Cervical root sonography to differentiate multifocal motor neuropathy from ALS

To explore suggestive evidence of focal proximal demyelination in multifocal motor neuropathy (MMN) without overt evidence of conduction block, we conducted sonographical assessment of cervical nerve roots in 9 MMN patients, 22 ALS patients, and 17 control subjects. The mean diameters of the C5 and C6 roots in MMN patients were significantly larger than those in ALS and controls, especially on the clinically dominant side. Although non-specific, sonography can be a potentially useful diagnostic procedure to support the diagnosis of MMN, even when overt conduction block is lacking

Utility of phrenic nerve ultrasound in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting the upper and lower motor neurons causing progressive weakness. It eventually involves the diaphragm which leads to respiratory paralysis and subsequently death. Phrenic nerve (PN) conduction studies and diaphragm ultrasound has been studied and correlated with pulmonary function tests in ALS patients. However, PN ultrasonography has not been employed in ALS. This study aims to sonographically evaluate the morphologic appearance of the PN of ALS patients. Thirty-eight ALS patients and 28 normal controls referred to the neurophysiology laboratory of two institutions were retrospectively included in the study. Baseline demographic and clinical variables such as disease duration, ALS Functional Rating Scale-Revised score, and ALS region of onset were collected. Ultrasound was used to evaluate the PN cross-sectional area (CSA) of ALS and control subjects. The mean PN CSA of ALS patients were 1.08 ± 0.39 mm on the right and 1.02 ± 0.34 mm on the left. The PN CSA of ALS patients were significantly decreased compared to controls (p value < 0.00001). The PN CSA of ALS patients was not correlated to any of the demographic and clinical parameters tested. This study demonstrates that ALS patients have a smaller PN size compared to controls using ultrasonography

Texture analysis of myopathy

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

Texture in aging

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

Sonographic evaluation of cervical nerve roots in ALS and its clinical subtypes

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

Which muscle shows fasciculations by ultrasound in patients with ALS?

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

Distinct Incidence of Takotsubo Syndrome Between Amyotrophic Lateral Sclerosis and Synucleinopathies: A Cohort Study

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

TTS in ALS and Synucleinopathies

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

Natural Attenuation of Mn(II) in Metal Refinery Wastewater: Microbial Community Structure Analysis and Isolation of a New Mn(II)-Oxidizing Bacterium Pseudomonas sp. SK3

Natural attenuation of Mn(II) was observed inside the metal refinery wastewater pipeline, accompanying dark brown-colored mineralization (mostly MnIVO2 with some MnIII2O3 and Fe2O3) on the inner pipe surface. The Mn-deposit hosted the bacterial community comprised of Hyphomicrobium sp. (22.1%), Magnetospirillum sp. (3.2%), Geobacter sp. (0.3%), Bacillus sp. (0.18%), Pseudomonas sp. (0.03%), and non-metal-metabolizing bacteria (74.2%). Culture enrichment of the Mn-deposit led to the isolation of a new heterotrophic Mn(II)-oxidizer Pseudomonas sp. SK3, with its closest relative Ps. resinovorans (with 98.4% 16S rRNA gene sequence identity), which was previously unknown as an Mn(II)-oxidizer. Oxidation of up to 100 mg/L Mn(II) was readily initiated and completed by isolate SK3, even in the presence of high contents of MgSO4 (a typical solute in metal refinery wastewaters). Additional Cu(II) facilitated Mn(II) oxidation by isolate SK3 (implying the involvement of multicopper oxidase enzyme), allowing a 2-fold greater Mn removal rate, compared to the well-studied Mn(II)-oxidizer Ps. putida MnB1. Poorly crystalline biogenic birnessite was formed by isolate SK3 via one-electron transfer oxidation, gradually raising the Mn AOS (average oxidation state) to 3.80 in 72 h. Together with its efficient in vitro Mn(II) oxidation behavior, a high Mn AOS level of 3.75 was observed with the pipeline Mn-deposit sample collected in situ. The overall results, including the microbial community structure analysis of the pipeline sample, suggest that the natural Mn(II) attenuation phenomenon was characterized by robust in situ activity of Mn(II) oxidizers (including strain SK3) for continuous generation of Mn(IV). This likely synergistically facilitated chemical Mn(II)/Mn(IV) synproportionation for effective Mn removal in the complex ecosystem established in this artificial pipeline structure. The potential utility of isolate SK3 is illustrated for further industrial application in metal refinery wastewater treatment processes