Serial sarcomere number is substantially decreased within the paretic biceps brachii in individuals with chronic hemiparetic stroke.

A muscle's structure, or architecture, is indicative of its function and is plastic; changes in input to or use of the muscle alter its architecture. Stroke-induced neural deficits substantially alter both input to and usage of individual muscles. We combined in vivo imaging methods (second-harmonic generation microendoscopy, extended field-of-view ultrasound, and fat-suppression MRI) to quantify functionally meaningful architecture parameters in the biceps brachii of both limbs of individuals with chronic hemiparetic stroke and in age-matched, unimpaired controls. Specifically, serial sarcomere number (SSN) and physiological cross-sectional area (PCSA) were calculated from data collected at three anatomical scales: sarcomere length, fascicle length, and muscle volume. The interlimb differences in SSN and PCSA were significantly larger for stroke participants than for participants without stroke (P = 0.0126 and P = 0.0042, respectively), suggesting we observed muscle adaptations associated with stroke rather than natural interlimb variability. The paretic biceps brachii had ∼8,200 fewer serial sarcomeres and ∼2 cm2 smaller PCSA on average than the contralateral limb (both P < 0.0001). This was manifested by substantially smaller muscle volumes (112 versus 163 cm3), significantly shorter fascicles (11.0 versus 14.0 cm; P < 0.0001), and comparable sarcomere lengths (3.55 versus 3.59 µm; P = 0.6151) between limbs. Most notably, this study provides direct evidence of the loss of serial sarcomeres in human muscle observed in a population with neural impairments that lead to disuse and chronically place the affected muscle at a shortened position. This adaptation is consistent with functional consequences (increased passive resistance to elbow extension) that would amplify already problematic, neurally driven motor impairments.

Electrical impedance myography in the assessment of disuse atrophy.

UNLABELLED: Tarulli AW, Duggal N, Esper GJ, Garmirian LP, Fogerson PM, Lin CH, Rutkove SB. Electrical impedance myography in the assessment of disuse atrophy. OBJECTIVE: To quantify disuse atrophy using electrical impedance myography (EIM), a noninvasive technique that we have used successfully to study neurogenic and myopathic atrophy. DESIGN: We performed EIM of the tibialis anterior of subjects with disuse atrophy secondary to cast immobilization and in their contralateral normal leg. Subjects were studied shortly after cast removal and again several weeks to months after the cast was removed and normal mobility was restored. SETTING: Outpatient neurology and orthopedic practices at a tertiary care medical center. PARTICIPANTS: Otherwise healthy subjects (N=10) with unilateral leg fracture. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Resistance, reactance, and phase measured at 50kHz. RESULTS: The main EIM outcome parameter, phase at 50kHz, was lower in the immobilized leg in 9 of 10 cases. Additionally, when normal mobility was restored, the phase of the casted leg increased relative to its initial measurement in all 10 cases, while it increased inconsistently in the contralateral leg. CONCLUSIONS: EIM may be a powerful tool for the assessment of disuse atrophy.

Localized muscle impedance abnormalities in amyotrophic lateral sclerosis.

OBJECTIVES: To assess changes in electrical impedance myography (EIM) parameters in amyotrophic lateral sclerosis (ALS). METHODS: Ten patients with ALS and a cohort of normal subjects underwent EIM testing of tibialis anterior. Montages using voltage and current electrodes placed at a distance (far) and in close proximity (near) were compared. The EIM parameters, resistance (R), reactance (X), and phase (theta) in the patients with ALS, were compared with normal values. RESULTS: theta measured at 50 kHz using the near montage was most sensitive to the presence of ALS, with 9 of 10 patients with ALS having smaller theta values than the calculated lower limit of normal. theta using the far montage and X using both the near and far montages were also sensitive to disease, whereas R did not seem to be useful. CONCLUSION: EIM is sensitive to muscle abnormalities in ALS, with theta measured with near montages providing the best results.

Impaired distal thermoregulation in diabetes and diabetic polyneuropathy.

