Diagnosis Of Neuromuscular Diseases Research Articles

Optimizing diagnosis of neuromuscular diseases by high-throughput sequencing: Genetic characterization and classification of sequence variants

Optimizing diagnosis of neuromuscular diseases by high-throughput sequencing: Genetic characterization and classification of sequence variants

Diagnostic neuromuscular ultrasound to confirm clinical significance of a genetic variant for Charcot-Marie-Tooth type 4C: A case report.

Neuromuscular ultrasound (NMUS) has emerged as a beneficial, complementary tool to EMG in the diagnosis of neuromuscular diseases as it provides high-resolution anatomic imaging of peripheral nerves and muscles. It has been used previously as an adjunct to EMG to diagnose Charcot-Marie-Tooth disease (CMT). Here, we present a case of a 64-year-old male with bilateral sensorineural hearing loss of 14 years who presented to an outpatient neuromuscular clinic at a tertiary medical center with very slow progressive paresthesias. This case highlights the application of NMUS to help confirm the presence of a likely CMT type 4C despite indeterminate genetic testing results and challenging EMG results. He had genetic testing which revealed a normal PMP22 gene; however, he had a variant of uncertain significance (VUS) in the SH3TC2 gene which has shown associations with autosomal recessive CMT4C. NMUS revealed mild median and significant tibial nerve uniform enlargement throughout their course. There may also be utility in performing NMUS on similarly affected family members if the same VUS returns for SH3TC2, with consideration of both peripheral nerve and nerve root assessment.

КЛИНИЧЕСКИЙ СЛУЧАЙ БОЛЕЗНИ КУГЕЛЬБЕРГА-ВЕЛАНДЕРА (СПИНАЛЬНОЙ МЫШЕЧНОЙ АТРОФИИ III ТИПА)

Background. Differential diagnosis of neuromuscular diseases is one of the most difficult areas in neurology. Molecular genetic research in these patients is of particular importance. The article presents a clinical case of 5q spinal muscular atrophy type III (Kugelberg – Welander disease), confirmed by molecular genetic testing. Description of the clinical case. The article presents the clinical observation of a patient with an initial diagnosis of Erb – Roth myopathy. A genetic study was carried out. The analysis of the presence of exon 7 of the SMN1/SMN2 genes showed the absence of a signal corresponding to exon 7 of the SMN1 gene. A search for deletions in the SMN1 gene showed the homozygous deletion of exons 7–8 of the SMN1 gene in the proband. Homozygous deletion of exons 7–8 of the SMN1 gene causes 5q proximal spinal muscular atrophy. As a result of determining the num-ber of copies of the SMN1 and SMN2 genes, 0 copies of exons 7–8 of the SMN1 gene and 4 copies of exons 7–8 of the SMN2 gene were registered, which confirms the diagnosis of 5q spinal muscular atrophy type III. Conclusion. Adult patients suffering from neuromuscular diseases are recommended to undergo confirmatory DNA diagnostics to prescribe pathogenetic treatment, which increases their chances of survival. In young people with a clinical diagnosis of neuromuscular disease, genetic testing is required to clarify the diagnosis and further treatment tactics.

Importance of accurate diagnosis of neuromuscular diseases for the sake of 6P medicine: Clinical case Kugelberg-Welander disease (spinal muscular atrophy type III)

Importance of accurate diagnosis of neuromuscular diseases for the sake of 6P medicine: Clinical case Kugelberg-Welander disease (spinal muscular atrophy type III)

Discrete wavelet transform based processing of embroidered textile-electrode electromyography signal acquired with load and pressure effect

