediated decay (NMD) inhibitor, emetine, in order to evaluate the effect by NMD system. A bioinformatic analysis and literature review were also carried out. The details are described in online supplementary data. ### Supplementary data [jnnp-2015-312646supp.pdf] The family is composed of a three-generation kindred, with autosomal dominant inheritance (figure 1A). Nine individuals were diagnosed as ‘certainly affected’ and classified as having Charcot-Marie-Tooth disease. Clinical and laboratory features of all affected individuals are summarised in online supplementary tables S1 and S2, and figure S1. Age-at-onset was 5 or …

Purpose To assess the multiple texture features of skeletal muscles in neurogenic and myogenic diseases by using ultrasonography (US). Materials and Methods After institutional review board approval, muscle US studies of the medial head of the gastrocnemius were performed prospectively in patients with neurogenic diseases (n = 25 [18 men]; mean age, 66.0 years ± 12.3 [standard deviation]), in patients with myogenic diseases (n = 21 [12 men]; mean age, 68.3 years ± 11.5), and in healthy control subjects (n = 21 [11 men]; mean age, 70.5 years ± 8.4) between January 2013 and May 2016. Written informed consent was obtained. Muscle texture parameters were obtained, and five algorithms were used to classify the groups. Results The neurogenic and myogenic disease groups showed higher echo intensities than the control subjects. The histogram-derived texture parameters had overlaps between the neurogenic and myogenic groups and thus had a low discrimination rate. With assessment of more classes of texture parameters, three groups were correctly classified (100% correct, according to four of five classification algorithms). Tenfold cross validation showed 93.5%-95.7% correct classification between the neurogenic and myogenic groups. The run-length matrix, autoregressive model, and co-occurrence matrix were particularly useful in distinguishing the neurogenic and myogenic groups. Conclusion Texture analysis of muscle US data can enable differentiation between neurogenic and myogenic diseases and is useful in noninvasively assessing underlying disease mechanisms. © RSNA, 2017 Online supplemental material is available for this article.

Morphological assessment of peripheral nerves in amyotrophic lateral sclerosis (ALS) has been available by sonography. Detection of possible axonal atrophy could be important in predicting progression. Research on correlation between sonographic findings and clinical presentation has been sparse. The aim of the study was to assess possible motor axon loss in patients with ALS by sonography and to correlate the imaging features with clinical subtypes. Patients with either definite or probable ALS and control subjects had sonographic evaluation of the cervical nerve roots (C5, C6, and C7). Each diameter and their sums were measured. The ALS patients were classified by their clinical onset and progression (arm-onset, leg-onset, bulbar, and flail-arm variant) and the sonographic features were compared. Overall, the cervical nerve roots were thinner in ALS than in the controls, but the diagnostic sensitivity was low. The patients with arm dysfunctions tended to show thinner nerve roots than those with normal or relatively preserved arm functions. The four ALS subtypes showed similar diameters of the nerve roots. There was no correlation between the disease duration and the diameters of the nerve roots. Sonography of the cervical nerve roots showed axonal atrophy in ALS and potentially reflects subtle arm dysfunctions.

This study aimed to characterize the excitability changes in peripheral motor axons caused by hindlimb unloading, which is a model of disuse neuromuscular atrophy. Hindlimb unloading was performed in normal 6-week-old male mice by fixing the proximal tail by a clip connected to the top of the animal’s cage for 3 weeks. Axonal excitability studies were performed by stimulating the sciatic nerve at the ankle and recording the compound muscle action potential from the foot. The amplitudes of the motor responses of the unloading group were 51% of the control amplitudes (2.2 ± 1.3 mV [HLU] vs. 4.3 ± 1.2 mV [Control], P = 0.03). Multiple axonal excitability analysis showed that the unloading group had a smaller strength-duration time constant (SDTC) and late subexcitability (recovery cycle) than the controls (0.075 ± 0.01 [HLU] vs. 0.12 ± 0.01 [Control], P < 0.01; 5.4 ± 1.0 [HLU] vs. 10.0 ± 1.3 % [Control], P = 0.01, respectively). Three weeks after releasing from HLU, the SDTC became comparable to the control range. Using a modeling study, the observed differences in the waveforms could be explained by reduced persistent Na+ currents along with parameters related to current leakage. Quantification of RNA of a SCA1A gene coding a voltage-gated Na+ channel tended to be decreased in the sciatic nerve in HLU. The present study suggested that axonal ion currents are altered in vivo by hindlimb unloading. It is still undetermined whether the dysfunctional axonal ion currents have any pathogenicity on neuromuscular atrophy or are the results of neural plasticity by atrophy.

