Telerehabilitation for Neurological Motor Impairment: A Systematic Review and Meta-Analysis on Quality of Life, Satisfaction, and Acceptance in Stroke, Multiple Sclerosis, and Parkinson’s Disease

Telerehabilitation (TR) seems to be a viable and feasible solution to face the rehabilitative challenges posed by neurological impairments and to improve patients’ quality of life (QoL). This review aims to synthesize and analyze the evidence on the impact of physiotherapy intervention through TR on QoL in patients with stroke, Parkinson’s disease (PD), and multiple sclerosis (MS), together with an evaluation of their satisfaction and technology acceptance levels. Through a systematic search of the literature and a screening process, treatment effects were assessed with meta-analyses using the standardized mean difference, setting the confidence interval at 95%. We included 28 studies in the review, which were analyzed for methodological quality, whereas 16 studies were included in the meta-analyses. The results suggest a significant improvement in QoL in patients who underwent TR. We were unable to perform analyses for satisfaction and technology acceptance outcomes due to insufficient data. Overall, motor TR has a positive impact on the QoL of patients with neurological diseases, especially in stroke patients; although caution is needed in the interpretation of the results due to the high heterogeneity found. For PD and MS, TR seems to yield comparable results to in-person treatment.


Introduction 1.Description of the Conditions
Neurological motor impairments resulting from stroke, multiple sclerosis (MS), and Parkinson's disease (PD) pose significant challenges to affected individuals and to healthcare systems.Stroke, a leading cause of adult disability globally, is often associated with partial or complete paralysis on one side of the body [1].MS, characterized by the demyelination of nerve fibers, results in a wide range of motor impairments, including muscle weakness, spasticity, and ataxia [2,3].PD, primarily known for its motor symptoms such as tremors, rigidity, and bradykinesia, significantly impacts an individual's ability to perform everyday tasks [4].All these conditions have in common the long-term consequences the disease brings with it, resulting in chronic impairments that require long-term multidisciplinary management.However, healthcare systems are still struggling to answer to the rehabilitative needs of people with neurological impairments.In addition to this, neurological diseases have a major impact not only on the different functions of affected individuals (e.g., motor, speech, language, cognitive impairments), but also on their quality of life (QoL) [3,5,6].Indeed, while it is known that there is an issue for healthcare systems in providing a certain continuity of care for individuals with neurological conditions at an adequate dose [7], the perceived QoL levels of individuals with stroke, PD, and MS seem to decrease drastically [3,5,6].

Description of the Intervention
Telerehabilitation (TR), a dynamic and evolving branch of telemedicine, has emerged as a promising approach to provide comprehensive rehabilitation services remotely [8].By using technological advancements, TR is uniquely positioned to address the different impairments associated with these neurological conditions, offering a wide range of therapeutic exercises, educational resources, and emotional support in patients' own homes, by providing synchronous (i.e., online, with the presence of the therapist in real time) and asynchronous (i.e., by monitoring patients' training) treatments [9].The possibility for the patient to have treatment at home in a synchronous or asynchronous modality therefore has positive effects not only in terms of the dose of treatment that can be delivered and the possibility to continue the rehabilitation program at home, but also in terms of QoL, which in turn could have positive effects on functional improvements.Indeed, treatment conducted within patients' social, educational, and vocational environments can lead to improved functional outcomes and enhanced family and community integration [10].Emerging evidence suggests that TR may hold promise as an effective alternative to conventional treatment for various neurological disorders.TR has been shown to be as effective as conventional rehabilitation for motor, cortical, and mood disorders in stroke survivors [7,[11][12][13].Additionally, non-immersive virtual reality (VR)-based TR is a promising approach for improving static and dynamic balance and gait in people with PD and MS [14][15][16].Likewise, TR may be beneficial for prolonging and maintaining the goals achieved during rehabilitation [12].

Why It Is Important to Conduct This Review
Despite the growing interest in TR, there remains a critical gap in the literature regarding its comprehensive impact on the QoL, satisfaction, and acceptance among individuals affected by stroke, MS, and PD.The focus on these aspects is crucial, given the multifaceted nature of these neurological conditions and the different impairments they encompass.Understanding how TR can improve QoL, increase patient satisfaction with the treatment process, and enhance the acceptance of these novel approaches is essential for ensuring comprehensive and effective care for individuals grappling with the complex challenges posed by these neurological conditions.This review contributes to the enhancement of knowledge regarding TR and its impact on QoL in neurological conditions.Its implications serve as a useful resource for researchers, clinicians, and healthcare providers, offering insights that contribute to the ongoing efforts to enhance the well-being of individuals dealing with complex neurological challenges.

Objectives
This systematic review and meta-analysis aim to synthesize and analyze existing evidence on the role of motor TR in improving QoL levels, together with the investigation of the satisfaction and acceptance levels in patients with neurological impairments (i.e., stroke, MS, PD) who underwent TR.

Materials and Methods
This systematic review with a meta-analysis was conducted according to the PRISMA guidelines [17], and the protocol was registered a priori in the PROSPERO database under the following registration number: CRD42021276763.

Electronic Searches
We conducted a comprehensive search for articles written in English in PubMed, Embase, Web of Science, and the Cochrane Library.We included studies without time restrictions, with the last search conducted on 24 October 2022.A detailed description of the search strategy is presented in Appendix A.