The diagnosis of neuromuscular diseases is complicated by overlapping symptoms from other conditions. Textile-based surface electromyography (sEMG) of skeletal muscles, offer promising potential in diagnosis, treatment, and rehabilitation of various neuromuscular disorders. However, it is important to consider the impact of load and pressure on EMG signals, as this can significantly affect the signal’s accuracy. This study seeks to investigate the influence of load and pressure on EMG signals and establish a processing framework for these signals in the diagnosis of neuromuscular diseases. The sEMG data were collected from healthy subjects using a textile electrode developed from polyester multi-filament conductive hybrid thread (CleverTex). The textrode was embroidered directly on an elastic bandage (Velcro® strap) placed on volunteer’s muscles while different activities were performed with varying loads and pressure. The collected data were pre-processed using standard techniques of the discrete wavelet transform to remove noise and artifacts. The performance of the proposed denoising algorithm was evaluated using the signal-to-noise ratio (SNR), percentage root mean square difference (PRD), and root mean square error (RMSE). Various signal processing approaches (filters) were considered and the results were compared with the proposed EMG noise reduction algorithms. Based on the experimental results, the fourth level of decomposition for the sym5 wavelets with the Rigrsure threshold method achieved the highest signal-to-noise ratio (SNR) values of 16.69 and 21.91, for soft and hard thresholding functions, respectively. The SNR values of 22.11, 21.54, and 2.78 at three different pressure levels 5 mmHg, 10 mmHg, and 20 mmHg, respectively, indicate the superior performance of wavelet multiresolution filter in de-noising applications. The results of this study suggest that our methodology is effective, precise, and reliable for analysing sEMG data and provide insights into both physiological and pathological neuromuscular conditions.

Artificial Intelligence Applications in the Diagnosis of Neuromuscular Diseases: A Narrative Review.

The accurate diagnosis of neuromuscular diseases (NMD) is in many cases difficult; the starting point is the clinical approach based on the course of the disease and a careful physical examination of the patient. Electrodiagnostic tests, imaging, muscle biopsy, and genetics are fundamental complementary studies for the diagnosis of NMD. The large volume of data obtained from such studies makes it necessary to look for efficient solutions, such as artificial intelligence (AI) applications, which can help classify, synthesize, and organize the information of patients with NMD to facilitate their accurate and timely diagnosis. The objective of this study was to describe the usefulness of AI applications in the diagnosis of patients with neuromuscular diseases. A narrative review was done, including publications on artificial intelligence applied to the diagnostic methods of NMD currently existing. Twelve studies were included. Two of the studies focused on muscle ultrasound, five of the studies on muscle MRI, two studies on electromyography, two studies on amyotrophic lateral sclerosis (ALS) biomarkers, and one study on genes related to myopathies. The accuracy of classification using different classification algorithms used in each of the studies included in this narrativereview was already 90% in most studies. In conclusion,the future design of more accurate algorithms applied to NMD with greater precision will have an impact on the earlier diagnosis of this group of diseases.

Effect of the COVID-19 pandemic on outpatient care and rehabilitation in neuromuscular clinical practice in Japan: a health insurance claims database analysis

ObjectivesTo evaluate the impact of the COVID-19 pandemic on outpatient care in Japanese patients with neuromuscular diseases (NMDs).DesignThis retrospective cohort study included patients between January 2018 and February 2019; the...

Reducing Noise, Artifacts and Interference in Single-Channel EMG Signals: A Review

Electromyography (EMG) is gaining importance in many research and clinical applications, including muscle fatigue detection, control of robotic mechanisms and prostheses, clinical diagnosis of neuromuscular diseases and quantification of force. However, EMG signals can be contaminated by various types of noise, interference and artifacts, leading to potential data misinterpretation. Even assuming best practices, the acquired signal may still contain contaminants. The aim of this paper is to review methods employed to reduce the contamination of single channel EMG signals. Specifically, we focus on methods which enable a full reconstruction of the EMG signal without loss of information. This includes subtraction methods used in the time domain, denoising methods performed after the signal decomposition and hybrid approaches that combine multiple methods. Finally, this paper provides a discussion on the suitability of the individual methods based on the type of contaminant(s) present in the signal and the specific requirements of the application.

A clustering-based method for estimating pennation angle from B-mode ultrasound images.