The midline electroneurography (ENoG) method might reflect total facial nerve degeneration.We compared ENoG values in patients with facial palsy using two different methods, the midline method and five electroneurogram recordings, to reveal whether the ENoG value obtained with the midline method reflects total facial nerve degeneration.Forty patients with facial palsy were enrolled. Compound muscle action potentials (CMAPs) were recorded using the midline method, in which the anode was placed on the mental protuberance and the cathode was placed on the philtrum. Additionally, five electroneurogram recordings were obtained by placing the anode on the skin of the parietal region and five cathodes on the skin over five facial muscles (frontalis, orbicularis oculi, nasalis, orbicularis oris, and depressor anguli oris muscles). ENoG values recorded using the two methods were compared.The ENoG values of the five facial muscles did not differ from those obtained using the midline method. The total ENoG value calculated by summing five CMAPs from five facial muscles, which is considered to reflect total facial nerve degeneration, was not significantly different from that using midline methods; moreover, a strong positive correlation coefficient (r = 0.87) was found between them.

Muscle sonography may show high densities in various myopathic conditions. Further classification among myopathic conditions could be possible by texture analysis, which analyzes relationships between the neighboring pixel densities. The following groups of subjects were assessed: (1) 19 patients with myotonic dystrophy type 1 (MD1), (2) 11 patients with inflammatory myopathy (IM), and (3) 16 normal control. A LOGIQe ultrasonography and an 11-MHz linear probe were used to obtain muscle images of medial gastrocnemius. Texture parameters were obtained by MaZda software. Linear Discriminant Analysis (LDA) was performed for texture-based classification. The mean echodensities of MD1 and IM were higher than those of the control, which yielded high areas under curve (AUC) >0.95. However, MD1 and IM were poorly discriminated by any of the histogram-related parameters (AUC

Takotsubo syndrome (TTS) is an acute cardiac syndrome characterized by regional left ventricular dysfunction with a peculiar circumferential pattern, which typically results in apical ballooning. Evidence indicates a pivotal role of catecholamines in TTS, and researchers have discussed multiple hypotheses on the etiology, including multivessel coronary spasm, myocardial stunning, excessive transient ventricular afterload, and cardiac sympathetic overactivity with local noradrenaline spillover. Although central nervous system disorders, such as stroke and epilepsy, are known to trigger TTS, the incidence and clinical features of TTS in neurodegenerative disorders are poorly understood. Here, we retrospectively examined TTS cases in a single-center cohort composed of 250 patients with amyotrophic lateral sclerosis (ALS) and 870 patients with synucleinopathies [582 patients with Parkinson's disease (PD), 125 patients with dementia with Lewy bodies (DLB), and 163 patients with multiple system atrophy (MSA)] and identified 4 (1.6%, including 2 women) cases with ALS and no cases with synucleinopathies. Two ALS patients underwent autopsy and the pathological findings were compatible with the chronological changes identified in catecholamine-induced cardiomyopathy. A literature review identified 16 TTS cases with ALS, 1 case each with PD and DLB, and no cases with MSA. When current and previous TTS cases with ALS were concatenated: 55% (11/20) were female; 35% (7/20) had a bulbar-onset and 45% (9/20) had a limb-onset; the mean age of TTS onset was 63.3 ± 9.0 years and the mean interval time from ALS onset to TTS development was 4.9 ± 3.0 years; no (0/16) patients developed TTS within 12 months after ALS onset; 50% (10/20) underwent artificial ventilations; the mortality was 17% (3/18); and most cases had precipitating factors, and TTS development was associated with gastrostomy, tracheostomy, or infections in 45% (9/20) of the patients. This study demonstrated that ALS is a considerable predisposing factor of TTS and that synucleinopathies rarely cause TTS. The distinct TTS incidence between ALS and synucleinopathies may be due to cardiac sympathetic overactivity in ALS and may also be affected by cardiac sympathetic denervation in synucleinopathies. Moreover, the etiology of TTS in ALS may be reasonably explained by the two-hit theory.

