Ilse M.P. Arts

Skeletal Muscle Ultrasound: Correlation Between Fibrous Tissue and Echo Intensity

In this study, we examined the correlation between muscle ultrasound and muscle structure. Echo intensity (EI) of 14 muscles of two golden retriever muscular dystrophy dogs was correlated to the percentage interstitial fibrous tissue and fat in muscle biopsy. A significant correlation between interstitial fibrous tissue and EI was found (r = 0.87; p < 0.001). The separate influence of interstitial fat on muscle EI could not be established as only little fat was present. We conclude that fibrous tissue causes increased muscle EI. The high correlation between interstitial fibrous tissue and EI makes ultrasound a reliable method to determine severity of structural muscle changes.

Normal values for quantitative muscle ultrasonography in adults.

Ultrasonography can detect structural muscle changes caused by neuromuscular disease. Quantitative analysis is the preferred method to determine if ultrasound findings are within normal limits, but normative data are incomplete. The purpose of this study was to provide normative muscle ultrasonography data for muscle thickness and echo intensity for five different muscle groups in adults. Bilateral scans of the sternocleidomastoid, biceps brachii/brachialis, forearm flexor group, quadriceps femoris, and tibialis anterior were made in 95 volunteers, aged 17–90 years. Both muscle thickness and echo intensity showed gender differences and a muscle‐specific non‐linear correlation with age. The muscles of the upper extremities showed right–left differences. These data demonstrate the effect of age on muscle characteristics and provide normative values that can be used in clinical practice. Muscle Nerve, 2010

Muscle ultrasonography: a diagnostic tool for amyotrophic lateral sclerosis.

OBJECTIVE In a prospective study we tested whether muscle ultrasonography can differentiate between amyotrophic lateral sclerosis (ALS) and mimics. Furthermore, we assessed the ability of ultrasonography to identify subclinical lower motor neuron involvement. METHODS In 59 patients, suspected for adult onset motor neuron disease, ultrasound scans were made of 12 different muscle groups. Echo intensity was determined and each muscle was screened for fasciculations. Ultrasonography was considered diagnostic for ALS when echo intensity was 1.5 SD above normal in at least two muscles and fasciculations were present in at least four muscles. RESULTS Ultrasonography differentiated between ALS and mimics with 96% sensitivity and 84% specificity. In the 27 ALS patients, ultrasonography detected 15 regions with lower motor neuron involvement that were negative using either clinical examination or needle EMG. CONCLUSIONS Muscle ultrasound can differentiate between amyotrophic lateral sclerosis and mimics with high sensitivity and specificity, and is a sensitive tool to screen for regional lower motor neuron involvement. SIGNIFICANCE Muscle ultrasonography is a promising tool in the diagnostic work up of ALS.

Muscle changes in amyotrophic lateral sclerosis: A longitudinal ultrasonography study

OBJECTIVE We performed a longitudinal study to assess structural muscle changes in amyotrophic lateral sclerosis (ALS) using ultrasonography. METHODS During a follow-up of 6 months, ultrasonography parameters (muscle thickness, echo intensity and fasciculations) were obtained from 6 muscle groups in 31 ALS patients, together with strength and scores on the revised ALS functional rating scale (ALSFRS-r). RESULTS At baseline, we found an increased echo intensity and decreased thickness, and these parameters correlated with lower strength. Moreover, ultrasound abnormalities were also detected in muscles with preserved strength. Longitudinal changes in echo intensity, muscle thickness and fasciculations showed large variations between patients. Rates of change in ultrasound parameters did not correlate with changes in ALSFRS-r or strength. CONCLUSION In patients with ALS ultrasound abnormalities can be found in muscles with preserved strength. The pattern of ultrasonographic muscle changes in ALS is highly variable and shows no evident correlation with functional measures. SIGNIFICANCE Ultrasonography is not suitable to monitor 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.

RISE AND FALL OF SKELETAL MUSCLE SIZE OVER THE ENTIRE LIFE SPAN

history of coronary heart disease. The mean Epworth Sleepiness Scale score was 14.4 in persons with sleep apnea, compared with 10.3 in persons without sleep apnea. After controlling for variables associated with falls, sleep apnea, but not snoring, witnessed apnea, or an Epworth Score above 10, was associated with a greater risk of two or more falls during the previous 12 months (odds ratio (OR) 5 2.23, 95% confidence interval (CI) 5 1.11–4.47). Sleep apnea was also associated with a higher Geriatric Depression Scale score (third tertile vs rest, OR 5 2.26, 95% CI 5 1.14–4.48), and inclusion of the depression variable into the model attenuated the relationship between sleep apnea and falls. Including the MMSE score did not substantially alter these results (Table 1). To our knowledge, this is the first study examining the relationship between sleep apnea and falls in older persons. We demonstrated a doubling of the likelihood of falls in older persons with a previous diagnosis of sleep apnea. Hypoxemia and sleep disruption from sleep apnea are related to daytime functional impairments in executive function, vigilance, alertness, fine motor coordination, and psychological disturbance, which may be likely mechanisms. In our population, depression attenuated the magnitude of the association between sleep apnea and falls, suggesting that psychological disturbance may be one of the intermediary factors in the association between sleep apnea and falls. A relationship was not demonstrated between falls and our measure of daytime sleepiness, the Epworth Sleepiness Score, although this score does not differentiate underlying causes resulting in daytime sleepiness. Confirmation of our findings in other elderly populations would be useful, given aging population trends and the high burden from recurrent falls on health and community services.