B-mode ultrasound (US) is often used to noninvasively measure skeletal muscle architecture, which contains human intent information. Extracted features from B-mode images can help improve closed-loop human-robotic interaction control when using rehabilitation/assistive devices. The traditional manual approach to inferring the muscle structural features from US images is laborious, time-consuming, and subjective among different investigators. This paper proposes a clustering-based detection method that can mimic a well-trained human expert in identifying fascicle and aponeurosis and, therefore, compute the pennation angle. The clustering-based architecture assumes that muscle fibers have tubular characteristics. It is robust for low-frequency image streams. We compared the proposed algorithm to two mature benchmark techniques: UltraTrack and ImageJ. The performance of the proposed approach showed higher accuracy in our dataset (frame frequency is 20Hz), that is, similar to the human expert. The proposed method shows promising potential in automatic muscle fascicle orientation detection to facilitate implementations in biomechanics modeling, rehabilitation robot control design, and neuromuscular disease diagnosis with low-frequency data stream.

Normal Nerve Conduction Values of Median and Ulnar Nerves in the Turkish Population

ABSTRACT Background: Nerve conduction studies (NCS) are an important tool for the diagnosis of neuromuscular diseases. In NCS, factors such as temperature, age, sex, body metrics, and recording technique can affect the values. There are currently no universal normative data. The standardization of NCS is essential for the reliable and consistent identification of pathologic conditions for each laboratory. Aim: We wanted to obtain normal values of our electrophysiology laboratory for the Turkish population. Materials and Methods: The volunteer group consisted of 120 people aged 15–74 years. They were distributed into 12 subgroups according to their age. Each subgroup included five male and five female subjects. Age, sex, weight, height, profession, body mass index, and hand preferences were recorded. Median and ulnar NCS were performed by two experienced clinical neurophysiologists. The skin temperature was corrected to 35.5°C, which was the highest measured value. Results: Age 50 years was used for the cutoff point for nerve conduction velocities (NCVs) because there was no significant difference within the groups aged ≥50 years and <50 years. However, the NCVs of groups aged <50 years and >50 years were significantly different. NCVs and action potential amplitudes were higher in females than males in both age groups. Women had higher NCV values and action potential amplitudes of motor and sensory fibers. Conclusion: Age, temperature, and sex are important factors that affect NCS. We believe this study will provide normal values for future studies, especially in the Turkish population.

Ambulatory transcutaneous carbon dioxide monitoring for children with neuromuscular disease

ObjectiveEarly screening and diagnosis of nocturnal hypoventilation can slow progression to diurnal hypercapnia and mortality in children with neuromuscular disease (NMD). However, gold standard, laboratory-based polysomnography (PSG) testing is a limited resource. Therefore, we evaluated the diagnostic accuracy of ambulatory transcutaneous carbon dioxide (tcCO2) monitoring used in the home compared to PSG in children with NMD. MethodsProspective, cross-sectional study in children 0–18 years old with a confirmed diagnosis of NMD and a clinically indicated need for PSG. Ambulatory tcCO2 was assessed by a respiratory therapist in participant's homes. Demographics, and PSG (including tcCO2). ResultsWe enrolled 39 children with NMD; 3 had unusable ambulatory tcCO2 data because of failure of drift correction on the machine (n = 2) or an air bubble (n = 1). The remaining 36 patients aged 11 months to 16 years (median (IQR) 12.5 years (6.0–15.8)) had ambulatory tcCO2 and outpatient level 1 PSG data. Ambulatory tcCO2 monitoring had a sensitivity of 20.0% (95% confidence interval [CI] 0.5–71.6%) and a specificity of 93.5% (95% CI 78.6–99.2%). Almost all children and/or parents (34/36, 94%) preferred ambulatory monitoring over in-hospital PSG. ConclusionsAmbulatory transcutaneous carbon dioxide monitoring was not sufficiently accurate as a clinical tool for the diagnosis of nocturnal hypoventilation our cohort of children with neuromuscular disease despite being preferred over PSG by both children and parents.

