Effect of action observation training on hand function, upper extremity strength and fatigue in individuals with multiple sclerosis

Abstract

Background

Multiple sclerosis (MS) is a chronic autoimmune condition that affects the central nervous system, frequently resulting in upper limb impairment, which considerably affects activities of daily living and quality of life. Action Observation Training (AOT) is a novel neurorehabilitation method that utilizes the mirror neuron system to improve motor performance. This study aimed to evaluate the effectiveness of AOT in improving hand function, grip strength, and reducing fatigue in individuals with MS.

Methods

A non-randomized, single-blind clinical experiment was conducted involving 30 multiple sclerosis patients, who were allocated to either an intervention group (AOT in conjunction with standard physical therapy) or a control group (standard physical therapy alone). The primary outcome was evaluated utilizing the Arm Function in Multiple Sclerosis Questionnaire (AMSQ). Secondary objectives included grip and pinch strength (assessed by dynamometry) and Fatigue Severity Scale (FSS). Evaluations were conducted at baseline and following four weeks of intervention. Data were evaluated utilizing Analysis of Covariance (ANCOVA) with significance established at p < 0.05.

Results

The intervention group showed significantly greater improvements in AMSQ scores (adjusted mean difference = −29.5, ± 4.5 SE, p < 0.05), power grip strength (MD = 10.54, ± 3.20 SE, p = 0.003 for the affected hand), pinch strength (MD = 1.46, ± 0.45 SE, p = 0.003 for the affected hand), and fatigue (MD = −9.60, ± 4.13 SE, p = 0.028), compared to the control group. These findings suggest that AOT is an effective intervention for improving upper limb function and reducing fatigue in individuals with MS.

Conclusion

AOT significantly improves hand function, grip strength, and fatigue levels in individuals with MS, suggesting its potential as an effective rehabilitation tool. Future investigations should examine the enduring advantages of AOT and its amalgamation with alternative neurorehabilitation methodologies.

Introduction

Multiple sclerosis (MS) is an autoimmune disease and the leading cause of non-traumatic neurological disability in young adults (Browne et al., 2014, Jameson et al., 2018). The prevalence of this disease in the world is estimated at 35.9 per 100,000 people (Walton et al., 2020) more specifically, the prevalence of this disease in Iran is 100 people per 100,000 people (Mirmosayyeb et al., 2022), which is more than twice its prevalence globally.

Upper limb movement disorders are common in patients with multiple sclerosis, and this has a significant impact on people's quality of life (Rocca et al., 2019a). Nearly 75 % of people with MS report experiencing upper limb disability, primarily due to tremors, lack of coordination, and muscle weakness (McDonald and Compston, 2006).

While research on Action Observation Training (AOT) for upper limb dysfunction in MS is still emerging, preliminary studies have shown promise. For instance, a study by Cordani et al. found that AOT led to significant improvements in right-hand strength and motor performance in MS patients and was associated with increased dynamic functional network connectivity in sensorimotor and cognitive networks, suggesting a neurophysiological basis for the observed clinical gains (Cordani et al., 2021a).

For people with MS, where demyelination can disrupt cortical networks, the activity of mirror neurons during action observation may facilitate neuroplasticity and motor learning, potentially helping to reorganize or strengthen alternative neural pathways to improve movement (Tomassini et al., 2012).

Bertoni and colleagues found in their study that 75 % of individuals with MS experience impairments in manual dexterity, even in the early stages of the disease (Bertoni et al., 2015). Dysfunction of the upper limbs of people with MS leads to a decrease in the ability to perform Activities of Daily Living (ADL) (Lamers et al., 2015) which itself reduces the independence and quality of life of the individual (Yozbatıran et al., 2006). Kierkegaard et al. found that manual dexterity is an essential predictor of activity level and overall social participation (Kierkegaard et al., 2012), highlighting how upper limb impairment directly impacts a person's ability to engage with their community and maintain independence.

On the other hand, at least 75 % of individuals with MS have reported experiencing fatigue at some point during the course of the disease (Krupp, 2006, Lerdal et al., 2007). For many individuals, fatigue is reported as the most disabling symptom, even more so than pain and physical disability (Janardhan and Bakshi, 2002). Therefore, it is necessary to find effective ways of rehabilitation to improve the physical condition and fatigue of people with MS.