Threshold tracking testing has provided novel insights of peripheral nerve excitability in normal and pathologic conditions. However, little has been known on the nerve excitability properties of axons with different stimulation thresholds and the effects of aging and peripheral neuropathy to those. We performed multiple nerve excitability tests in normal controls divided into three age groups and in patients with diabetic neuropathy, which were recorded at three target levels (10%, 40%, and 60% of the maximum motor response amplitudes). In all the control groups, tracking at low target level shows smaller threshold change by hyperpolarizing stimuli and greater threshold change by depolarizing stimuli, suggestive of greater transient Na current. Normal elderly showed greater threshold change by hyperpolarizing pulse than younger subjects at high target level, likely reflecting decrease of axon diameters. Patients with diabetic neuropathy showed smaller threshold changes by both depolarizing and hyperpolarizing pulses ("fanning-in"), more noticeably at the lower target level, suggestive of the combined effects of membrane depolarization and greater decrease of axonal diameters in smaller fibers. Given the reported unpredictable electrical recruitment order in the diseased conditions and difference of nerve excitability measures in threshold electrotonus at different target levels, comparing threshold electrotonus values between normal and diseased axons may be problematic by comparing axons with different nerve excitability characteristics.

Antiphospholipid antibody syndrome (APS) has been widely recognized to be associated with various neurological complications. In addition to the classical notion of APS as a thrombotic disorder, APS has been suggested to be an autoinflammatory disease as well. We present a previously healthy 46-year-old man who concurrently developed transverse myelitis and polymyositis whose laboratory studies were significant for the elevated antiphospholipid antibodies such as anti-cardiolipin (CL)/beta2-glycoprotein I (beta 2GPI) antibody. This report further enhances the recognized clinical phenotypes of the neurological complications of APS and the understanding of its pathomechanism.

Cystic lymphangioma, a vascular anomaly considered to be a lymph sac derived from the fetal jugular vein remaining as a mass, is frequently noted in the lateral natal neck. It is classified as a vascular malformation by the International Society for the Study of Vascular Anomalies (ISSVA). While most cases are asymptomatic, it may grow into an unwieldy mass. We report a case of cystic lymphangioma and abnormal subclavian vein distribution incidentally identified during trauma treatment. A 2-year-old boy, with left supraclavicular fossa swelling, had fallen from a 120 cm height in a park and struck his left shoulder, which was left untreated due to the absence of pain. His family noted a slowly growing left supraclavicular fossa mass the following day. When first seen, he had a 30×40 mm mass in the left supraclavicular fossa. Palpation indicated a smooth, slightly soft, undulating, surface a cystic lesion containing a septum. Computed tomography (CT), magnetic resonance imaging (MRI), ultra sonography (US) needle aspirate of the cyst was bloody and malformation of the left subclavian vein distributing in the left supraclavicular region was noted. The mass was excised due to its rapid growth, together with part of the platysma muscle to which the mass strongly adhered. The two blood vessels entering the mass, were ligated and excised en bloc with the mass, which was diagnosed pathologically as cystic lymphangioma. No recurrence has occurred in the 4 years since surgery.

Objectives/Hypothesis: We present the case of a 21-year-old woman who underwent endoscopy-assisted surgery with topical mitomycin for a large cholesterol granuloma in the petrous apex that involved the eustachian tube. Study Design: Case report. Methods: Minimally invasive surgery was performed on the cholesterol granuloma with endoscopic assistance, and topical mitomycin (0.4 mg/mL) was administered to prevent scarring of the newly created drainage/ventilation route. With the endoscopic approach, the drainage/ventilation route was secured not only from the tympanic cavity, but also using a guidewire inserted from the pharyngeal orifice of the eustachian tube. Results: The drainage/ventilation route between the nasopharynx and middle ear cavity involving the cholesterol granuloma has been preserved more than for 9 months postoperatively. Her hearing has recovered. Conclusions: This less invasive technique is a surgical option for patients with a large cholesterol granuloma in the petrous apex involving the eustachian tube. Laryngoscope, 2009

