Introduction
Carpal tunnel syndrome (CTS) is a mononeuropathy resulting from the compression of the median nerve within the confined space of the wrist bones and transverse carpal ligament [1, 2]. CTS is a costly complication that significantly diminishes an individual’s quality of life [3]. Accounting for 90% of neuropathy complications, this syndrome has various symptoms, such as numbness, tingling in the hand, hand and wrist pain, and muscle dysfunction [4]. These sensory and motor impairments can disrupt various daily activities, such as buttoning clothes, holding a book while reading, or handling a phone [5]. Females aged 40 to 60 years are more susceptible to CTS compared to males, primarily due to having a smaller carpal tunnel [2, 6].
The treatment of CTS is typically categorized into surgical and conservative approaches. Surgical intervention is recommended for severe cases, while conservative treatments are suggested for mild to moderate instances [7]. Common conservative treatments include various anti-inflammatory medications, orthoses, transcutaneous electrical nerve stimulation, low-level laser therapy, ultrasound, shockwave therapy, magnet therapy, iontophoresis, manipulation, mobilization, and specific exercises [8, 9].
Although previous studies have shown the positive impact of physiotherapy treatment programs in alleviating pain and improving symptoms among patients with CTS, the effects of two distinct types of therapeutic exercises, namely tendon glide and nerve glide, on both valid and reliable subjective and objective outcomes measures, including visual analog scale (VAS) and Boston questionnaire, electrodiagnostic test parameters and functional measures have yet to be explored. Among the spectrum of available therapeutic modalities, according to studies, the efficacy and effectiveness of therapeutic exercise in CTS have been demonstrated [10]. Furthermore, the specific effects of nerve and tendon gliding exercises have been investigated and compared together in limited studies [8, 11-13]. Some of these studies lack a standardized protocol, blinding and appropriate control group, or have not utilized valid and practical outcome measures or gold standard assessments. Additionally, they have not included home exercises or follow-up for investigating long-term sustainability of the result. Accordingly, considering the existing research gaps, examining these two therapeutic exercise methods under a standard and comprehensive protocol could help clarify the actual effects of these two common treatment approaches.
To the best of our knowledge, this is the first study to compare the effects of nerve glide and tendon glide using a standardized protocol, including home exercises and follow-up, to assess the long-term sustainability of treatment effects with valid objective and subjective outcome measures.

Materials and Methods
Study design
Following the approval of the research proposal at the University of Social Welfare and Rehabilitation Sciences and obtaining ethical clearance from the university’s Ethics Committee, we were authorized to conduct the research project at the Rofeydeh Hospital, Iran. During in-person visits to the hospital in 2023, the participants were diagnosed with CTS by neurology or physiatrist specialists.
If the patients met the inclusion criteria, they would sign an informed consent form. Before starting the treatment, the patients completed demographic data and Boston questionnaires. Pain levels were measured using VAS [14, 15]. Meanwhile, hand grip strength was measured by a dynamometer [16, 17]. Furthermore, sensory and motor latency, nerve conduction velocity, and amplitude using electrodiagnostic tests will be assessed by a physician [18, 19]. 
Following the completion of the initial phase, the first group underwent the treatment with ultrasound therapy and nerve glide exercises, while the second group received ultrasound therapy combined with tendon glide exercises. The sample allocation process was executed through a random lottery mechanism by concealed envelope allocation, conducted by a blinded examiner. The research was carried out at the rehabilitation clinic located within Rofeydeh Hospital, Iran. 

Sample size
According to the article by Brininger et al. [20], the standard deviation (SD) of symptom severity scale scores was determined for two groups as SD1=0.8 and SD2=0.9, respectively. The mean difference between the two groups was d=0.7. Considering the power of 80% (z=0.85) and a confidence level of 95% (z=1.96), the sample size for each group was calculated at 23, resulting in a total sample size of 46 individuals (Equation 1).


This study included individuals with a confirmed diagnosis of CTS based on the following inclusion and exclusion criteria.

Inclusion and exclusion criteria
The inclusion criteria were participants within the age range of 30 to 75 years, including both males and females; individuals diagnosed with CTS by a neurologist or physiatrist through clinical and electrodiagnostic tests; participants who had a positive Fallon and Tinel test [21, 22]. Meanwhile, the exclusion criteria were participants who had previously undergone carpal tunnel surgery; participants who had received corticosteroid injections within the last 6 months or any other treatment within the last 3 months; participants presenting with other neuromuscular problems; participants with immune system defects; pregnant women; and individuals with psychosocial problems.
All eligible patients who were willing to participate in the study formally signed an informed consent form. The participants experiencing an increase in pain during the study were not included [23]. Individuals expressing a desire to withdraw from the study at any stage were excluded [23]. This study has obtained approval from the Medical Ethical Review Board of the University of Social Welfare and Rehabilitation Sciences.