Various traditional and new methods are used to treat MS. AOT is a new method for upper limb rehabilitation of people with neurological problems (Buccino et al., 2018). This approach, acting through the modulation of the mirror network of neurons, has obtained promising results in improving the function of the upper limb (Rizzolatti and Craighero, 2004). Mirror neurons are a group of neurons that discharge when a person performs a movement or when they observe another person performing a movement (Acharya and Shukla, 2012).

The mirror neuron system plays a critical role in movement recognition, imitation, and learning (Rizzolatti and Arbib, 1998, Cross et al., 2009). By engaging this system, movement learning can be facilitated in individuals with injuries (Buccino et al., 2006). For people with movement disorders caused by damage to the central nervous system, the activity of the cortical networks of mirror neurons facilitates the adaptation of neuroplasticity and therefore movement improvement (Buccino et al., 2006). According to evidence of a relationship between activity in the human primary motor cortex during action observation and the mirror neuron system (Kilner et al., 2009) and reduced functional connectivity in the mirror system of people with MS (Plata-Bello et al., 2017), it appears that action observation may influence the primary motor cortex in individuals with MS.

Since observing a complex and purposeful activity activates the mirror neuron system more than observing a simple activity (Lee and Kim, 2019), one way to further stimulate the mirror neuron system is to use activities aligned with everyday life experiences (Lee and Kim, 2019). Few studies have been reported regarding the impact of action observation on the upper limbs of individuals with MS. Despite acknowledging that many activities of daily living are performed bilaterally (Buccino et al., 2006), the existing studies have only assessed the effect of Action Observation (AO) on the dominant or more severely affected upper limb, using typical movements rather than those based on activities of daily living (Rocca et al., 2019a).

Currently, rehabilitation for upper limb dysfunction in MS often includes conventional physical and occupational therapy, focusing on strengthening, stretching, and task-specific practice. These approaches can have limitations, including patient fatigue, the need for specialized equipment, and variable long-term adherence (Lamers et al., 2016a). Therefore, there is a clear need to explore novel and accessible interventions that can enhance traditional methods.

Therefore, there is still a lack of studies on the use of occupation-based exercises/meaningful activities for people with MS. Because it is believed that one of the ways to increase a person's motivation and participation level is to make their exercises meaningful (Trombly, 1995).

What distinguishes this study is the use of the Arm Function in Multiple Sclerosis Questionnaire (AMSQ) as the primary outcome measure. Unlike prior studies that focused on general motor performance or isolated muscle strength, AMSQ assesses functional ability through real-life upper limb tasks. This focus on functional, occupation-based outcomes aligns with the everyday challenges experienced by individuals with MS and provides clinically meaningful insights into rehabilitation efficacy.

While the systematic review by Lamers et al (Lamers et al., 2016b). provided a broad overview of upper limb rehabilitation in MS, our study offers novel contributions. Specifically, we are among the first to use the Arm Function in Multiple Sclerosis Questionnaire (AMSQ) as a primary outcome, which assesses function through patient-reported performance of daily tasks, providing a more clinically relevant perspective. Furthermore, our intervention is explicitly occupation-based, using meaningful activities of daily living, a focus not systematically evaluated in the studies included in that review. Finally, we concurrently assess the impact of AOT on fatigue (using the FSS), addressing one of the most disabling symptoms of MS alongside motor function. This study represents the inaugural use of Action Observation Training (AOT) to enhance upper extremity function in persons with MS. Although past research has examined the effects of AOT in groups including stroke (Zhu et al., 2015) and Parkinson (Giorgi et al., 2018a) patients, as well as in lower extremity rehabilitation for persons with MS (Rocca et al., 2019a). While prior studies like Rocca et al. have demonstrated the utility of AOT for upper limbs in MS, our study expands on this work by employing an occupation-based intervention and using the comprehensive AMSQ and FSS to measure functional and fatigue-related outcomes. This innovative method addresses a gap in the literature and may provide fresh insights into the possible advantages of AOT for upper limb functionality in MS patients.

Method and materials

Participants

Inclusion criteria included:

• •A confirmed diagnosis of MS
• •Age between 18 and 63 years
• •Greater impairment on one side of the body
• •Impaired hand function and difficulty with activities of daily living (ADL)
• •A minimum score of 23 on the Mini-Mental State Examination (MMSE)
• •A score of at least 6 on the Expanded Disability Status Scale (EDSS)
• •Disease duration of less than 10 years
• •No history of other neurological disorders

Exclusion criteria included:

• •coexisting neurological disorders other than MS or any orthopedic injuries affecting the upper limbs
• •cognitive impairments such as apraxia that would interfere with participation
• •uncorrected severe visual or hearing impairments
• •an MS exacerbation during the intervention period
• •an inability to provide consistent attendance (defined as missing more than three treatment sessions).