Background Sonography of peripheral nerves can depict alteration of nerve sizes that could reflect inflammation and edema in inflammatory and demyelinating neuropathies. Guillain-Barre syndrome (GBS). Information on sonographic comparison of an axonal subtype (acute motor [and sensory] axonal neuropathy [AMAN and AMSAN]) and a demyelinating subtype (acute inflammatory demyelinating polyneuropathy [AIDP]) has been sparse. Material and Methods Sonography of peripheral nerves and cervical nerve roots were prospectively recorded in patients with GBS who were within three weeks of disease onset. Results Five patients with AIDP and nine with AMAN (n = 6)/AMSAN (n = 3) were enrolled. The patients with AIDP showed evidence of greater degrees of demyelination (e.g., slower conduction velocities and increased distal latencies) than those with AMAN/AMSAN. The patients with AIDP tended to show enlarged nerves in the proximal segments and in the cervical roots, whereas the patients with AMAN/AMSAN had greater enlargement in the distal neve segment, especially in the median nerve ( P = 0.03; Wrist-axilla cross-sectional ratio). Conclusion In this small study, two subtypes of GBS showed different patterns of involvement that might reflect different pathomechanisms.

Serial recordings were performed to measure sensory excitability in peripheral nerves and elucidate age-dependent changes in neuronal ion currents in the peripheral sensory nervous system. The threshold tracking technique was used to measure multiple excitability indices in the tail sensory nerves of five normal male mice at four time points (6, 10, 14, and 19 weeks of age). A separate group of four mice was also measured at 43 weeks and at 60 weeks of age. Maturation was accompanied by an increase in early hyperpolarization and superexcitability at 10 weeks. At 60 weeks, the hyperpolarizing electrotonus shifted downward, while superexcitability became greater and subexcitability (double stimuli) decreased. Computer modeling showed that the most notable age-related interval changes in excitability parameters were Barrett-Barrett, H, and slow K(+) conductances. Understanding age-related changes in the excitability of sensory axons may provide a platform for understanding age-dependent sensory symptoms and developing age-specific channel-targeting therapies.

The etiology of Ramsay Hunt syndrome (Hunt syndrome) is reactivation of latent varicella-zoster virus (VZV) in the geniculate ganglion of the facial nerve, leading to neuritis. Although the mechanism of the VZV reactivation is unclear, one possibility is that the reactivation involves a low level of VZV-specific cell-mediated immunity (CMI). The aim of this study was to clarify the characteristics of the VZV-specific CMI in Hunt syndrome compared to that in Bell's palsy, and to obtain clues to its role in the development of Hunt syndrome.Prospective study.We determined the median spot numbers and examined VZV-specific CMI in patients with Hunt syndrome and with Bell's palsy using interferon-γ enzyme-linked immunospot (ELISPOT) assays. We analyzed the relationship between the value of VZV-specific CMI and days from disease onset.The median spot number in Hunt syndrome (87.3 spot-forming cells [SFCs]/4 × 10(5) peripheral blood mononuclear cells [PBMCs]) was higher than that in Bell's palsy (62.3 SFCs/4 × 10(5) PBMCs). Hunt syndrome showed a strong relationship between the ELISPOT count and days from onset (r = 0.65). Within the first 5 days from onset, no ELISPOT counts higher than 80 SFCs/4 × 10(5) PBMCs were observed. On the other hand, no correlation was observed between the ELISPOT count and days from onset in patients with Bell's palsy (r = -0.19).These results suggest that VZV-specific CMI in Hunt syndrome is low at disease onset and increases rapidly thereafter. Consequently, reduced VZV-specific CMI may play an important role in the reactivation of VZV in the facial nerve, leading to Hunt syndrome.

