Electrical impedance myography (EIM) using surface techniques has shown promise as a means of diagnosing and tracking disorders affecting muscle and assessing treatment efficacy. However, the ...relationship between such surface-obtained impedance values and pure muscle impedance values has not been established. Here we studied three groups of diseased and wild-type (WT) animals, including a Duchenne muscular dystrophy model (the D2-mdx mouse), an amyotrophic lateral sclerosis (ALS) model (the SOD1 G93A mouse), and a model of fat-related atrophy (the db/db diabetic obese mouse), performing hind limb measurements using a standard surface array and ex vivo measurements on freshly excised gastrocnemius muscle. A total of 101 animals (23 D2-mdx, 43 ALS mice, 12 db/db mice, and corresponding 30 WT mice) were studied with EIM across a frequency range of 8 kHz to 1 MHz. For both D2-mdx and ALS models, moderate strength correlations (Spearman rho values generally ranging from 0.3-0.7, depending on the impedance parameter (i.e., resistance, reactance and phase) were obtained. In these groups of animals, there was an offset in frequency with impedance values obtained at higher surface frequencies correlating more strongly to impedance values obtained at lower ex vivo frequencies. For the db/db model, correlations were comparatively weaker and strongest at very high and very low frequencies. When combining impedance data from all three disease models together, moderate correlations persisted (with maximal Spearman rho values of 0.45). These data support that surface EIM data reflect ex vivo muscle tissue EIM values to a moderate degree across several different diseases, with the highest correlations occurring in the 10-200 kHz frequency range. Understanding these relationships will prove useful for future applications of the technique of EIM in the assessment of neuromuscular disorders.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background:
Dimethyl fumarate (DMF) depletes CD8+ and CD4+ T cells, and cases of herpes zoster (HZ) in patients with multiple sclerosis (MS) on DMF have been documented.
Objectives:
To evaluate ...lymphocyte subsets in patients with MS who developed HZ on DMF (Tecfidera) compared to matched controls who did not develop HZ.
Methods:
We used linear mixed-effects models to test for differences in white blood cell count, lymphocyte percentage, absolute lymphocyte count, CD3+ percentage, absolute CD3+ count, CD4+ percentage, absolute CD4+ count, CD8+ percentage, absolute CD8+ count, and CD4+:CD8+ ratio over time in HZ and non-HZ groups.
Results:
Eighteen patients developed HZ while on DMF. The linear mixed-effects model for CD4+:CD8+ ratio showed a significant difference between the HZ and non-HZ groups (p = 0.033). CD4+:CD8+ ratio decreased over time in the HZ group and increased over time in the non-HZ group.
Conclusion:
Patients with MS who develop HZ while on DMF have high CD4+:CD8+ ratios, suggesting an imbalance of CD4+ and CD8+ cells that may put a patient at risk for developing HZ while on DMF. This result emphasizes the need for lymphocyte subset monitoring (including CD4+:CD8+ ratios) on DMF, as well as vaccination prior to DMF initiation.
Introduction/Aims
We assessed the classification performance of machine learning (ML) using multifrequency electrical impedance myography (EIM) values to improve upon diagnostic outcomes as compared ...to those based on a single EIM value.
Methods
EIM data was obtained from unilateral excised gastrocnemius in eighty diseased mice (26 D2‐mdx, Duchenne muscular dystrophy model, 39 SOD1G93A ALS model, and 15 db/db, a model of obesity‐induced muscle atrophy) and 33 wild‐type (WT) animals. We assessed the classification performance of a ML random forest algorithm incorporating all the data (multifrequency resistance, reactance and phase values) comparing it to the 50 kHz phase value alone.
Results
ML outperformed the 50 kHz analysis as based on receiver‐operating characteristic curves and measurement of the area under the curve (AUC). For example, comparing all diseases together versus WT from the test set outputs, the AUC was 0.52 for 50 kHz phase, but was 0.94 for the ML model. Similarly, when comparing ALS versus WT, the AUCs were 0.79 for 50 kHz phase and 0.99 for ML.
Discussion
Multifrequency EIM using ML improves upon classification compared to that achieved with a single‐frequency value. ML approaches should be considered in all future basic and clinical diagnostic applications of EIM.
Background
Electrical impedance myography (EIM) provides insight into muscle composition and structure. We sought to evaluate its use in a mouse obesity model characterized by myofiber atrophy.
...Methods
We applied a prediction algorithm, ie, the least absolute shrinkage and selection operator (LASSO), to surface, needle array, and ex vivo EIM data from db/db and wild‐type mice and assessed myofiber cross‐sectional area (CSA) histologically and triglyceride (TG) content biochemically.