People with MS referred to the Khuzestan MS Center were selected using the available sampling method.

Experimental design

This study was a non-randomized single-blind clinical trial conducted in the Neurology Clinic of Ahvaz University of Medical Sciences. A total of 52 individuals with MS were screened and assessed for eligibility from June 2024 to August 2024. Of these, 12 individuals were not included in the study due to failing to meet the inclusion criteria, and 10 individuals chose not to participate in the intervention. The 30 eligible s were assigned to their groups based on the order of enrollment; the first 15 individuals who provided consent were allocated to the intervention group, and the subsequent 15 were allocated to the control group. This non-randomized, consecutive assignment method was chosen for logistical feasibility (Fig. 1). It is important to note that the evaluators were blinded to the group allocation throughout the study.

Fig. 1.

Flowchart of Participant Screening, Enrollment, and Group Allocation in a Non-Randomized Clinical Trial Evaluating the Effects of Action Observation Training (AOT) Combined with Physical Therapy (PT) in Individuals with Multiple Sclerosis (MS).

Outcome measures

In this study, the AMSQ questionnaire was selected as the primary outcome measure, and fatigue, grip strength, and pinch strength were selected as secondary variables. A trained occupational therapist performed all clinical evaluations in a fixed order at baseline and after 4 weeks.

Arm function in multiple sclerosis questionnaire (AMSQ)

This 31-item questionnaire evaluates upper limb dysfunction in patients with MS. It uses a 6-point Likert scale, with scores ranging from 1, which means no restrictions, to 6, which means that the person is unable to perform the activity. A higher score indicates a greater impairment of hand function (Browne et al., 2014). The validity and reliability of this questionnaire were measured in Farsi, and Cronbach's alpha coefficient was reported to be 0.99 (Jameson et al., 2018).

Fatigue severity scale (FSS)

This questionnaire measures the intensity of fatigue in people with MS. This questionnaire has nine items and a 7-point Likert scale, which is graded from completely disagree to agree. A score higher than 36 in this questionnaire indicates that the person needs to be evaluated by a doctor for fatigue (Walton et al., 2020). This questionnaire is valid and reliable in the Farsi language, and it reported Cronbach's alpha coefficient as 0.96 and intraclass coefficient as 0.93, respectively, confirming its internal consistency and relative repeatability (Mirmosayyeb et al., 2022).

Dynamometer

In this study, the Jamar® Hydraulic Hand Dynamometer (Sammons Preston Inc., Bolingbrook, IL, USA) dynamometer was used to evaluate grip strength. It is considered the gold standard for measuring grip strength, due to its strong accuracy and reliability (Giorgi et al., 2018b). The evaluation method was that the participant sat on a chair without handles at a suitable height. The shoulder of the evaluated limb was in adduction (without any rotation), the elbow was at a 90-degree flexion, the forearm was in a mid-position, and the wrist was in a neutral position. The participant was asked to hold the dynamometer's handle vertically in line with the forearm and to press it with maximum force within a pain-free range. The assessment is done once with the affected hand and once with the non-affected hand, and taking into account a 60-second rest period, this is done three times for each hand. Then, the average of the three trials was recorded as the participant's maximum grip strength in pounds (lbs).

Pinch gauges

This study used a pinch gauge (Saehan SH5005 model) to evaluate the pinch strength. The evaluation method involved asking the participant to press the pinch gauge once with the affected hand and once with the non-affected hand, using the pad of the thumb and forefinger. After a 60-second rest period, the participant repeated the process three times for each hand. The average of the three trials was recorded as the participant's pinch strength in pounds-force (lbf).

Demographic information

Background information, including age, sex, body mass index, dominant hand, affected side, and duration of the disease, was collected through a questionnaire.

The study protocol was registered in Iran's clinical trial registry (IRCT20240302061148N1) and approved by the Clinical Research Ethics Committee of Jundishapur University of Ahvaz.