OBJECTIVE: To determine how thermoregulation of the feet is affected by diabetes and diabetic polyneuropathy in both wakefulness and sleep. RESEARCH DESIGN AND METHODS: Normal subjects, diabetic subjects without neuropathy, diabetic subjects with small-fiber diabetic polyneuropathy, and those with advanced diabetic polyneuropathy were categorized based on neurological examination, nerve conduction studies, and quantitative sensory testing. Subjects underwent foot temperature monitoring using an iButton device attached to the foot and a second iButton for recording of ambient temperature. Socks and footwear were standardized, and subjects maintained an activity diary. Data were collected over a 32-h period and analyzed. RESULTS: A total of 39 normal subjects, 28 patients with diabetes but without diabetic polyneuropathy, 14 patients with isolated small-fiber diabetic polyneuropathy, and 27 patients with more advanced diabetic polyneuropathy participated. No consistent differences in foot temperature regulation between the four groups were identified during wakefulness. During sleep, however, multiple metrics revealed significant abnormalities in the diabetic patients. These included reduced mean foot temperature (P < 0.001), reduced maximal temperature (P < 0.001), increased rate of cooling (P < 0.001), as well as increased frequency of variation (P = 0.005), supporting that patients with diabetic polyneuropathy and even those with only diabetes but no diabetic polyneuropathy have impaired nocturnal thermoregulation. CONCLUSIONS: Nocturnal foot thermoregulation is impaired in patients with diabetes and diabetic polyneuropathy. Because neurons are highly temperature sensitive and because foot warming is part of the normal biology of sleep onset and maintenance, these findings suggest new potentially treatable mechanisms of diabetes-associated nocturnal pain and sleep disturbance.

Discriminating neurogenic from myopathic disease via measurement of muscle anisotropy.

Skeletal muscle is electrically anisotropic, with a tendency for applied electrical current to flow more readily along muscle fibers than across them. In this study, we assessed a method for non-invasive measurement of anisotropy to determine its potential to serve as a new technique for distinguishing neurogenic from myopathic disease. Measurements were made on the biceps brachii and tibialis anterior muscles in 15 normal subjects and 12 patients with neuromuscular disease (6 with amyotrophic lateral sclerosis and 6 with various myopathies) using 50 kHZ applied current. Consistent multi-angle anisotropic patterns were found for reactance and phase in both muscles in normal subjects. Normalized anisotropy differences for each subject were defined, and group average values identified. The amyotrophic lateral sclerosis (ALS) patients demonstrated increased and distorted anisotropy patterns, whereas myopathic patients demonstrated normal or reduced anisotropy. These results suggest that non-invasive measurement of muscle anisotropy has potential for diagnosis of neuromuscular diseases.

Reference values for 50-kHZ electrical impedance myography.

Electrical impedance myography (EIM) is a method for non-invasively and quantitatively assessing muscle health, in which the major outcome parameter, phase (theta), decreases in diseased states. In order to create a set of normal reference values, we performed 50-kHZ EIM in 5 muscles of 87 healthy individuals, using theta as the major outcome variable. Because the distributions of data were mostly skewed, logarithmic transformations were performed, and the resulting data were fitted to quadratic functions. The lower limit of normal was set by plotting the lower 95% confidence interval of the curve for each muscle and then identifying age-specific reference values. We found that the distribution of data was similar to that for other neurophysiologic parameters. The lower limit of normal was easily defined, and relatively few values fell below the proposed lower limit. By using commercially available bioimpedance devices, these values will allow other investigators to explore the application of 50-kHZ EIM in clinical neuromuscular disease research.

Optimizing measurement of the electrical anisotropy of muscle.

Skeletal muscle is electrically anisotropic, with applied high-frequency electrical current flowing more easily along than across muscle fibers. As an early step in harnessing this characteristic for clinical use, we studied approaches for maximizing the measured anisotropy by varying electrode size and applied current frequency in the tibialis anterior of 10 normal subjects. The results were compared to those from two patients with amyotrophic lateral sclerosis (ALS). Current was applied percutaneously, first parallel and then perpendicular to the major fiber direction of the muscle at frequencies ranging from 20 kHZ to 1 MHZ, using a fixed voltage-electrode length and varying the current-electrode length. The measured anisotropy was most pronounced using the longest length current electrodes and with a 125-kHZ applied frequency for the major outcome parameter phase. In addition, the two ALS patients showed very distinct anisotropic patterns. These results support the belief that, with the appropriate measurement technique, non-invasive assessment of electrical anisotropy of muscle may have useful clinical application.