Johannes P. van Dijk

Quantitative muscle ultrasound is a promising longitudinal follow-up tool in Duchenne muscular dystrophy.

Responsive outcome measures are needed to follow the disease status of Duchenne muscular dystrophy (DMD) patients, as new therapeutic approaches become available for affected boys. Quantitative muscle ultrasound (QMUS) is potentially an attractive follow up tool for DMD because it reflects the severity of the dystrophic process without the need for invasive procedures, by quantifying echo intensity (i.e., mean grey level of muscle images) and muscle thickness. We performed a longitudinal follow-up of lower and upper extremity QMUS in 18 DMD patients and compared this with physical functioning in 11 of these patients. QMUS could be performed in every patient, and no patient was subjected to more than a total of 20min of ultrasound scanning time for this study. As expected we found a significant increase of echo intensity with age, reflecting increasing dystrophic muscle changes. This increase was related to ambulatory status, functional grading, muscle strength and motor ability. Our study establishes QMUS as a practical and child-friendly tool for the longitudinal follow up of DMD patients.

Motor Unit Number Index (MUNIX) : A novel neurophysiological marker for neuromuscular disorders; test-retest reliability in healthy volunteers

OBJECTIVE To investigate the intra-rater and inter-rater test-retest reliability of the Motor Unit Number Index (MUNIX) in healthy subjects in a multicentre setting. METHODS Six study centres applied the MUNIX technique in 66 healthy subjects. Five to six muscles (biceps brachii, BB; abductor digiti minimi, ADM; abductor pollicis brevis, APB; tibialis anterior, TA; extensor digitorum brevis, EDB and abductor hallucis, AH) were measured in each volunteer four times by two independent examiners. RESULTS The method was easy to perform and well tolerated. The intraclass correlation coefficient (ICC) varied between centres and muscles. Intra-rater reliability was greatest for the AH (ICC 0.83) and EDB (ICC 0.81). Inter-rater reliability was greatest for the AH (ICC 0.69) and ADM muscles (ICC 0.69). The most critical muscle was the APB muscle (ICC 0.52, total variability). This was mostly due to variability in the compound muscle action potential (CMAP) measurements. MUNIX values of the APB, ADM and TA fell into the same range as in other motor unit number estimation (MUNE) studies. CONCLUSION MUNIX measurements in multiple muscles show good inter- and intra-rater reliability in healthy subjects. CMAP amplitude must be controlled to optimize reliability. SIGNIFICANCE Results suggest that MUNIX could serve as a reliable marker for motor neuron loss in diseases like amyotrophic lateral sclerosis.

Quantitative gray-scale analysis in skeletal muscle ultrasound: a comparison study of two ultrasound devices.

Muscle ultrasound is a useful technique to detect neuromuscular disorders. Quantification of muscle echo intensity (EI) using gray‐scale analysis is more reliable and more sensitive compared with visual evaluation of the images. We devised a method to reliably use EI normal values established with one ultrasound device for use with another device. Based on measurements in a dedicated phantom and in 7 healthy subjects, a conversion equation was calculated to convert the mean EI. The reliability of this equation was next evaluated in a follow‐up study of 22 healthy children. Mean muscle EI could be reliably converted from one ultrasound device to another. This allows for normal values obtained with one device to be used with other devices, which is an important step forward toward the use of quantitative muscle ultrasound in daily clinical care. Muscle Nerve, 2009

Motor unit number index (MUNIX) versus motor unit number estimation (MUNE): a direct comparison in a longitudinal study of ALS patients.

OBJECTIVE To evaluate how the motor unit number index (MUNIX) is related to high-density motor unit number estimation (HD-MUNE) in healthy controls and patients with amyotrophic lateral sclerosis (ALS). METHODS Both MUNIX and HD-MUNE were performed on the thenar muscles in 18 ALS patients and 24 healthy controls. Patients were measured at baseline, within 2 weeks, and after 4 and 8 months. Clinical evaluation included Medical Research Council (MRC) scale and the ALS functional rating scale (ALSFRS). RESULTS There was a significant positive correlation between MUNE and MUNIX values in ALS patients (r=0.49 at baseline; r=0.56 at 4 months; r=0.56 at 8 months, all p<0.05), but not in healthy controls. After 8 months, both MUNE and MUNIX values of the ALS patients decreased significantly more compared to MRC scale, ALS functional rating scale (ALSFRS) and compound muscle action potential (CMAP) (p<0.05). There was no significant difference in relative decline of MUNIX and HD-MUNE values. CONCLUSIONS In ALS patients, MUNIX and HD-MUNE are significantly correlated. MUNIX has an almost equivalent potential in detecting motor neuron loss compared to HD-MUNE. SIGNIFICANCE MUNIX could serve as a reliable and sensitive marker for monitoring disease progression in ALS.

Muscles alive: Ultrasound detects fibrillations

OBJECTIVE Muscle ultrasound is capable of visualizing muscle movements. Recent improvements in ultrasound technology have raised the question whether it is also possible to detect small-scale spontaneous muscle activity such as denervation. In this study we investigated the ability of dynamic muscle ultrasound to detect fibrillations. METHODS Eight patients with fibrillations were measured simultaneously by ultrasound and EMG to verify which movements on ultrasound examination corresponded to fibrillation potentials on EMG. The temperature dependency of ultrasound detected fibrillations and the observer agreement was assessed in five healthy subjects with focal denervation induced by botulinum toxin. RESULTS Fibrillations appeared on ultrasound examination as small, irregularly oscillating movements within the muscle while the overall shape of the muscle remains undisturbed. Visibility of fibrillations with ultrasound decreased with lower temperatures, with a 32% decrease at 30 degrees C compared to 39 degrees C. The interobserver agreement was substantial with a kappa of 0.65 for experienced observers. CONCLUSION Fibrillations could be visualized with ultrasound. Consistent results could be obtained from trained observers. Care has to be taken to ensure an optimal muscle temperature to avoid false negative results, especially in distal muscles. SIGNIFICANCE Visualization of fibrillations by muscle ultrasound opens the way for a new diagnostic application of this technique.