FP.08 Evaluating the expression of spontaneous movements in infants with neuromuscular conditions using Prechtl's General Movements Assessment

Prechtl's General Movements Assessment (GMA) was originally developed to assist in early identification of infants with cerebral palsy by using gestalt visual analysis to evaluate infants' spontaneous movements. Little is understood about the types of general movements (GMs) expressed in infants with neuromuscular disorders, or whether these infants have detectable movement abnormalities within the first weeks of life. We seek to describe the expression of GMs in infants from birth to 6 months of age with diagnosis of neuromuscular disease. Fourteen infants with an established neuromuscular diagnosis (e.g., spinal muscular atrophy [SMA], N=7; Duchenne muscular dystrophy [DMD], N=3; and others, N=4) have been enrolled, to date. The GMs of each infant were recorded for up to 4 minutes in supine using standardized procedures. Blinded assessors used global GMA categorizations and detailed GMA scoring forms to evaluate the variability and complexity of the infants' movements and determine normal vs aberrant movement patterns. Two subjects (SMA, N=1; DMD, N=1) have >1 recording over time. Of the 17 total videos collected, 14 were able to be scored by the GMA. Four (29%) were evaluated as having normal movement patterns; of those, 2 were post-treatment SMA. A sub-cohort of infants were evaluated with the Neuromuscular Gross Motor Outcome (GRO) and Bayley-4 gross motor subtest as clinical standard of care. Interestingly, there was a moderate correlation between motor performance on GRO and GMA detailed scoring (rho=0.79; p=0.01), however, Bayley-4 scaled scores do not seem to differentiate between healthy and aberrant movements. Further exploration into the influence of disease-modifying treatments on the expression of GMs will be presented. While a limitation of this analysis was the small sample size, preliminary results suggest that many infants with neuromuscular disease express movement abnormalities from birth.

SEROPOSITIVE MYASTHENIA GRAVIS AS THE CAUSE OF MULTIPLE FAILED EXTUBATIONS AND A PROLONGED ICU STAY FOR COVID-19 PNEUMONIA: A CASE REPORT AND BRIEF LITERATURE REVIEW

SEROPOSITIVE MYASTHENIA GRAVIS AS THE CAUSE OF MULTIPLE FAILED EXTUBATIONS AND A PROLONGED ICU STAY FOR COVID-19 PNEUMONIA: A CASE REPORT AND BRIEF LITERATURE REVIEW

EMPATIA: A Guide for Communicating the Diagnosis of Neuromuscular Diseases.

Introduction: Neuromuscular diseases comprise a heterogeneous group of genetic syndromes that lead to progressive muscle weakness, resulting in functional limitation. There is a gap in the literature regarding the communication of the diagnosis of such diseases, compromising the autonomy of patients and families, besides causing stress on the assistant physician. Objectives: Developing a guide to reduce communication barriers in the diagnosis of neuromuscular diseases. Methodology: Systematic review, after searching the descriptors (“Muscular Diseases” OR “Neuromuscular Diseases”) AND (“Truth Disclosure” OR “Bad news communication” OR “Breaking bad News”) in the Pubmed, Bireme, and Scopus websites, and these results were analyzed through narrative textual synthesis. Results: 16 articles were submitted to the final analysis, giving rise to seven steps to support the communication process. These are Empathy, Message, Prognosis, Reception, Time, Individualization, and Autonomy. Discussion and conclusion: The empathic transmission of the message and the prognosis must accommodate the feelings of the interlocutors with different information needs. In this way, communication planning optimizes the time and individualizes each context, respecting the autonomy of those involved. EMPATIA reflects the bioethical and interdisciplinary analysis of the literature and comes to fill the gap related to the communication of bad news in neuromuscular diseases.

Muscle Fatigue Analysis by Visualization of Dynamic Surface EMG Signals Using Markov Transition Field.

Muscle fatigue analysis is important in the diagnosis of neuromuscular diseases. Analysis of surface electromyography (sEMG) signals by non-linear probabilistic approach is useful in studying their transitions and thus the neuromuscular system. In this study, a method to visualize sEMG signals using Markov transition field (MTF) under fatigue conditions is proposed. sEMG signals are acquired from 45 healthy participants during biceps curl exercise. They are filtered and divided into ten equal segments. Markov transition matrix is constructed and corresponding MTF image is generated. The average self-transition probability is extracted and compared for both non-fatigue and fatigue segments. It is observed that the extracted feature shows high statistical significance with p value less than 0.001. The increase in average self-transition probability under fatigue condition correlates with the reduction in the degree of signal complexity. Thus, encoding of sEMG signals to images is helpful in analyzing the complexity of the neuromuscular system. Clinical Relevance- This approach may be helpful in analyzing muscle fatigue related with various myoneural conditions.

