A Case of Anti-NXP2 Antibody-positive Juvenile Dermatomyositis with Characteristic Fascial Thickening on Muscle Ultrasound and Improvement with Immunotherapy.

We herein report a 12-year-old boy who presented with a fever, erythematous rash on the cheeks, back pain, and dysphagia. Blood tests revealed increased creatine kinase levels, and muscle ultrasonography (MUS) revealed characteristic fascial thickening in the lumbar paraspinal muscles, where myalgia was prominent. Sarcoplasmic expression of myxovirus-resistant protein A on a muscle biopsy and the presence of anti-nuclear matrix protein 2 (NXP2) antibodies confirmed the diagnosis of dermatomyositis. Prednisolone and intravenous immunoglobulin therapy improved the clinical and laboratory parameters as well as fascial thickening. MUS is useful for evaluating fasciitis associated with anti-NXP2 autoantibodies and monitoring therapeutic efficacy.

Correlation of muscle ultrasound with clinical and pathological findings in idiopathic inflammatory myopathies.

INTRODUCTION/AIMS: In idiopathic inflammatory myopathies (IIMs), the change in muscle echogenicity and its histopathological basis are not well understood. We quantitatively measured muscle echogenicity in patients with IIMs and evaluated its correlation with disease activity and histopathological findings. METHODS: This study involved patients with IIMs who underwent both ultrasonography (US) and muscle biopsy, as well as age- and sex-matched rheumatoid arthritis patients as inflammatory disease controls. On US, axial images of the right biceps brachii and vastus medialis were obtained. Standardized histopathological scoring was used to quantitatively measure each pathological domain. RESULTS: Forty-two patients (17 with inclusion body myositis [IBM] and 25 with IIMs other than IBM) and 25 controls were included. The muscle echo intensity (EI) of patients with IIMs was significantly higher than that of controls. Muscle EI showed significant correlations with creatine kinase (r = 0.66, p < .001) and muscle strength (r = -0.73, p < .0001) in patients with non-IBM IIMs. In patients with IBM, moderate correlation was found between muscle EI and quadriceps muscle strength (r = -0.53, p = .028). Histopathologically, the number of infiltrating CD3+ inflammatory cells correlated with muscle EI in the non-IBM group (r = 0.56, p = .017), but not in the IBM group. DISCUSSION: Muscle EI may be useful as a surrogate marker of muscle inflammation in non-IBM IIM. Increased muscle EI may be difficult to interpret in patients with long-standing IBM, which has advanced and complex histopathology.

Application of ultrasound in a case of eosinophilic fasciitis mimicking stiff-person syndrome.

Eosinophilic fasciitis (EF) is a rare disorder characterized by muscle stiffness mimicking other neuromuscular diseases. The diagnosis of EF is made on the basis of typical skin lesions. We report a case of a 36-year-old male patient with suspected stiff-person syndrome (SPS), who presented with progressive limb muscle stiffness and limited mobility of both wrists without obvious skin changes. Ultrasound revealed fascial thickening of bilateral upper and lower limb muscles and enlargement of hypoechoic tissues around the flexor digitorum tendons of the wrist. Skin and fascia biopsy confirmed the diagnosis of EF. Prednisolone therapy resulted in the improvement of muscle stiffness and tightness. Our findings suggest the need to consider connective tissue diseases such as EF in a patient with atypical features of SPS. Ultrasound is helpful for visualizing the causes of muscle stiffness and joint contractures in EF patients.

Early diagnosis of amyotrophic lateral sclerosis based on fasciculations in muscle ultrasonography: A machine learning approach.

OBJECTIVE: Although fasciculation on muscle ultrasonography (MUS) is useful in diagnosing amyotrophic lateral sclerosis (ALS), its applicability to early diagnosis remains unclear. We aimed to develop and validate diagnostic models especially beneficial to early-stage ALS via machine learning. METHODS: We investigated 100 patients with ALS, including 50 with early-stage ALS within 9 months from onset, and 100 without ALS. Fifteen muscles were bilaterally observed for 10 s each and the presence of fasciculations was recorded. Hierarchical clustering and nominal logistic regression, neural network, or ensemble learning were applied to the training cohort comprising the early-stage ALS to develop MUS-based diagnostic models, and they were tested in the validation cohort comprising the later-stage ALS. RESULTS: Fasciculations on MUS in the brainstem or thoracic region had high specificity but limited sensitivities and predictive profiles for diagnosis of ALS. A machine learning-based model comprising eight muscles in the four body regions had a high sensitivity (recall), specificity, and positive predictive value (precision) for both early- and later-stage ALS patients. CONCLUSIONS: We developed and validated MUS-fasciculation-based diagnostic models for early- and later-stage ALS. SIGNIFICANCE: Fasciculation detected in relevant muscles on MUS can contribute to the diagnosis of ALS from the early stage.