We identified a novel homozygous mutation in the splice site donor (SSD) of intron 30 (c.5866 + 1G > A) in consanguineous Japanese SPG11 siblings showing late-onset spastic paraplegia using the whole-exome sequencing. Phenotypic variability was observed, including age-at-onset, dysarthria and pes cavus. Coding DNA sequencing revealed that the mutation affected the recognition of the constitutive SSD of intron 30, splicing upstream onto a nearby cryptic SSD in exon 30. The use of constitutive splice sites of intron 29 was confirmed by sequencing. The mutant transcripts are mostly subject to degradation by the nonsense-mediated mRNA decay system. SPG11 transcripts, escaping from the nonsense-mediated mRNA decay pathway, would generate a truncated protein (p.Tyr1900Phefs5X) containing the first 1899 amino acids and followed by 4 aberrant amino acids. This study showed a successful clinical application of whole-exome sequencing in spastic paraplegia and demonstrated a further evidence of allelic heterogeneity in SPG11. The confirmation of aberrant transcript by splice site mutation is a prerequisite for a more precise molecular diagnosis.

We present a patient who initially developed diffuse painful muscle cramps who had elevated antibodies against voltage-gated potassium channel (VGKC) complex. Despite the initial improvement after immunomodulatory therapy, she later developed progressive atrophy and weakness of the limb muscles whose electrophysiological finding mimicked that in lower motor neuron disease. A potential causal relationship between anti-VGKC complex antibody-associated hyperexcitability and lower motor axon loss is discussed.

Objectives:(1) Compare longitudinal changes of Varicella-zoster virus (VZV)-specific cell-mediated immunity (CMI) in Hunt syndrome with Bell’s palsy using IFN-γ enzyme-linked immunospot (ELISPOT). (2) Examine the role of VZV-specific CMI for VZV reactivation in the facial nerve in Hunt syndrome.Methods:This prospective study was conducted in our tertiary referral hospital between 2010 and 2013. Nineteen Hunt syndrome and 59 Bell’s palsy patients were enrolled. Mononuclear cells isolated from whole blood were incubated with VZV antigen in culture plates for 40 hours. Anti IFN-γ antibody was added and the ELISPOT system counted immunostained spots indicating VZV-specific CMI. The relationship between the spots and days from the onset of palsy were compared between Hunt syndrome and Bell’s palsy patients.Results:Immediately after the onset, the number of spots in the Hunt syndrome group was much lower than in the Bell’s palsy group, indicating low VZV-specific CMI. However, it increased rapidly and showed a ...

Objectives:(1) Estimate the degree of postoperative aeration in the middle ear after canal wall down tympanoplasty with soft-wall reconstruction (CWD tympanoplasty with SWR) for cholesteatoma. (2) Characterize the relationship between postoperative middle ear aeration and hearing outcome. (3) Propose an ideal state of middle ear aeration in order to obtain satisfactory hearing outcome after CWD tympanoplasty with SWR.Methods:This retrospective study was conducted in our tertiary referral hospital between 2001 and 2013. Seventy-eight ears with cholesteatoma treated surgically at our hospital by planned two-stage CWD tympanoplasty and SWR were included. Postoperative middle ear aeration was scored one year after second-stage surgery by computed tomography (CT). The patients were divided into 4 bins according to postoperative audiometric air-bone (A-B) gaps: 0-10, 11-20, 21-30, and >30 dB.Results:Postoperative middle ear aeration was significantly greater in the smaller A-B gap bins (0-10 and 11-20 dB) compa...

Objective The objective was to study the in vivo effects of anesthetic agents on peripheral nerve excitability. Methods Normal male mice were anesthetized by either isoflurane inhalation or a combination of medetomidine, midazolam, and butorphanol intraperitoneal injection (“triple agents”). Immediately after induction, the tail sensory nerve action potential was recorded and its excitability was monitored. Results Under both anesthetic protocols, there was an interval excitability change by long hyperpolarizing currents. There was greater threshold reduction approximately 30 min post induction, in comparison to immediately post induction. Other excitability parameters were stable over time. Modeling suggested interval suppression of internodal H conductance or leak current. Conclusions Anesthetic agents affected responses to long hyperpolarizing currents. Significance Axonal excitability during intraoperative monitoring may be affected by anesthetic agents. Interpretation of interval excitability changes under anesthesia requires caution, especially with long hyperpolarizing currents.