Neuromuscular diseases in the pediatric intensive care unit: 11 years of experience from a tertiary children’s hospital

Background & Objective: We present 11-year data of patients with neuromuscular disease (NMD) that were treated in the pediatric intensive care unit of a tertiary children’s hospital. Methods: The data of all cases followed-up in the pediatric intensive care unit (PICU) were retrospectively analyzed. Patients were evaluated in terms of age, gender, diagnosis, PRISM, neuroanatomical localization, hospitalization time-age, cause of admission to pediatric intensive care unit, clinical course, complications and clinical discharge status. Results: A NMD was detected in 43 of the 1,411 patients admitted within the study period and accounted for approximately 3% of pediatric intensive care unit admissions. NMD consisted of genetic (n= 35, 74.8%), acquired (n=6, 13.8%) and metabolic (n=2, 4.6%) causes. The diagnoses included spinal muscular atrophy type 1 (n=12, 27.9%), Duchenne and Becker muscular dystrophy (n=7, 16.2%), congenital myopathy (n=6, 13.9%), congenital muscular dystrophy (n=5, 11.6%), Guillain-Barre syndrome and its variants (n=2, 4.6%), spinal muscular atrophy associated with respiratory distress type 1 (n=2, 2.3%), critical illness neuropathy (n=2, 4.6%), acute flaccid myelitis (n=2, 4.6%), congenital myasthenic syndrome (n=1, 2.3%), peripheral neuropathy associated with disorder of riboflavin transporter (n=1, 2.3%), juvenile amyotrophic lateral sclerosis (n=1, 2.3%), stress-induced childhood-onset neurodegeneration with ataxia and variable seizures (n=1, 2.3%), and metabolic myopathy (n=1, 2.3%). Respiratory complications (n=31, 72%) were the most common reasons of admission to the pediatric intensive care unit. Seven (16.2%) patients have the NMD diagnosis confirmed during their first admission in PICU. These included both genetic cause of NMDs (n=4) and acquired NMDs (n=3). Mortality rate was 6.9% (n=3). Forty-three patients diagnosed with NMD had 75 times PICU admissions. The disease with the highest rate of re-admission to the PICU was SMA type 1, and the most common reason for re-admission was respiratory reasons. Conclusion: Accurate diagnosis of NMD and knowledge of causes of admission to PICU is crucial for increasing awareness, sensitivity and effectiveness when treating these diseases.

68-year old man with progressive weakness and ventilator dependent respiratory failure: a case report of sporadic late onset nemaline myopathy

BackgroundNeuromuscular pathologies must be considered when caring for patients with persistent or progressive respiratory failure. Pertinent disease states may involve skeletal muscles of respiration or associated neurologic structures including motor neurons, peripheral neurons and the neuromuscular junction. Diagnosis may require pulmonary function testing, neurophysiologic studies, imaging, and/or muscle biopsy.Case presentationA 68-year-old male was transferred to our intensive care unit (ICU) for management of ventilator dependent respiratory failure. Upon further historical review, he described gradually worsening gait instability and muscle weakness, which was previously attributed to vascular Parkinsonism in the setting of known cerebrovascular disease. Upon arrival to our hospital, he was found to have elevated muscle specific enzymes, prompting evaluation for neuromuscular causes of respiratory failure. He was also found to have elevated HMG-CoA Reductase (HMGCR) antibodies. Ultimately, a right quadriceps muscle biopsy was performed and electron microscopy identified nemaline bodies within skeletal myofibers. Given the clinical course and other histopathologic findings, he was diagnosed with Sporadic late-onset nemaline myopathy (SLONM).ConclusionThe diagnosis of neuromuscular disease in patients with ventilator dependent respiratory failure is challenging. A detailed history of a patient’s clinical course prior to hospitalization is key and may raise suspicion for underlying neuromuscular pathology. Further evaluation in non-critically ill patients may include pulmonary function, electromyography and confirmatory muscle biopsy. Sporadic late onset nemaline myopathy remains a rare disease entity which rarely presents with respiratory failure and lacks effective treatment.

Neuromuscular Patients Are 40% More Likely to Get a Cast Injury.