Intervention protocol

A panel of five experienced occupational therapists specializing in neurological rehabilitation selected the intervention tasks. The selection was based on a formal group consensus process, informed by clinical evidence and literature identifying common upper limb challenges in MS, such as impaired dexterity and fine motor control (Giorgi et al., 2018b, Çelik, 2018, Chen et al., 2007, Cordani et al., 2021b). These tasks, designed to be meaningful and occupation-based, were chosen to increase patient motivation and participation by simulating activities of daily living. The final selection was made during two structured sessions to ensure clinical relevance. These tasks were compiled into a 25-minute, 1080p video featuring 25 different upper limb functional activities, which are detailed in Table 1 and range from simple to complex movements.

Table 1.

Content of video.

Number of Repetitions	Type of Activity
10 rounds on each side	Winding a thread around a ball
3 times each	Opening and closing the lid of the worm box (large and small
10 times back and forth movements in the possible range	Dusting with a cloth
2 sets per hand	Thumb-to-Finger Opposition Tapping
1 time	Transferring a basket of balls onto a 4-step platform
1 time	Filling 5 glasses of water, placing it in the tray, and moving it to the top of 4 steps
1 time	Opening the bottle pouring water and drinking
5 times	Transfer the beans with a spoon to the container
10 times	Removing coins from the wallet
3 times	Open and close different screws
7 times	Transferring CDs to the above 4 steps
3 times	Opening and closing the lock
3 times	Open and close the small lock
2 times	Open the chocolate
1 time	Draw a pentagon and triangle pattern
5 times	Lifting a 4-kilogram flask up four steps
1 time	Write a 1-line sentence
1 time	Connect the numbers 1–10
5 times	Transferring a 3 kg bag from the floor to the top of the table (60 cm)
10 times	Turning the pages of a book
10 times	Return the cards
1 time	Cutting 3 different patterns from paper
3 times	Inserting and removing the key from the key fob
5 times	Cut therapy putty (green and blue color)
3 times	Stapling paper
1 time	Open the toothpaste and put it on the toothbrush
2 times	Tie shoes with laces

A healthy, right-handed individual was used to demonstrate the tasks, which were filmed from a first-person perspective. During individual sessions, each was seated on a suitable chair behind a table, facing a 15-inch laptop screen positioned 50 cm away. Patients were first instructed to attentively watch the video, which included upper limb tasks, written instructions, and repetition counts. After viewing, they were asked to imitate and perform the activities as demonstrated. Following each segment of the video and its corresponding imitation task, the therapist documented any errors or difficulties and provided corrective feedback to help the perform the activities accurately

Experimental group

In addition to routine physical therapy (12 sessions), the intervention group received Action Observation Training (AOT) exercises. AOT is grounded in the mirror neuron system, which activates during both action execution and observation (Cordani et al., 2021b), facilitating motor learning through visual input. Based on prior research and learning theories, AOT was administered for one month, three sessions per week (12 sessions total), each lasting one hour (Chen et al., 2007). Performance was considered successful when participants completed all parts of each task correctly. No time limit was imposed during the treatment sessions.

The following activities based on daily life were selected according to the muscles and movements most involved in MS disease, and their details are presented in Table 1.

Control group

The control group received routine physical therapy across 12 sessions, each lasting 45–60 min. These sessions primarily aimed to reduce pain and inflammation, rather than to strengthen the upper extremities. While some exercises may have involved the upper limbs, their primary purpose was pain management, not functional strengthening. Notably, no structured strengthening intervention targeting the upper limbs was provided to this group. The routine physical therapy followed national MS rehabilitation guidelines, including range-of-motion exercises, stretching, and pain management modalities, but excluded targeted strengthening of the upper limb. Since most patients in this group presented with upper limb pain, routine clinical care in similar settings typically emphasizes pain relief over strengthening. Therefore, modalities used in the control group reflect real-world rehabilitation practices for this population.

Statistical analysis

An independent analyst performed the data analysis using SPSS version 27. Data were presented as mean ± standard error (SE). Given the normal distribution of the post-intervention scores for AMSQ, average pinch strength, grip strength, and fatigue, Analysis of covariance (ANCOVA) was used to assess group differences while controlling for potential confounding variables. For each analysis, the baseline score of the respective outcome variable was used as the covariate. Effect sizes were also calculated to evaluate the magnitude of the observed effects and assess their practical significance. The significance level in all tests was set at p < 0.05.