Nerve ultrasound characteristics of immunoglobulin M neuropathy associated with anti-myelin-associated glycoprotein antibodies.

INTRODUCTION/AIMS: Immunoglobulin M neuropathy associated with anti-myelin-associated glycoprotein antibody (IgM/anti-MAG) neuropathy typically presents with chronic, distal-dominant symmetrical sensory or sensorimotor deficits. Ultrasonographic studies of IgM/anti-MAG neuropathy are limited, and were all performed on Western populations. We aimed to characterize the nerve ultrasonographic features of IgM/anti-MAG neuropathy in the Japanese population and evaluate whether they differ from the findings of the common subtypes of chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: In this cross-sectional study, we retrospectively reviewed medical records and extracted the cross-sectional areas (CSAs) of C5-C7 cervical nerve roots and median and ulnar nerves of 6 IgM/anti-MAG neuropathy patients, 10 typical CIDP (t-CIDP) patients, 5 multifocal CIDP (m-CIDP) patients, and 17 healthy controls (HCs). RESULTS: Cervical nerve root CSAs were significantly larger at every examined site on both sides in IgM/anti-MAG neuropathy than in m-CIDP and HCs but were comparable to those in t-CIDP. Peripheral nerve enlargements were greatest at common entrapment sites (ie, wrist and elbow) in IgM/anti-MAG neuropathy, a pattern shared with t-CIDP but not with m-CIDP. The degree of nerve enlargement at entrapment sites compared to non-entrapment sites was significantly higher in IgM/anti-MAG neuropathy than in t-CIDP. DISCUSSION: Our study delineated the ultrasonographic features of IgM/anti-MAG neuropathy in the Japanese population and observed similar characteristics to those of t-CIDP, with subtle differences. Further studies comparing results from various populations are required to optimize the use of nerve ultrasound worldwide.

Cervical Root Enlargement in Segmental Zoster Paresis: A Study with Magnetic Resonance Imaging and Nerve Ultrasound.

A 72-year-old woman presented with acute-progressive muscle weakness after a rash in the left upper limb. Muscle weakness was restricted to the left C5 innervated muscles. Short inversion time inversion recovery magnetic resonance imaging (MRI) showed a high-intensity signal in the left C5 nerve root, and nerve ultrasound showed its enlargement. She was diagnosed with segmental zoster paralysis (SZP) and treated with acyclovir and methylprednisolone. Her muscle strength gradually recovered, and the abnormal signal and enlargement in the left C5 nerve root improved. This is the first SZP case of confirmed improvement of abnormal findings on MRI and nerve ultrasound in association with muscle power recovery.

Ultrasound assessment of sarcopenia in patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the efficacy of ultrasound (US) as a diagnostic tool for sarcopenia in patients with rheumatoid arthritis (RA). METHODS: Female RA patients aged >50 years and matched controls were cross-sectionally assessed. Sarcopenia was diagnosed based on the 2019-updated Asian Working Group for Sarcopenia definition. The cross-sectional area (CSA) and echo intensity (EI) of the biceps brachii, rectus femoris, and EI of the vastus lateralis were examined bilaterally. Correction for subcutaneous fat and calculation of the recorrected EI (rcEI) were performed. We performed logistic regression using both muscle rcEI and CSA with receiver operating curve analysis to evaluate the discriminative performance per muscle group. RESULTS: Seventy-eight consecutive RA patients and 15 age-and sex-matched controls were assessed. Sarcopenia was diagnosed in 34 RA patients (43.6%). The rcEI of examined muscles were significantly higher, whereas CSA were significantly lower in sarcopenic RA patients than in non-sarcopenic patients and matched controls. The combined discriminative performance of rcEI and CSA was superior to those of rcEI or CSA alone. CONCLUSIONS: This study suggests the use of US for the diagnosis of sarcopenia in RA patients. The diagnostic performance increases when both echogenicity and CSA are considered together rather than individually.

Sonographic Multifocal Cranial Nerve Enlargement in Multifocal Acquired Demyelinating Sensory and Motor Neuropathy.

Multifocal enlargements with the alteration of a normal fascicular pattern are considered to be sonographic peripheral nerve features in multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), a subtype of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We herein present the case of an 18-year-old patient with MADSAM in whom intensive sonological assessments revealed multifocal nerve enlargement within clinically affected cranial nerves. Our case demonstrated that, if systematically investigated with ultrasound, morphological changes similar to those in the peripheral nerves may be detected in a large proportion of clinically affected cranial nerves in MADSAM, boosting the future applications of cranial nerve ultrasound in CIDP.

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 sonographic muscle images can distinguish myopathic conditions.

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.

PMP22-related disease: A novel splice site acceptor variant and intrafamilial phenotype variability.

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.

Age-dependent texture features in skeletal muscle ultrasonography.

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.

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.

Neurogenic and Myogenic Diseases: Quantitative Texture Analysis of Muscle US Data for Differentiation.

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.

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.

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.