Cast injuries can occur during application, throughout immobilization, and during removal, with common morbidities being pressure ulcers and cast saw burns. The incidence rate of cast injuries in generalized and diagnosis specific pediatric populations is not known. The goal of this study is to accurately quantify the rate of incidence of cast injuries at a large pediatric orthopaedic practice and identify potentially modifiable risk factors to guide quality of care improvement. A retrospective review was performed at our institution between July 2019 and October 2020. Inclusion criteria was all pediatric patients (below 21 y old) with an orthopaedic diagnosis that was treated with casting. The child's diagnosis, specific type of cast, and training level of the person applying the cast was recorded. Patient injuries were identified through cast technicians' documentation regarding cast removal. The primary outcome was the incidence of casting injuries from July 2019 through October 2020. Additional outcomes included the association between diagnosis of neuromuscular disease and training level of individual applying the cast with casting injuries. χ2 tests were used to compare categorical variables and post hoc comparisons using Bonferroni correction. Injury incidence rates were calculated as number of injuries per 1000 casts. There were 2239 casts placed on children at this institution between July 2019 and October 2020 and a total of 28 injuries for an incidence rate of 12.5 per 1000. Of the 28 total injuries reported, there were 5 cast saw burns (2.2 per 1000) and 23 pressure ulcers (10.3 per 1000). Incidence of cast injury was not significantly correlated with timing of application during the academic year or training level of the individual applying the cast (P=0.21 and 0.86). Notably, there was a significantly higher incidence of cast injuries in individuals with a diagnosis of a neuromuscular disorder (37.4 per 1000) than those without (7.5 per 1000) (P<0.01). The incidence of cast injuries is 12.5 per 1000 children at our level I trauma tertiary referral pediatric clinic. Training level of the individual applying the cast or timing during the academic year did not correlate with cast injuries. Patients with neuromuscular disorders are at significantly higher risk for experiencing cast injuries. Level III.

Prevalence and incidence of neuromuscular conditions in the UK between 2000 and 2019: A retrospective study using primary care data.

In the UK, large-scale electronic primary care datasets can provide up-to-date, accurate epidemiological information on rarer diseases, where specialist diagnoses from hospital discharges and clinic letters are generally well recorded and electronically searchable. Current estimates of the number of people living with neuromuscular disease (NMD) have largely been based on secondary care data sources and lacked direct denominators. To estimate trends in the recording of neuromuscular disease in UK primary care between 2000-2019. The Clinical Practice Research Datalink (CPRD) database was searched electronically to estimate incidence and prevalence rates (per 100,000) for a range of NMDs in each year. To compare trends over time, rates were age standardised to the most recent CPRD population (2019). Approximately 13 million patients were actively registered in each year. By 2019, 28,230 active patients had ever received a NMD diagnosis (223.6), which was higher among males (239.0) than females (208.3). The most common classifications were Guillain-Barre syndrome (40.1), myasthenia gravis (33.7), muscular dystrophy (29.5), Charcot-Marie-Tooth (29.5) and inflammatory myopathies (25.0). Since 2000, overall prevalence grew by 63%, with the largest increases seen at older ages (≥65-years). However, overall incidence remained constant, though myasthenia gravis incidence has risen steadily since 2008, while new cases of muscular dystrophy fell over the same period. Lifetime recording of many NMDs on primary care records exceed current estimates of people living with these conditions; these are important data for health service and care planning. Temporal trends suggest this number is steadily increasing, and while this may partially be due to better recording, it cannot be simply explained by new cases, as incidence remained constant. The increase in prevalence among older ages suggests increases in life expectancy among those living with NMDs may have occurred.

Ultrasound Imaging of the Diaphragm

The diaphragm is the major muscle of respiration and its dysfunction is associated with problems ranging from orthopnea to prolonged recovery from surgery or ventilator management. Common causes of diaphragm dysfunction include phrenic neuropathy, motor neuron disease, neuromuscular junction disorders, and myopathy. This article reviews sonographic findings of normal diaphragm, including key quantitative ultrasound measurements that are helpful in the evaluation of diaphragm. It also discusses various clinical application of this technique in diagnosis of neuromuscular diseases.