Results

Baseline characteristics

Table 2 summarizes the baseline characteristics of individuals in both the intervention and control groups. No notable differences were detected between the two groups for sex distribution (p = 0.36), age (p = 0.78), years since diagnosis (p = 0.059), or BMI (p = 0.089). Hand dominance was primarily right-handed in both cohorts (14 right-handed and 1 left-handed per cohort, p = 1.00), and the distribution of the affected hand was analogous (8 right-hand affected vs. 7 left-hand affected in the control cohort; 8 right-hand affected vs. 7 left-hand affected in the intervention cohort, p = 1.00). The results demonstrate that the two groups were adequately comparable at baseline.

Table 2.

Baseline characteristics of the 2 study groups.

variable	control	intervention	P value
Sex (female/ male)	11/4	13/2	0.36
age	40.93	39.93	0.78
Years from diagnose	10.5	6.66	0.059
BMI	23.46	25.92	0.089
Dominant hand (right/ left)	14\1	14\1	1.00
Affected hand (right\left)	8\7	8/7	1.00

Primary outcome: AMSQ score

A notable disparity was detected in the Adjusted AMSQ Score between the intervention and control groups. Adjusted AMSQ scores were obtained using ANCOVA, with baseline AMSQ values entered as covariates to control for initial group differences. The mean adjusted score in the intervention group was 45.1 (SE = 3.2), significantly lower than that of the control group at 74.5 (SE = 3.2), with a mean difference of −29.5 (SE = 4.5, 95 % CI: −38.8 to −20.1, p < 0.05). The ANCOVA revealed a statistically significant group effect (F (Browne et al., 2014, Lamers et al., 2016b) = 42.10, p < 0.05, partial η² = 0.609), supporting a substantial intervention impact on upper limb function (Table 3). Levene’s test confirmed homogeneity of variances for all outcome variables except power grip strength of the unaffected hand (p = 0.001). Therefore, the results for this variable should be interpreted with caution.

Table 3.

ANCOVA results for adjusted post-test scores by group, including mean differences, standard errors, and 95 % confidence intervals.

Outcome	Group	Adjusted Mean	SE	95 % CI	p-value	Mean Difference (SE)	95 % CI (MD)
AMSQ	Intervention	45.10	3.20	[38.52, 51.68]	<0.001	−29.50 (4.50)	[−38.80, −20.10]
	Control	74.55	3.20	[67.97, 81.13]
Fatigue (FSS)	Intervention	35.94	2.80	[30.17, 41.71]	0.028	−9.60 (4.13)	[−18.07, −1.12]
	Control	45.53	2.80	[39.76, 51.30]
Power Grip (Affected) (lbs)	Intervention	48.67	2.26	[44.00, 53.34]	0.003	10.54 (3.20)	[3.98, 17.11]
	Control	38.13	2.26	[33.46, 42.80]
Power Grip (Unaffected) (lbs)	Intervention	58.28	1.69	[54.78, 61.78]	0.014	6.28 (2.39)	[1.36, 11.19]
	Control	52.01	1.69	[48.51, 55.51]
Pinch Grip (Affected) (lbs)	Intervention	4.63	0.31	[3.98, 5.28]	0.003	1.46 (0.45)	[0.55, 2.38]
	Control	3.17	0.31	[2.52, 3.82]
Pinch Grip (Unaffected) (lbs)	Intervention	5.24	0.25	[4.72, 5.76]	0.054	0.72 (0.36)	[−0.01, 1.46]
	Control	4.52	0.25	[4.00, 5.04]

Note. SE = Standard Error; MD = Mean Difference; CI = Confidence Interval. A p-value < 0.05 was considered statistically significant.

Secondary outcomes: grip and pinch strength

Power grip strength (affected and unaffected hands)

The power grip strength of the affected hand was significantly higher in the intervention group (M = 48.67 lbs, SE = 2.26) compared to the control group (M = 38.13 lbs, SE = 2.26), with a mean difference of 10.54 (SE = 3.20, 95 % CI: 3.98–17.11, p = 0.003).

The grip strength of the unaffected hand was also significantly greater in the intervention group (M = 58.28 lbs, SE = 1.69) versus the control group (M = 52.01 lbs, SE = 1.69), yielding a mean difference of 6.28 (SE = 2.39, 95 % CI: 1.36–11.19, p = 0.014). (Table 3).