Data collection
The first group initiated their treatment, which consisted of two sessions per week for 8 weeks [11, 24, 25]. The treatment involved the use of ultrasound (215p NOVIN medical engineering company; 0.8 W/cm², 1 MHz, 1:4) for 15 min on the site of the median nerve entrapment beneath the transverse carpal ligament (Figure 1) [26], along with nerve glide exercises. In these exercises, the patients were instructed to be in a seated position, ensuring relaxation of their proximal muscles, as their capabilities in performing exercises may vary with different arm positions. These exercises included six positions that are described as follows according to Kisner’s therapeutic exercises textbook [27]: 
1) In the first position, the wrist is maintained in a neutral posture while flexing the thumb and fingers; 2) The second position involves extending the fingers while keeping the thumb in a neutral position; 3) In the third position, both the wrist and fingers are extended, while the thumb remains in a neutral position; 4) For the fourth position, the wrist, fingers and thumb are all in the extended position. 5) The fifth position is a continuation of the fourth, where the forearm is moved into supination; 6) Similar to the fifth position, in the sixth position, the other hand gently stretches the thumb while maintaining the extended positions of the fingers, wrist, and supinated forearm [24]. Each position will be held for 5 s. [12] and the exercises will be repeated ten times in each session, three times a day, over 8 weeks (Figure 2).  The next group’s interventions involved ultrasound and tendon glide exercises. These exercises involve placing the hand in five different positions (Figure 3): 1) Neutral: All finger joints are in a neutral position; 2) Hook: The metacarpophalangeal joints are in extension, while the interphalangeal joints are in full flexion; 3) Full fist: All finger joints are in full flexion; 4) Tabletop: The metacarpophalangeal joint is in a 90-degree flexion position while the interphalangeal joints are in a neutral position; 5) Straight fist: The metacarpophalangeal and interphalangeal joints are in flexion, while the distal interphalangeal joint is in extension.
The exercises were repeated in the same manner as the first group. After completing the treatment, all tests and assessments were repeated in the final session [17, 28]. 
Additionally, the patients were instructed to perform these exercises at home, while the participants were monitored by the researcher through phone and video calls. A phone call or video call was made once a day. Three months after completing the study, participants underwent re-testing, and the long-term effects of the interventions were evaluated.

Outcome measures
To assess the severity of symptoms before and after treatment, various subjective, objective, and functional methods were employed. The assessments included VAS, the Boston questionnaire, dynamometer measurements, and electrodiagnostic tests.
The Boston questionnaire was designed to evaluate the symptoms and functional status of patients with CTS. It consists of two sections, namely the symptom severity scale with 11 questions to assess CTS symptoms and the functional status scale with 8 activities reflecting daily tasks, each question in both subscales, scored from 1 to 5 [29].
Grip strength can be measured by using a dynamometer (SH5000-3 Hydraulic Hand Evaluation Kit, 3pcs). To do that, we adjust it to the index finger’s second joint, ensure it reads 0.0 kg/lbs., stand upright, hold it by one’s side, squeeze for 4-5 s then relax, repeat twice per hand, record the highest reading, and sum for total score (Figure 4) [17]. The patients rated their pain using VAS, assigning a score from 0 (no pain) to 10 (the most severe imaginable pain) [30].
For definitive diagnosis and determining the severity of CTS, electrodiagnostic tests were employed. These tests involve stimulating the median nerve and recording sensory and motor responses to measure nerve response delay, conduction velocity, and amplitude [31, 32].

Patient flow
This randomized clinical trial had an inclusion period of 12 months and a follow-up of 3 months. The patient recruitment started in January 2023 and ended in December 2023. 

Data analysis
For data analysis, IBM SPSS software, version 27 was utilized. The following statistical tests were employed to compare the two groups and assess pre and post-treatment comparisons: Independent sample t-test for comparing means between two independent groups; Mann-Whitney U tests when data distribution was not normal for comparing two independent groups; analysis of covariance for assessing the effectiveness of interventions and comparing them, considering the baseline differences. These statistical analyses are designed to provide in-depth insights into the comparisons and treatment effects observed in the study.