The imaging of muscle fibers has been utilized in the management of patients with suspected myopathy. Ultrasonography (US) of skeletal muscles has advantages over MRI and CT in that US can quickly assess muscles in the entire body. US findings in myopathy are diffuse (e.g., increased or decreased echo signal in muscular dystrophy and myositis) and focal (e.g., a mass in sarcoid myopathy, or preferential involvement in inclusion body myositis). US evaluation is useful in determining the potential site for a muscle biopsy, where an adequate degree of myopathy should be present. Further studies will reveal the correlation between the sonographic findings as well as clinical and other imaging abnormalities.

The satellite images of volcanic clouds in Kyushu, Japan during September–November 1989 were studied in connection with the mountain site measurement of atmospheric qualities at Unzen-Nodake and the SO2 concentration data at Aso Volcano Museum. The images strongly indicate that many high concentration events of SO2 were the results of the long-range transport of volcanic gas from Mt. Aso and Mt. Sakurajima to these stations. Brief comments on the 2000 eruption of Miyake-jima volcano are added.

Wet-only event-basis precipitation data at Nagasaki, the border area between the Asian Continent and Japan, with high non-sea-salt (nss-) SO 2- 4 and NO - 3 concentrations from November 1983 through March 1988 were analyzed in terms of wind conditions at upper and surface levels to assess both long-distant and local sources. In order to investigate the high nss-SO 2- 4 concentration events occurring with similar transport patterns, the wind conditions were grouped into the following three types: type 1, the upper air flow from the Asian Continent and the surface wind from the sea; type 2, the stagnant upper air and the surface wind from the land at and around Nagasaki; and type 3, the upper air flow from the Continent and the surface wind from the land. In the case of high NO - 3 concentration events, their wind-condition types were similar to those for high nss-SO 2- 4 concentration events. These three types for both ions were discussed to estimate their sources as follows: type 1, long-distant sources in the Asian Continent; type 2, local sources at and around Nagasaki; and type 3, both long-distant and local sources. From the viewpoint of precipitation chemistry, the ratios of H + /(nss-SO 2- 4 +NO - 3 ) were evaluated for the high concentration events so as to examine the degree of neutralization of acidic input, H 2 SO 4 and HNO 3 . High ratios events corresponded to wind-condition type 2 whereas low ratios were associated with types 1. This suggested that the acidic input from local sources were little neutralized to cause much higher acidity in precipitation than those from long-distant sources.

The IgG1 mouse monoclonal antibody (MAb) KHRI-3, binds to an antigen of 65–68 kDa expressed on inner ear supporting cells in guinea pigs. We previously showed [Nair et al. (1995) Monoclonal antibody induced hearing loss. Hear. Res. 83, 101–113] that mice carrying the KHRI-3 hybridoma develop high frequency hearing loss and loss of hair cells in the basal turn suggesting that this MAb causes immune-mediated sensorineural hearing loss. To evaluate the specificity of this effect, sterile KHRI-3 and control IgG1 preparations were infused directly into the guinea pig cochlea using Alzet® mini-osmotic pumps. Assessments included: (1) hearing, measured by click auditory brain stem responses (ABRs); (2) in vivo antibody binding; and (3) the structural integrity of the organ of Corti. Nine animals were infused with KHRI-3 preparations and 5 controls were infused with control IgG1. Four guinea pigs given KHRI-3 developed 25–55 dB hearing loss. Control animals showed no difference from baseline. In vivo binding of KHRI-3 was detected in the organ of Corti in 6 of the 9 animals, including all 4 that had hearing loss. No staining was observed with control antibody. Confocal microscopy revealed that the in vivo KHRI-3 antibody binding pattern was identical to that obtained by incubating fixed tissue in vitro with KHRI-3. Histologic examination revealed an increased frequency of hair cell loss in KHRI-3 treated ears when compared to either the contralateral ears of the same guinea pigs or the IgG1 treated ears of control animals. The lesions in the infused ears of guinea pigs were scattered throughout the cochlea from base to apex. These experiments demonstrate the following points: (1) Antibodies can be chronically infused directly into the cochlea of living animals. (2) The KHRI-3 antibody binds to live supporting cells within the organ of Corti. (3) Infusion of an inner ear specific antibody affects auditory function. (4) The infusion of irrelevant antibody had no effect on the structure or function of the ear. This system provides an animal model for further studies of antibody-induced sensorineural hearing loss.