Pinch grip strength (affected and unaffected hands)

For the affected hand, pinch grip strength was significantly higher in the intervention group (M = 4.63, SE = 0.31) than in the control group (M = 3.17, SE = 0.31), resulting in a mean difference of 1.46 (SE = 0.45, 95 % CI: 0.55–2.38, p = 0.003).

For the non-affected hand, the intervention group showed greater strength (M = 5.24, SE = 0.25) than the control group (M = 4.52, SE = 0.25), but this difference was marginally non-significant (MD = 0.72, SE = 0.36, 95 % CI: −0.01–1.46, p = 0.054). (Table 3).

Fatigue

Post-intervention, adjusted fatigue scores were significantly lower in the intervention group (M = 35.94, SE = 2.80) compared to the control group (M = 45.53, SE = 2.80), resulting in a mean difference of −9.60 (SE = 4.13, 95 % CI: −18.07 to −1.12, p = 0.028). ANCOVA confirmed a significant effect of group (F (Browne et al., 2014, Lamers et al., 2016b) = 5.40, p = 0.028, partial η² = 0.167), indicating that the intervention meaningfully reduced fatigue levels, where lower FSS scores signify improvement.

Discussion

This study examined the impact of AOT on hand functionality in individuals with MS. The results revealed a significant enhancement in the AMSQ score, signifying improved total hand function in the intervention group relative to the control group. Furthermore, the power grip strength in both the affected and unaffected hands shown a significant enhancement in the intervention group. Likewise, pinch gauge measurements in both hands exhibited enhancement subsequent to the intervention, and results indicate a significant reduction in fatigue following the intervention, with a strong effect size supporting its clinical relevance. Future studies should explore its long-term benefits. All observed changes were statistically significant (p < 0.05), indicating a substantial clinical effect of the intervention on manual dexterity and grip strength in individuals with multiple sclerosis.

The effectiveness of AOT in improving motor function has been thoroughly examined in several neurological disorders, especially in stroke recovery. A systematic review and meta-analysis of 7 randomized controlled studies including 276 stroke patients indicated that AOT had moderate to high effect sizes in enhancing arm and hand motor functions, ambulation, gait performance, and activities of daily living. These data highlight the efficacy of AOT as a significant intervention for motor rehabilitation following a stroke (Zhang et al., 2019).

There are other intensive therapies like Constraint-Induced Movement Therapy (CIMT), which has also been found to be a safe and effective technique for MS patients (de Sire et al., 2019). While CIMT focuses on constraining the less-affected limb to force the use of the more-affected one, it can be physically demanding and intensive. AOT provides a less physically demanding alternative that leverages a different neurological mechanism—the brain's mirror neuron system—and may be better tolerated by individuals with significant MS-related fatigue. Future research could directly compare the efficacy and patient tolerance of AOT versus CIMT in the MS population (de Sire et al., 2019).

Research on AOT in the setting of MS is currently restricted, although it has promise. Rooca et al. conducted a pilot experiment with 41 MS patients with dominant-hand motor impairment to assess the effects of a 10-day AOT regimen. The findings demonstrated substantial enhancements in right upper limb functionality following the operation, along with structural and functional alterations in the action observation network. The neuroplastic alterations were positively associated with the noted motor enhancements, indicating that AOT promotes motor function recovery in MS via central nervous system reconfiguration (Rocca et al., 2019b). Shamili et al. conducted a randomized controlled experiment to assess the impact of AOT on upper extremity function in 24 individuals with chronic stroke. The study demonstrated substantial enhancements in occupational performance and satisfaction within the experimental group, although traditional motor tests exhibited no significant disparities between the groups. Furthermore, alterations in corticospinal excitability were noted, especially in the abductor pollicis brevis muscle. The findings indicate that AOT improves motor recovery via neurophysiological changes, underscoring its promise as a rehabilitation method. Nonetheless, its use in multiple sclerosis has yet to be investigated, underscoring the necessity for more research into its effectiveness for upper limb rehabilitation in this demographic (Shamili et al., 2022). Supporting previous findings, our results indicate that a 4-week AOT treatment markedly improves hand function, grip strength, and pinch strength in patients with MS. This study significantly contributes to the current literature by using a single-blind, controlled design and using the AMSQ as the major outcome measure, offering a full evaluation of upper limb functioning.