Results
Despite the number of studies conducted on the effects of therapeutic exercises in CTS, the results are contradictory, sometimes due to the lack of a standardized protocol, the absence of blinded evaluators or patients, and the lack of standardized outcome measures and follow-up visits. Some of these studies have limitations, including the following items.
Small sample size: Some studies included a small number of participants, which may limit the applicability of the findings to a broader context [33-36].
Lack of control group: In certain studies, the absence of a control group makes it difficult to assess the true effectiveness of therapeutic exercise compared to other interventions or no treatment [37].
Variability in exercise protocols: The exercise programs used in different studies varied in terms of duration, frequency, and types of exercises, making it challenging to compare the results and draw definitive conclusions [38].
Inconsistency and low validity and reliability of outcome measures: The use of different outcome measures in various studies makes it difficult to compare and synthesize the results [12, 24]. Electromyographic tests, due to their cost and the need for specialist administration, are infrequently used in studies [11, 36, 39].
Lack of blinding: In some studies, the assessors or patients were not blinded to the intervention, which may introduce bias in the evaluation of treatment outcomes [24].
Short follow-up duration or no follow-up: Some studies had a relatively short follow-up period, which may underestimate the long-term effects of therapeutic exercise in CTS [12, 20].
Considering these limitations, further well-designed studies with larger sample sizes, standardized protocols, blinded assessments, and robust outcome measures are needed to better understand the effects of therapeutic exercise in the CTS.

Discussion
Most studies have shown that the therapeutic effects of nerve- glide, and tendon-glide exercises are more significant than other non-invasive treatments [38], In a study by Alam et al. (2018), nerve mobilization therapy showed greater effectiveness in reducing pain and functional limitations compared to ultrasound in patients with CTS [37]. The confirmation of these effects, even in comparison with pharmaceutical treatment has the greater significance and effectiveness of these methods [40-42], In a study by Mohamed et al., median nerve mobilization showed a significant advantage over drug therapy for 28 individuals with CTS, based on Tinel and Phalen tests, the Boston questionnaire, and electroneurodiagnostic tests over six weeks [40]. In another study, Bartkowiak et al. compared ultrasound and low-level laser therapy combined with tendon and nerve gliding in seventy participants. Both groups showed improvement in VAS, Phalen, Tinel tests, dynamometry, and the Boston questionnaire but they did not have gold standard electrodiagnostic tests [24]. In a study conducted by Abdolrazaghi et al. the effect of 6 weeks of nerve glide and tendon glide exercises on the treatment of patients with CTS was investigated by the Boston questionnaire. In this study, no significant difference was observed in the experimental group who were using a splint [12]. The study’s reliability depends on participant count and a control group, Meanwhile, in a 2020 study by Kurniawti et al., nerve mobilization and kinesiotaping improved VAS scores in 20 participants with CTS without a control group and gold standard assessment [34].
One similar study to our study was conducted by Horng et al. who studied the effects of tendon and nerve glide exercises on CTS. In this study, 60 participants were divided into three groups as follows: Tendon gliding with paraffin therapy and splint, nerve mobilization with paraffin therapy and splint and a group with paraffin therapy and splint. The Boston questionnaire and nerve conduction velocity were taken from the patients before and after treatment. the results showed that tendon gliding is more effective than nerve mobilization in improving CTS [11]. While we examine additional outcome measures, particularly functional objective tests in addition to subjective and electrodiagnostic ones, implementing double blinding with a larger sample size and incorporating follow-up visits will enhance our study’s power. This approach will allow us to speak with greater certainty about the study results, especially given the controversy among similar studies.

Conclusion
This project can lead to more definitive clinical decisions regarding more effective treatments for patients with carpal tunnel syndrome, while saving time and costs. 

Study limitations
In the present study, due to the limited time for sampling and the time-consuming nature of the sampling process, as well as the need to adhere to ethical considerations in providing fair treatment, a control group (without therapeutic exercise intervention) was omitted. Another limitation was the inability to examine and compare patients with three different severities of CTS, including mild, moderate and severe, in terms of their response to treatment. Therefore, in future research, it is recommended to consider these limitations and address them.

Ethical Considerations
Compliance with ethical guidelines
All eligible patients who were willing to participate in the study formally signed an informed consent form. This study has obtained approval from the Medical Ethical Review Board of the University of Social Welfare and Rehabilitation Sciences, Tehran, Iran (Code: IR.USWR.REC.1402.171).

Funding
The present article was extracted from the PhD thesis of the Azadeh fasaie, approved by Department of physiotherapy, Faculty of rehabilitation, University of social welfare and rehabilitation sciences.

Authors' contributions
Conceptualization: All authors; Methodology: Azadeh Fassaii, Somayeh Mohamadi, and Samaneh Hossein Zadeh; Resources: Azadeh Fassaii and Somayeh Mohamadi; Software: Mosleheddin Adibhesami; Validation: Azadeh Fassaii; Investigation: Somayeh Mohamadi; Data curation: Azadeh Fassaii and Samaneh Hossein Zadeh; Formal analysis: Azadeh Fassaii, Samaneh Hossein Zadeh, and Mosleheddin Adibhesami; Writing the original draft: Azadeh Fassaii; Review and editing: Somayeh Mohamadi; Visualization: Azadeh Fassaii, Supervision: Somayeh Mohamadi; Project administration: Azadeh Fassaii, Somayeh Mohamadi and Mosleheddin Adibhesami. 

Conflict of interest
The authors declared no conflict of interest. 



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