Muscle ultrasonography to predict survival in amyotrophic lateral sclerosis

The authors assessed the prognostic value of muscle ultrasonography in 31 patients with amyotrophic lateral sclerosis (ALS) and compared it with accepted prognostic variables like functional capacity (measured with the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS)) and muscle strength. Each patient was examined once. The following ultrasonography parameters were determined: muscle thickness, echo intensity (EI) and the presence of fasciculations. Correlations between baseline measurements, preslope values and survival were calculated. EI, disease duration, muscle strength preslope and ALSFRS-R preslope correlated with survival. Using a stepwise multivariate analysis, the combination of EI preslope and ALSFRS-R preslope was shown to have the best predictive value for survival.

Prevalence and distribution of fasciculations in healthy adults: Effect of age, caffeine consumption and exercise

Our objective was to determine the prevalence and distribution of fasciculations in healthy adults and to assess the effect of age, caffeine and exercise. Fasciculations were studied with ultrasonography in 58 healthy adults in various age categories. Questionnaires were used to determine effect of caffeine and regular exercise on the presence of fasciculations. Finally, we tested the effect of strenuous exercise on fasciculations in 10 healthy adults. Twenty-five subjects (43%) showed fasciculations on ultrasonography, mostly in the abductor hallucis longus muscle. Fasciculations were only sporadically encountered in muscle groups above the knee. Subjects with fasciculations were significantly older than those without. Caffeine and regular physical exercise did not influence the prevalence of fasciculations. However, strenuous physical exercise caused a temporary increase in fasciculations, but only in lower leg muscles. Fasciculations above the knee should raise suspicion and may warrant further investigation.

Fasciculations and their F-response revisited: High-density surface EMG in ALS and benign fasciculations

OBJECTIVE To compare the prevalence of fasciculation potentials (FPs) with F-responses between patients with amyotrophic lateral sclerosis (ALS) and patients with benign fasciculations. METHODS In seven patients with ALS and seven patients with benign fasciculations, high-density surface EMG was recorded for 15 min from the gastrocnemius muscle. Template matching was used to search for pairs of FPs with a repetition within 10-110 ms. RESULTS Interspike interval (ISI) histograms were constructed from 282 pairs of benign fasciculations and from 337 FP pairs in ALS. Peaks attributable to F-waves were found at latencies of 32 ms (benign) and 35 ms (ALS). Five patients with benign fasciculations and four patients with ALS had FPs with F-waves. CONCLUSIONS F-waves of FPs occur in both conditions - therefore they are not diagnostically helpful. SIGNIFICANCE F-waves confirm the distal origin of FPs for an individual axon. The occurrence of these FPs in a benign condition suggests that the generation of ectopic discharges in the distal axons is not specific to progressive neurodegeneration.

Intramuscular fibrous tissue determines muscle echo intensity in amyotrophic lateral sclerosis

Ultrasound is a rapidly evolving technique that can be used in the diagnostic work-up of neuromuscular disorders. Affected muscles show diminished muscle thickness and increased echo intensity (EI). Previous studies have shown that fat and fibrous tissue each can increase EI. However, the exact cause of increased echo intensity is not fully known. We compared the findings of an in vivo quantitative muscle ultrasound study with the postmortem histopathological examination of a 62-year-old woman who had amyotrophic lateral sclerosis (ALS). This patient died 27 months after symptom onset. On autopsy, the diagnosis of ALS was confirmed. Transverse ultrasound scans and total cross-sectional muscle specimens of nine different muscles were taken from the same standardized anatomical sites (Fig. 1). Autopsy was performed with the informed consent of the patient within 12 hours after death. Muscle specimens were fixed in 4% formalin; the fibers were orientated transversely for embedding in paraffin. The largest cross-sectional area of each sample was selected and cut in 4-lm-thick sections, which were stained with Masson trichrome. The percentages of perimysial and endomysial tissue and the percentage of interstitial fat were determined by digital image analysis. Ultrasound examinations were performed 3 months before the patient’s death. Details of the standardized protocol and system settings have been described elsewhere. EI was determined quantitatively using histogram analysis, where the mean gray value of the muscle is expressed as a value between 0 (1⁄4 black) and 255 (1⁄4 white). We found that EI was increased in all muscles (mean 73, range 52–91) to about twice the normal value (range 28–42). Histological examination showed a comparable percentage of intramuscular fat (median 8.6%, range 4.9– 16.2%) and fibrous tissue (12.5%, range 6.7–28.5%; Fig. 1D). Fibrous tissue seemed to be more evenly distributed within the muscle, whereas fat was seen in small collections (Fig. 1C). The sternocleidomastoid muscle was considered an outlier and was not used for calculation of correlations. EI was strongly correlated with fibrous tissue (r 1⁄4 0.86, P 1⁄4 0.007; Fig. 1D), and this correlation remained after correction for fat content (r 1⁄4 0.81, P 1⁄4 0.026). EI and the amount of fatty tissue were not correlated (r 1⁄4 0.46, P 1⁄4 0.248), nor was there a correlation after correction for fibrous tissue (r 1⁄4 0.07, P 1⁄4 0.886). In both this study of a human neurogenic disorder and in a study of canine muscular dystrophy, fibrous tissue was the main contributing factor to increased muscle EI. However, other studies have indicated that intramuscular fat also contributes to increased EI, as shown in patients with inflammatory myopathies, in those with little or no fibrous tissue, and in obese subjects. In this study the amounts of fibrous and fatty tissue were comparable, making it possible to study the influence of both variables on EI simultaneously. The influence of fibrous tissue on EI appeared to be stronger than that of fat, possibly due to differences in their distribution within the muscle. Overall, this suggests that fibrosis is the most important determinant of muscle EI in ALS.