The improvement in AMSQ scores and hand function metrics in the intervention group can be attributed to several underlying causes. A primary process is neuroplasticity, which refers to the brain's ability to remodel by forming new neural connections in response to therapy and training (Nahum et al., 2013, Joshua, 2022). Repetitive motor training, particularly in individuals with MS, has been shown to elicit anatomical and functional modifications in the sensorimotor cortex, thereby improving motor control and coordination (Bonzano et al., 2019, Florio, 2025, Liu et al., 2024). A crucial process is the activation and adaptation of muscle strength (Zhang et al., 2019). Focused grip and pinch workouts enhance neuromuscular efficiency, improving motor unit recruitment and synchronization, which results in improved power grip and pinch force (Xiao et al., 2024, Herring-Marler TL, 2011). In multiple sclerosis patients, muscular weakness frequently arises from compromised corticospinal conduction, yet systematic therapies can enhance motor unit firing rates and muscle endurance, mitigating functional deterioration (Moumdjian, 2013, Brown, 2024).

Furthermore, the alleviation of MS-related fatigue may have facilitated functional improvements (Zielińska-Nowak et al., 2020). Fatigue is a significant constraint in multiple sclerosis, impairing muscular function and coordination (Zielińska-Nowak et al., 2020). Targeted therapies may reduce perceived exertion, improve energy efficiency, and enhance endurance, allowing patients to excel in grip and pinch activities. These processes collectively enhance the positive impact of our intervention on AMSQ scores and hand function, underscoring the importance of organized motor therapy in managing MS.

A principal strength of this study lies in its meticulous design, which encompasses suitable group matching for baseline characteristics and the application of standardized evaluation instruments for hand function. Moreover, the intervention was customized exclusively for MS patients, guaranteeing its pertinence and usefulness. The study is enhanced by its objective outcome measurements, hence minimizing the potential for subjective bias in assessing hand function.

The findings of this study highlight the potential of AOT as a valuable addition to rehabilitation programs for individuals with MS. Given the significant improvements observed in grip strength, pinch force, and overall hand function, integrating AOT into standard neurorehabilitation protocols could enhance motor recovery and functional independence in MS patients. The non-invasive nature of AOT makes it a practical and accessible intervention, particularly for individuals with mobility limitations. Future research should explore how AOT can be optimized—whether through personalized task selection, extended training durations, or integration with other neurorehabilitation strategies such as virtual reality and brain stimulation techniques. Additionally, large-scale clinical trials with long-term follow-up are necessary to determine the durability of these functional gains and to establish standardized guidelines for incorporating AOT into clinical practice.

This study has several important limitations that must be acknowledged. First, the non-randomized design introduces a risk of selection bias and prevents definitive causal conclusions. Second, the relatively small sample size (n = 30) limits statistical power and the generalizability of the findings to the wider MS population. Third, the investigation assesses only short-term outcomes, and the 4-week follow-up means we cannot comment on the long-term durability of the observed benefits. Fourth, this study did not stratify participants by disease severity, which may influence intervention outcomes. Finally, the control group's focus on pain management rather than strengthening creates an imperfect comparison. Therefore, these findings should be considered preliminary and require validation in larger, more rigorous randomized controlled trials.

Conclusion

This study presents persuasive evidence that AOT, when included into typical rehabilitation regimens, markedly improves upper limb functioning in persons with MS. The intervention resulted in significant enhancements in AMSQ scores, grip strength, and pinch force, probably attributable to processes including activation of the mirror neuron system, increased motor unit recruitment, and less MS-related fatigue. Notwithstanding several limitations, such as a limited sample size and absence of long-term follow-up, our findings substantiate the therapeutic significance of AOT as a non-invasive and efficacious method for enhancing motor recovery and functional autonomy in MS patients. Subsequent research should investigate its enduring advantages and amalgamation with other neurorehabilitation methodologies to enhance patient results.

CRediT authorship contribution statement

Mahsa Fadavighaffari: Writing – original draft, Supervision. Meimanat Akbari: Writing – review & editing, Investigation. Sara Khosravi: Writing – original draft, Methodology. Akram Ansari: Writing – original draft, Supervision, Investigation. Fatemeh Savaedi: Writing – original draft, Conceptualization. Fatemeh chichagi: Writing – original draft, Methodology. Eftekhar Azarm: Writing – original draft, Supervision. Omid Anbiyaee: Writing – original draft. Nazanin Moeini: Formal analysis.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Funding

None.

Declaration of Competing Interest

The authors declare that they have no competing interests

Data availability

The datasets generated and analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.