Motor unit action potential topography and its use in motor unit number estimation.

High‐density multichannel electromyography (EMG) recordings add spatial information to the temporal information content of the surface EMG (sEMG) signal. This study explores the potential value of such multichannel information at a single motor unit level, in particular for the improvement of motor unit number estimation (MUNE) techniques. It is shown that multichannel recordings make it easier to distinguish motor unit action potentials (MUAPs) and that MUAP combinations can be better resolved. Furthermore, the spatiotemporal information allows a quantitative assessment of the representativity of the mean of the recorded MUAPs in relation to the maximum CMAP, i.e., for the muscle as a whole. In general, this is practically impossible on the basis of temporal information alone. For these reasons, we expect that high‐density sEMG has the potential to address several methodological limitations of single channel surface EMG recordings. This is specifically illustrated in this study for one of the MUNE techniques in use, the F‐response method. Muscle Nerve, 2005

Motor Unit Number Index (MUNIX): reference values of five different muscles in healthy subjects from a multi-centre study.

Motor Unit Number Index (MUNIX) : Reference values of five different muscles in healthy subjects from a multi-centre study

Motor unit tracking with high-density surface EMG

Following (tracking) individual motor units over time can provide important new insights, both into the relationships among various motor unit (MU) morphological and functional properties and into how these properties are influenced by neuromuscular disorders or interventions. The present study aimed to determine whether high-density surface EMG (HD-sEMG) recordings, which use an array of surface electrodes over a muscle, can increase the yield of MU tracking studies in terms of the number of MUs that can be tracked. For that purpose, four HD-sEMG recording sessions were performed on the thenar muscles of ten healthy subjects. Decomposition of the recorded composite responses yielded a study total of 2849 motor unit action potentials (MUAPs). MUAPs that were found in both of the first two sessions, performed on the same day, were defined as trackable MUAPs. Our results show that 22 (median value; range, 13-34) MUAPs per nerve were trackable, which represented approximately 5% of the total MU population. Of these trackable MUAPs, 16 (11-26) could also be found in one or both of the third and fourth sessions, which were performed between 1 and 13 weeks after the initial studies. Nine (4-18) MUAPs were found in all four sessions. Many of the characteristic MUAP shapes matched well between sessions, even when these sessions were several weeks apart. However, some MUAPs seem very sensitive to changes in arm position or in the muscles morphology (e.g., to changes in muscle fiber length due to variable degrees of thumb flexion or extension), particularly those from larger and/or superficial MUs. Standardization is, therefore, essential to detect even small MUAP changes, as may occur with pathology or interventions. If this is accomplished, MU tracking with HD-sEMG may prove to be a powerful tool for a promising type of neurophysiological investigation.

Monitoring disease progression using high-density motor unit number estimation in amyotrophic lateral sclerosis

In amyotrophic lateral sclerosis (ALS), progressive motor neuron loss causes severe weakness. Functional measurements tend to underestimate the underlying pathology because of collateral reinnervation. A more direct marker of lower motor neuron loss is of significant importance. We evaluated high‐density motor unit number estimation (MUNE), as compared with the ALS Functional Rating Scale (ALSFRS) and maximal compound muscle action potential (CMAP) amplitude, for monitoring and classifying disease progression. MUNE showed good reproducibility (intraclass correlation coefficient = 0.86). MUNE showed a significantly greater decrease than the ALSFRS, the Medical Research Council (MRC) scale, and CMAP amplitude. Patients could be stratified into groups with rapidly or slowly progressive disease based on a decrement in MUNE at 4 months from baseline; ALSFRS score at 8 months was significantly lower in the rapidly progressive group. MUNE was sensitive to motor neuron loss early in the disease course when compared to other clinical measures. Stratification of patients based on a decrease in MUNE seems feasible. Muscle Nerve, 2010

Quantitative facial muscle ultrasound: Feasibility and reproducibility

In this study we describe a protocol for quantitative ultrasound of facial muscles (procerus, zygomaticus major, levator labii superior, depressor anguli oris, mentalis, orbicularis oris pars labialis, orbicularis oris pars marginalis). Methods: Muscle thickness (MT) and echo intensity (EI) were measured in 12 healthy subjects and a myotonic dystrophy type 1 patient. Results: MTs ranged from 0.15 to 0.30 mm, except for the procerus muscle (0.06 mm). EIs ranged from 1 to 34, except for the procerus muscle. MT reproducibility was fair for the orbicularis oris pars labialis, excellent for the procerus and levator labii, and good for the other muscles. The myotonic dystrophy type 1 patient showed high EIs, outside the range in healthy subjects in 6 of the 7 muscles. MT was lower than the range seen in healthy subjects in 4 muscles. Conclusion: Quantitative muscle ultrasound of the facial muscles is feasible and shows moderate to excellent reproducibility. Muscle Nerve 48: 375–380, 2013