Precipitation pH was automatically measured on site for each 0.5 mm-rainfall sample at 29 nationwide stations in Japan in Phase-II of Acid Deposition Survey from 1989 FY to 1992 FY by Japan Environment Agency. The mean pH of all of the stations over the entire survey period was pH 4.6. There was no pH record less than pH 3.0 which was supposed to affect plant growth. In western Japan and in remote islands in the Sea of Japan, lower pH was observed than in the other regions. Regarding seasonal variations, pH was rather lower in winter and spring. The mean pH of initial 0.5 mm-rainfall was lower than that of the whole rainfall at many stations, although it was higher at 8 stations. The monthly means of pH based on the automatic measurements of 0.5 mm-rainfall samples were compared with those from the manual measurements of biweekly samples, showing that the automatically determined pH was lower than the manually determined one by 0.3 pH unit on average. One of the possible causes of this pH difference is solution of alkali particles in the stored samples.

Objective Progressive atrophy and loss of motor axons is a hallmark of amyotrophic lateral sclerosis (ALS). Limited sonographic data are available on potential detection of atrophy of peripheral nerves and nerve roots in ALS. Methods Patients with either definite or probable ALS and control subjects underwent sonographic evaluation of the cervical roots (C5, C6, and C7) and peripheral nerves (median and ulnar nerves) on the right. These diameters and cross-sectional areas (C6, median, and ulnar nerves) were compared. Results The diameters and cross-sectional areas were consistently smaller in ALS than in controls. No correlation was present between the sonographic parameters and the disease severity, disease duration, age, or gender. The overall sensitivity and specificity tended to be greater in the cervical nerve roots than in the peripheral nerves. Conclusions This study shows atrophy of cervical nerve roots and peripheral nerves in ALS detected by sonography. Cervical nerve roots might be more appropriate to detect motor axon loss than peripheral nerves. Significance Sonographic evaluation of nerve roots and peripheral nerves may be a useful disease marker in ALS to confirm the diagnosis and to potentially monitor the disease progression.

Objectives:1) Compare electroneuronography (ENoG) values in patients with facial palsy using two different methods, the midline method that records compound muscle action potentials (CMAPs) from the orbicularis oris muscle (the standard muscle for facial ENoG) and five electroneurogram recordings that records five CMAPs from five different facial muscles. 2) Reveal whether the ENoG value obtained with the midline method reflects entire facial nerve degeneration.Methods:Forty patients with facial palsy were enrolled. CMAPs were recorded using the midline method, in which the anode was placed on the mental protuberance and the cathode was placed on the philtrum. Additionally, five electroneurogram recordings were obtained by placing the anode on the skin of the parietal region and five cathodes on the skin over five facial muscles (frontalis, orbicularis oculi, nasalis, orbicularis oris, and depressor anguli oris muscles). ENoG values recorded using the two methods were compared.Results:The ENoG values of t...

Objectives:1) Compare Varicella-zoster virus (VZV)-specific cell-mediated immunity (CMI) in Hunt syndrome to Bell’s palsy using IFN enzyme-linked immunospot (ELISPOT). 2) Examine the role of VZV-specific CMI for VZV reactivation in the facial nerve in Hunt syndrome.Methods:This prospective study was conducted in our tertiary referral hospital between 2010 and 2012. Six Hunt syndrome and 28 Bell’s palsy patients were enrolled. Mononuclear cells were isolated from whole blood and incubated with VZV antigen in culture plates for 40 h. Anti IFN antibody was added and the ELISPOT system counted immunostained spots indicating VZV-specific CMI. Numbers of spots and the relationship between the spots and days from the onset of palsy were compared between Hunt syndrome and Bell’s palsy patients.Results:No difference in the number of spots was observed between Hunt syndrome and Bell’s palsy. However, Hunt syndrome showed a strong positive relationship between numbers of spots and days from the onset of palsy (r = 0...