Comparison of changes in skeletal muscle mass after stroke categorized by the severity of motor dysfunction: a retrospective study

Abstract

[Purpose] To compare changes in skeletal muscle mass after stroke based on the severity of motor dysfunction. [Participants and Methods] This study included 17 patients who had experienced a stroke. Patients were classified into two groups based on lower limb Brunnstrom stages, i.e., those with stages III and IV (moderate motor dysfunction group; n=9), and those with stages V and VI (mild motor dysfunction group; n=8). Muscle mass was measured at the following time points: within 3 days of stroke onset; at 2 weeks ± 2 days after stroke onset; at 4 weeks ± 2 days after stroke onset; at 8 weeks ± 2 days after stroke onset, and muscle mass indices, i.e., the skeletal muscle mass index (SMI), paralyzed lower limb muscle mass, and non-paralyzed lower limb muscle mass were evaluated. Changes in these muscle mass indices between stroke onset and at 2, 4, and 8 weeks after stroke, i.e., ΔSMI, Δparalyzed lower limb muscle mass, and Δnon-paralyzed lower limb muscle mass, were calculated and the changes in each index over time were compared between the two groups. [Results] The analyses did not reveal any significant intergroup differences. [Conclusion] Even in cases of severe paralysis, appropriate nutritional and exercise therapies may help maintain the muscle mass.

INTRODUCTION

Muscle strength is strongly associated with activities of daily living such as transferring and walking in patients with a stroke; therefore, maintaining and increasing skeletal muscle mass is important^{1, 2)}. The prevalence of sarcopenia in patients with a stroke is 42%³⁾, and they are more likely to lose skeletal muscle mass than elderly people, among whom the sarcopenia prevalence is 10–27%⁴⁾. Furthermore, 50% of patients with a stroke have sarcopenia during the subacute phase; therefore, skeletal muscle loss must be addressed during physical therapy⁵⁾.

Multiple factors are believed to contribute to sarcopenia after a stroke. It is associated with malnutrition due to dysphagia⁶⁾, immobility and decreased physical activity due to ADL disorder⁷⁾, denervation⁸⁾, systemic inflammation associated with cachexia⁹⁾, and an imbalance of catabolism and anabolism¹⁰⁾. An effective method for inhibiting the progression of stroke-related sarcopenia has yet to be established. However, it has been reported that combining essential amino acid supplementation¹¹⁾, whey protein combined with vitamin D supplementation¹²⁾, a high-calorie diet¹³⁾, avoidance of multiple drug use¹⁴⁾, increased physical activity levels¹⁵⁾, and reduction in sedentary lifestyle¹⁶⁾ may prevent sarcopenia. The prevalence of stroke-related sarcopenia tends to increase during the acute phase of stroke¹⁷⁾, and a significant decrease in skeletal muscle mass has been reported three weeks after a stroke¹⁸⁾. Therefore, it is important to investigate muscle mass in patients with acute stroke. There are many diseases that cause muscle loss due to damage to upper motor neurons, such as spinal cord injury and amyotrophic lateral sclerosis. Therefore, it is highly likely that the decrease in alpha motor neurons or number of motor units is involved in the decrease in muscle mass¹⁹⁾, and it is expected that the more severe the stroke, the faster the progression of decreasing of muscle, but no such research has been conducted. It is hypothesized that severe corticospinal tract injury causes a dramatic decline in skeletal muscle mass. However, few longitudinal studies have been conducted on muscle mass in patients with acute stroke. It is unclear whether muscle mass is more likely to decrease with more severe motor paralysis. This study aimed to compare changes in skeletal muscle mass after stroke according to the severity of motor dysfunction.

PARTICIPANTS AND METHODS

The participants were 17 patients with a stroke who were hospitalized at the Hirosaki Stroke Rehabilitation Center between September 2019 and September 2021 and met the following conditions: eight male and nine female patients; five patients with cerebral hemorrhage, twelve with cerebral infarction; age 73.6 ± 11.2 years; height 157.9 ± 10.3 cm; weight 60.2 ± 11.4 kg (mean ± standard deviation) (Table 1). Exclusions included those with lower extremity Brunnstrom stage (Br.stage) II or lower at the time of stroke onset, those with poor nutritional status (serum albumin level less than 3.5 g/dL), those with a premorbid modified Rankin Scale Score of five points or more, those with an implanted pacemaker, those with physical defects, and those that could not be examined in the supine position for several minutes without moving due to joint contracture, dementia, or altered consciousness. This retrospective study was conducted using the medical records of participants.

Table 1. Attributes and Brunnstrom stage, ADL, diet and nutrition, rehabilitation time of participants tributes of participants.