Results
EIM data from all three modalities provided acceptable predictions of myofiber CSA with average root mean square error (RMSE) of 15% in CSA (ie, ±209 μm2 for a mean CSA of 1439 μm2) and TG content with RMSE of 30% in TG content (ie, ±7.3 nmol TG/mg muscle for a mean TG content of 25.4 nmol TG/mg muscle).
Conclusions
EIM combined with a predictive algorithm provides reasonable estimates of myofiber CSA and TG content without the need for biopsy.
Introduction
Surface electrical impedance myography (sEIM) has the potential for providing information on muscle composition and structure noninvasively. We sought to evaluate its use to predict ...myofiber size and connective tissue deposition in the D2‐mdx model of Duchenne muscular dystrophy (DMD).
Methods
We applied a prediction algorithm, the least absolute shrinkage and selection operator, to select specific EIM measurements obtained with surface and ex vivo EIM data from D2‐mdx and wild‐type (WT) mice (analyzed together or separately). We assessed myofiber cross‐sectional area histologically and hydroxyproline (HP), a surrogate measure for connective tissue content, biochemically.
Results
Using WT and D2‐mdx impedance values together in the algorithm, sEIM gave average root‐mean‐square errors (RMSEs) of 26.6% for CSA and 45.8% for HP, which translate into mean errors of ±363 μm2 for a mean CSA of 1365 μm2 and of ±1.44 μg HP/mg muscle for a mean HP content of 3.15 μg HP/mg muscle. Stronger predictions were obtained by analyzing sEIM data from D2‐mdx animals alone (RMSEs of 15.3% for CSA and 34.1% for HP content). Predictions made using ex vivo EIM data from D2‐mdx animals alone were nearly equivalent to those obtained with sEIM data (RMSE of 16.59% for CSA), and slightly more accurate for HP (RMSE of 26.7%).
Discussion
Surface EIM combined with a predictive algorithm can provide estimates of muscle pathology comparable to values obtained using ex vivo EIM, and can be used as a surrogate measure of disease severity and progression and response to therapy.
Cognitive decline in Huntington's disease (HD) begins early in the disease course, however the reported prevalence and severity of cognitive impairment varies based on diagnostic approach. A Movement ...Disorders Society Task Force recently endorsed the use of standardized DSM-5-based criteria to diagnose neurocognitive disorder (NCD) in Huntington's disease.
To determine the prevalence and severity of cognitive impairment across different stages of HD by applying NCD criteria (mild and major) to participant data from the Enroll-HD database.
Enroll-HD participants were triaged into either premanifest (preHD), manifest or control groups. PreHD was further dichotomized into preHD near or preHD far based on predicted time to diagnosis using the scaled CAG-age product score (CAPs). Embedded cognitive performance and functional independence measures were used to determine prevalence of NCD (mild and major) for all groups.
Prevalence of NCD-mild was 25.2%-38.4% for manifest HD, 22.8%-47.3% for preHD near, 11.5%-25.1% for preHD far, and 8.8%-19.1% for controls. Prevalence of NCD-major was 21.1%-57.7% for manifest HD, 0.5%-16.3% for preHD near, 0.0%-4.5% for preHD far, and 0.0%-3.0% for controls.
The prevalence of NCD in HD is elevated in preHD and demonstrates a sharp rise prior to diagnosis. In manifest HD, the vast majority of participants meet criteria for NCD. These findings are important for optimizing clinical care and/or anticipating the need for supportive services.
Cognitive decline is an important early sign in pre-motor manifest Huntington's disease (preHD) and is characterized by deficits across multiple domains including executive function, psychomotor ...processing speed, and memory retrieval. Prior work suggested that the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L)-a verbal learning task that simultaneously targets these domains - could capture early cognitive changes in preHD. The current study aimed to replicate, validate and further analyze the LASSI-L in preHD using larger datasets.
LASSI-L was administered to 50 participants (25 preHD and 25 Healthy Controls) matched for age, education, and sex in a longitudinal study of disease progression and compared to performance on MMSE, Trail A & B, SCWT, SDMT, Semantic Fluency (Animals), and CVLT-II. Performance was then compared to a separate age-education matched-cohort of 25 preHD participants. Receiver operating curve (ROC) and practice effects (12 month interval) were investigated. Group comparisons were repeated using a preHD subgroup restricted to participants predicted to be far from diagnosis (Far subgroup), based on CAG-Age-Product scaled (CAPs) score. Construct validity was assessed through correlations with previously established measures of subcortical atrophy.
