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

Abstract

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.

Keywords: fascicle; imaging; muscle; sarcomere; stroke.

Fig. 1.

SSN/OFL. Data illustrating interlimb differences in SSN and, proportionally, OFL for all participants who had a stroke and the age-range matched controls (no stroke). The average of the calculated parameter value (see Eqs. 4 and 5) for each individual participant is represented by a symbol of different shape/color, and each individual’s limbs are connected by a line. Black filled circles and error bars which are offset from individual participant data represent mean and SE estimated from the GLMM. The asterisk (*) indicates a significant difference (P < 0.05).

Fig. 2.

Fascicle and sarcomere length. Average fascicle length (A) and sarcomere length (B) measurements from both limbs and in all participants in the stroke and control (no stroke) groups. The average of the measured parameter values for each individual participant is represented by a symbol of different shape and or color. Each individual’s limbs are connected by a solid line. Black filled circles and error bars which are offset from individual participant data represent mean and SEs estimated from the GLMM. The asterisk (*) indicates a significant difference (P < 0.05).

Fig. 3.

Muscle volume and PCSA. Biceps brachii muscle volume (with intramuscular fat removed) (A) and calculated PCSA (see Eq. 6) (B) for both limbs of all participants who had a stroke and the age-matched controls (no stroke). The average of the parameter values for each individual participant is represented by a symbol of different shape and or color. Each individual’s limbs are connected by a solid line. Black filled circles and error bars which are offset from individual participant data represent mean and SE estimated of PCSA from the GLMM. In A, the asterisk (*) indicates a significant difference in muscle volume across groups (stroke versus no stroke) established from implementing the Mann–Whitney U test (P < 0.05). In B, the asterisk (*) indicates a significant difference either across (stroke versus no stroke) or within groups (i.e., paretic versus nonparetic) in PCSA estimated from the GLMM (P < 0.05).

Fig. 4.

Interlimb muscle differences poststroke. Average percent difference in muscle architectural parameters, including muscle volume, PCSA, SSN, and sarcomere length (SL) was calculated for all participants included in our study who had experienced a stroke and had smaller muscle volume on the paretic biceps. A positive percent difference indicates that the paretic parameter is smaller than the nonparetic side. Error bars represent one SD from the mean of the percent difference across the subjects.

Fig. 5.

Illustration of experimental set up for muscle architecture measures. (A) Arm posture used for measurement of fascicle length using ultrasound (Right) and for sarcomere length (see B). The white dashed line overlaid on the ultrasound image illustrates a manually segmented muscle fascicle. (B) Illustration of the experimental setup for the Zebrascope, which utilizes second-harmonic generation microendoscopy to capture the natural striation pattern of sarcomeres in vivo. The Biodex chair and arm fixture (Middle) was used for both measurements of sarcomere and fascicle lengths (see A). The microscope is enlarged on the left (blue dashed box) to depict the flow of laser light through the microscope (orange arrows). Below the microscope is a graphic of the probe that is inserted into the muscle. The laser light interacts with myofibrils between the two needles at a location of 1.5 cm from the base of the probe. To the right, a raw image which would be seen during image collection and the same image after postprocessing are shown. Sarcomere length is measured from the processed image; for reference, the length of 10 sarcomeres in series are indicated by a white line. (C) Participant in the supine positioning (Left) in the MRI bore. (Inset) The splinting of the arm to reduce artifacts because of hand and arm movement. (Right) 3D rendering of the biceps brachii muscle and humerus bone with a single MRI slice superimposed.