Attributes	Total participants	Mild motor dysfunction group	Moderate motord ysfunction group
Gender (Num) (male/female)	8/9	2/6	6/3
Age (years)	73.6 ± 11.2	76.0 ± 9.8	71.4 ± 9.8
Height (cm)	157.9 ± 10.3	155.2 ± 10.2	160.3 ± 9.8
Weight (kg)	60.2 ± 11.4	58.9 ± 5.9	61.5 ± 14.9
Stroke type (hemorrhage/infarction)	5/12	1/7	4/5
Lower limb Br.stage (Num)		Ⅲ: 5, Ⅳ: 4	Ⅴ: 7, Ⅵ: 1
FIM-L at onset (Num)	3/14	2/6	1/8
(above 5 points/below 5 points)
FIM-L at 8 weeks (Num)	8/9	3/5	4/5
(above 5 points/below 5 points)
Serum albumin level (g/dL)	4.2 ± 0.3	4.3 ± 0.3	4.2 ± 0.4
Average meal amount (%)	85	89	82
Average rehabilitation time (min)	127.9	119.8	136
Average physical therapy time (min)	63.7	56.6	70.8

ADL: activities of daily living; Br.stage: Brunnstrom stage; FIM-L: functional independence measure locomotion (walking). Numbers before and after the ± represent the mean and standard deviation.

The study was conducted in accordance with the principles of the Declaration of Helsinki. We paid careful attention to protecting the privacy of information, explained to them that their medical records would be used for research purposes, and obtained their consent before carrying out the study. This study was approved by the Ethics Committee of the Hirosaki Stroke and Rehabilitation Center (approval number: 23B002). The author classified lower limb Br.stage III and IV into the moderate motor dysfunction group (9 participants), and Br.stage V and VI into the mild motor dysfunction group (8 participants)²⁰⁾. Regarding the participants’ activities of daily living at the time of onset, two participants (out of nine) in the mild dysfunction group and one participant (out of eight) in the moderate dysfunction group scored five or more on the functional independence measure mobility scale. Eight weeks after the onset, three (out of nine) and four (out of eight) participants remained in the mild dysfunction and moderate dysfunction groups, respectively. Body composition was measured using the medical body composition analyzer called In Body s10 (manufactured by InBody, Seoul, South Korea). The authors assessed the skeletal muscle mass index (SMI), paralyzed lower limb muscle mass, and non-paralyzed lower limb muscle mass using the collected data. Basic information, such as age, weight, and height, was acquired from medical records. Measurements were performed within three days, 2 weeks ± 2 days, 4 weeks ± 2 days, and 8 weeks ± 2 days of onset. The test was conducted 4–6 hours after lunch. To eliminate the effect of each participant’s initial muscle mass, the differences between the muscle mass indices at onset and at 2, 4, and 8 weeks were calculated. The obtained data were called ΔSMI, Δparalyzed lower limb muscle mass, and Δnon-paralyzed lower limb muscle mass. The authors compared the changes in each index over time between the two groups. Statistical analysis was performed by analysis of variance using multiple split plots, with group (moderate motor dysfunction group and mild motor dysfunction group) and time as the factors. To check for the presence of selection bias, the height, weight, type of stroke, nutritional status, sex, FIM walking ability (walking) at onset, FIM walking ability (walking) 8 weeks later, serum albumin level, rehabilitation time, and average physical therapy time of both groups were compared using two-sample t-test or Mann–Whitney U test after confirming normality with the Shapiro–Wilk test. The significance level was set at 5%. R4.2.1 statistical software (University of Auckland, Auckland City, New Zealand) was used for the analysis. The sample was estimated using G*Power 3.1.9.7 (Heinrich Heine University, Düsseldorf, Germany), with a large effect size of 0.4, alpha error of 0.05, power (1−β): 0.8, number of groups: 2, number of measurements: 3, Corr of rep measurements: 0.5, non-sphericity correction (ε): 1. Based on the results, a minimum sample size of 12 participants was determined. The rehabilitation program was tailored to each patient’s body dysfunction. For example, physical therapy included the facilitation of paralyzed limb exercises, range-of-motion exercises, gait training, and task-oriented training. The participants underwent daily rehabilitation, the amount of which was adjusted by a therapist depending on their body dysfunction and condition. In this study, rehabilitation program didn’t standardize. The above training program was confirmed by referring to the medical records. The average rehabilitation time was 119.8 minutes for the mild dysfunction group and 136 minutes for the moderate dysfunction group, and the average duration of physical therapy was 56.6 minutes for the mild dysfunction group and 70.8 minutes for the moderate dysfunction group.

RESULTS

The average values for both groups were as follows: In the moderate motor dysfunction group, the Δ2 weeks SMI was −0.13 kg/m², the Δ4 weeks SMI was −0.28 kg/m², and the Δ8 weeks SMI was −0.31 kg/m². In the mild motor dysfunction group, the Δ2 weeks SMI was 0.06 kg/m², the Δ4 weeks SMI was 0.04 kg/m², and the Δ8 weeks SMI was 0.14 kg/m².