PreHD performance on all sections of the LASSI-L was significantly different from controls. The proactive semantic interference section (PSI) was sensitive (
= 0.0001,
= 1.548), similar across preHD datasets (
= 1.0), reliable on test-retest over 12 months (spearman rho = 0.88;
= <0.00001) and associated with an excellent area under ROC (AUROC) of 0.855. In the preHD Far subgroup comparison, PSI was the only cognitive assessment to survive FDR < 0.05 (
= 0.03). The number of intrusions on PSI was negatively correlated with caudate volume.
The LASSI-L is a sensitive, reliable, efficient tool for detecting cognitive decline in preHD. By using a unique verbal learning test paradigm that simultaneously targets executive function, processing speed and memory retrieval, the LASSI-L outperforms many other established tests and captures early signs of cognitive impairment. With further longitudinal validation, the LASSI-L could prove to be a useful biomarker for clinical research in preHD.
Convenient tools to assess canine skeletal muscle health would be useful for a variety of applications, including standard veterinary assessments of dog fitness, as well as studies of muscle ...deterioration due to age or disease. One technology that can be applied conveniently to awake dogs with minimal restraint is electrical impedance myography (EIM). In EIM, a weak electrical current is applied
surface electrodes to a muscle of interest and consequent impedance characteristics of the muscle are obtained, providing insight into muscle condition and composition. In this study, we assessed a total of 73 dogs (42 males and 31 females), of varied neutering status and breed, ages 0.6 to 13.5 years. We identified age-dependent reference values for the 100 kHz phase value in three pelvic limb muscles, caudal sartorius, cranial tibial, and gastrocnemius. While phase values were generally higher in males than females, the difference did not reach significance. In general, values declined on average with age at about 0.5 degrees/year, but with the decline being most substantial in the oldest dogs. Limited reproducibility assessment of the technique suggested good repeatability with variation in values between measurements being under 5%. These results show that EIM has the potential for the assessment of canine muscle health and may find value in aging muscle research.
Objective
To determine the potential for improving amyotrophic lateral sclerosis (ALS) clinical trials by having patients or caregivers perform frequent self‐assessments at home.
Methods and ...Participants
We enrolled ALS patients into a nonblinded, longitudinal 9‐month study in which patients and caregivers obtained daily data using several different instruments, including a slow‐vital capacity device, a hand grip dynamometer, an electrical impedance myography‐based fitness device, an activity tracker, a speech app, and the ALS functional rating scale‐revised. Questions as to acceptability were asked at two time points.
Results
A total of 113 individuals enrolled, with 61 (43 men, 18 women, mean age 60.1 ± 9.9 years) collecting a minimum of 7 days data and being included in the analysis. Daily measurements resulted in more accurate assessments of the slope of progression of the disease, resulting in smaller sample size estimates for a hypothetical clinical trial. For example, by performing daily slow‐vital capacity measurements, calculated sample size was reduced to 182 subjects/study arm from 882/arm for monthly measurements. Similarly, performing the ALS functional rating scale weekly rather than monthly led to a calculated sample size of 73/arm as compared to 274/arm. Participants generally found the procedures acceptable and, for many, improved their sense of control of their disease.
Interpretation
Frequent at‐home measurements using standard tools holds the prospect of tracking progression and reducing sample size requirements for clinical trials in ALS while also being acceptable to the patients. Future studies in this and other neurological disorders should consider adopting this approach to data collection.
Objective: Pulmonary function tests (PFTs) are important for assessing respiratory function in amyotrophic lateral sclerosis (ALS) patients. However, weakness of oral and glottal closure, due to ...concomitant bulbar dysfunction, may result in unreliable PFT values stemming from leakage of air around the breathing tube and through the glottis. In this study, we assessed whether standard thoracic electrical impedance tomography (EIT) could serve as a surrogate measure for PFTs. Approach: Thoracic EIT was performed simultaneously with standard PFTs on seven ALS patients without clinical bulbar weakness (six men and one woman, mean age of 63 years) and ten healthy volunteers (seven men and three women, mean age of 57 years). A raw impedance metric along with more standard EIT measures were computed and correlated with the normalized forced vital capacity (FVC). Additionally, test/re-test metrics and EIT images were analyzed. Main results: The impedance metric was found to be robust and sensitive to lung activity. We also identified qualitative EIT differences between healthy volunteers and ALS patients, with the ALS images showing greater heterogeneity. Significant correlations with FVC were found for both impedance and EIT metrics in ALS patients (r2 = 0.89) and for the impedance metric only in healthy volunteers (r2 = 0.49). Significance: This suggests that EIT, using our novel impedance metric, has the potential to serve as an alternative technology to standard PFTs for assessing pulmonary function in patients with ALS, offering new metrics of disease status for those with bulbar weakness.
PDF