Regarding the muscle mass of the lower limb on the non-paralyzed side, in the moderate motor dysfunction group, the Δ2 weeks value was 0.12 kg, Δ4 weeks was −0.03 kg, and Δ8 weeks was −0.05 kg. In the mild motor dysfunction group, the Δ2 weeks was 0 kg, Δ4 weeks was 0.18 kg, and Δ8 weeks was 0.20 kg.

Regarding the muscle mass of the paralyzed lower limb, In the moderate motor dysfunction group, the Δ2 weeks was 0.08 kg, Δ4 weeks was −0.02 kg, and Δ8 weeks was 0.02 kg. In the mild motor dysfunction group, the Δ2 weeks was −0.02 (kg), Δ4 weeks was 0.22 kg, and Δ8 weeks was 0.24 kg. (Table 2)

Table 2. Progress of SMI and muscle mass change in lower limbs.

	Δ2 weeks	Δ4 weeks	Δ8 weeks
Mild motor dysfunction group
SMI (kg/m2)	0.06	0.04	0.14
muscle mass of the non-paralyzed lower limb (kg)	0	0.18	0.2
muscle mass of the paralyzed lower limb (kg)	−0.02	0.22	0.24
Moderate motor dysfunction group
SMI (kg/m2)	−0.13	−0.28	−0.31
muscle mass of the non-paralyzed lower limb (kg)	0.12	0.03	−0.05
muscle mass of the paralyzed lower limb (kg)	0.08	−0.02	0.02

SMI: skeletal muscle mass index. Δ represents the amount of change.

In statistical analysis, there were no significant differences in age, height, weight, stroke type, nutritional status, gender, FIM Locomotion (Walking) at onset, FIM Locomotion (Walking) at 8 weeks, Serum albumin level, rehabilitation time, Average physical therapy time between the two groups. Analysis of variance using multiple partition plots showed no significant differences in SMI, lower limb muscle mass on the paralyzed side, or lower limb muscle mass on the non-paralyzed side between the two groups.

DISCUSSION

Previous studies have reported a relationship between sarcopenia and a decrease in alpha motor neurons, and between corticospinal tract damage and alpha motor neurons^{19, 21)}. Therefore, it may be that the more severe the corticospinal damage, the more severe the stroke-related sarcopenia. To the best of our knowledge, this is the first attempt to classify stroke patients by severity using a hemiplegic functional test and longitudinally investigate changes in muscle mass. No significant differences were observed between the two groups. The author initially hypothesized that the SMI and muscle mass of the paralyzed lower limb and muscle mass of the non-paralyzed lower limb would gradually decrease over time in both groups, with the moderate group showing a greater decrease in muscle mass. However, the results did not show any significant differences between the groups. Previous studies have shown that the prevalence of sarcopenia is 15.8% before stroke onset, 29.5% on the 10th day, and 51.6% 4 weeks after stroke, and it is believed to increase by approximately 15% from before stroke to 10 days and by approximately 20% from 10 days to 4 weeks after stroke¹⁷⁾. Additionally, muscle weakness in the unaffected limbs may occur within a week of stroke²²⁾. The results of this study showed that there was almost no decrease in SMI in either group or tendency for an increase in the muscle mass of the paralyzed lower limb. Although this is inconsistent with the results of the present study, muscle mass may vary depending on nutritional status, physical activity level, and training status²³⁾. It has been reported that the effects of stroke-related sarcopenia in patients with a stroke in the subacute stage can be improved by 21.9% through exercise therapy centered on standing training, suggesting that exercise therapy can increase muscle mass in patients with a stroke²⁴⁾. In this case, suggesting the possibility that active use of the lower limb through standing and walking exercises may maintain and improve muscle mass in the paralyzed lower limb. Although muscle weakness due to hemiplegia is believed to be largely due to central cortical activation disorders, Miller reported that central activation deficits cannot fully explain muscle weakness and speculated that structural or functional neuromuscular organization defects, such as muscle atrophy, contribute to weakness in hemiplegic muscles after stroke²⁵⁾. In this study, it is possible that even if the motor paralysis is severe, the effects of muscle loss due to denervation may not be evident in the acute and subacute stages. This study has some limitations. Because the participants were receiving intravenous treatment depending on the stage and because of factors such as impaired consciousness or urinary function, it was not possible to ensure that all participants defecated prior to the body composition measurement, thereby affecting the result. The changes in muscle mass of each patient may have been influenced by the type and amount of rehabilitation. There was no significant difference in gender and stroke type, but it seems the number is biased, so no difference may be due to the sample size. Although β-blocker and Anti-inflammatory drugs are not effective¹⁹⁾, stroke related sarcopenia may be associated with oral and intravenous treatment¹⁴⁾.

I found no statistically significant differences in the muscle mass of patients with a stroke when they were classified according to stroke-related motor dysfunction. Even if paralysis is severe, muscle mass may be maintained appropriate nutritional and exercise therapies.

Conflicts of interest

The authors have no conflicts of interest to report.