Study Selection
In this review, we planned to include (1) studies designed as randomized controlled trials (RCT), quasi-randomized controlled trials (quasi-RCTs), and controlled clinical studies (CCTs), with (2) adults (>18 years) diagnosed with stroke, PD, and MS, undergoing (3) physiotherapy interventions based on TR (e.g., home-based rehabilitation conducted via TR, including interventions delivered through computers, virtual reality, and video conferencing) as compared to (4) conventional therapies (e.g., exercises, mobilizations).Eventually, (5) the primary outcome of interest was the assessment of QoL.Secondary outcomes included levels of patient satisfaction and technology acceptance.We excluded studies with healthy individuals or with subjects affected by other neurological or neurodegenerative pathologies and those not involving physiotherapy TR interventions.Furthermore, studies not comparing TR intervention to conventional therapies and not assessing QoL, satisfaction levels, or acceptance of TR technology were excluded.For study selection through abstract screening after duplicates' removal, two independent reviewers conducted the screening of the records, based on titles and abstracts, using the Rayyan tool [18].A third reviewer was selected to solve any disagreements.At the end of this process, full texts of the records were obtained, and the same procedure was used for full text screening and for the assessment of the methodological quality of the studies (i.e., risk of bias assessment).

Outcomes
The primary outcome of this review was the QoL, as defined by the World Health Organization (WHO) as the multidimensional perception of an individual's state of physical, mental, and social well-being within their personal, cultural context and in relation to the values upon which they base their goals, expectations, standards, and concerns [19].This definition denotes an ideal state, with a concept that requires the construction of indicators capable of capturing the many subjective and functional dimensions of wellbeing.Outcome measures considered consisted of questionnaires related to QoL for the different pathologies included in the review (e.g., stroke impact scale [SIS] for stroke, Parkinson's disease questionnaire-8 [PDQ-8] for PD, multiple sclerosis quality of life 54 [MSQOL-54] for MS).Satisfaction levels and technological acceptance of TR systems were evaluated as secondary outcomes, assessed with specific questionnaires (e.g., stroke-specific patient satisfaction with care [SSPSC], client satisfaction questionnaire [CSQ]).

Data Extraction and Management
A specific synoptic table was created and filled with data extracted from the included studies.The following study details were extracted: 1. Citation details: authors, year of publication; 2. Aim of the study; 3. Study type; 4. Participant details (e.g., diagnosis, age, gender distribution, disease severity, months/years since the event, number of patients per group); 5. Intervention (i.e., type and dose); 6. TR method (e.g., hardware, software, and type of connection, delivery mode); 7. Assessment time points; 8. Outcome measures (related to our study objectives: QoL, satisfaction, and acceptance); 9. Conclusions of the studies.

Assessment of Risk of Bias in Included Studies
The included articles were qualitatively analyzed by two independent reviewers using the Revised Cochrane Tool Risk of Bias 2 (RoB2) [20] and the Cochrane Tool Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) [21].A third reviewer solved any disagreements.Through RoB2, we assessed the following domains: (1) selection bias, encompassing sequence generation and allocation concealment; (2) detection bias, examining the blinding of outcome assessment; (3) attrition bias, addressing incomplete outcome data; and (4) reporting bias, focusing on selective reporting.Each domain's risk of bias was coded as 'high risk' in the presence of a significant likelihood of bias, 'low risk' in cases with a low probability of bias, and 'unclear risk' when a precise determination of bias incidence was uncertain.For non-randomized studies, we used ROBINS-I, with which we evaluated the following coded biases: confounding bias, participant selection, intervention classification, deviations from intended interventions, missing data, measurement of outcomes, and selection of reported results.Each domain was judged with a "low risk", "moderate risk", "serious risk", or "critical risk" of bias.The overall risk of bias for each study was then summarized by considering judgments across all domains.

Measures of Treatment Effect
We used Review Manager 5.4 (RevMan 2020) [22] to conduct the review and to perform statistical analyses.Given the varied measurement scales of outcomes, treatment effects were assessed using the standardized mean difference (SMD).The confidence interval (CI) for continuous outcomes was set at 95%.For satisfaction and technological acceptance outcomes, quantitative results could not be obtained due to the nature of their data; hence, they are described in a narrative manner.

Dealing with Missing Data
In the presence of missing data or data not reported as means and standard deviations, we contacted trial authors to ask for them (e.g., information and/or data reported as means and standard deviations to carry out the meta-analyses).Whenever feasible, we converted available data using the procedures outlined in Section 6.5.2.2 of the Cochrane Handbook for Systematic Reviews of Interventions [23].If we did not receive a response and we were not able to extract this kind of data, the article was included in the review but excluded from the meta-analysis.

Subgroup Analysis and Investigation of Heterogeneity
We planned to perform subgroup analysis according to neurological diseases (i.e., stroke, PD, MS).Statistical heterogeneity was assessed with the I 2 statistic, establishing the cut-off value at 50%.

Data Synthesis
We conducted meta-analyses based on a random-effects model, based on the presence of heterogeneity, with 95% CI using RevMan 5.4.We explored heterogeneity as detailed above.

Results of the Search
The database search yielded a total of 1092 results from four electronic databases.After removing duplicates, 963 abstracts were screened using the Rayyan tool.Subsequently, 36 studies were included for full-text screening.After full-text screening, 28 studies met the inclusion criteria for qualitative analysis.At the end of the process, 16 studies were included for quantitative analysis.The PRISMA flowchart of the review process is shown in Figure 1.

Results of the Search
The database search yielded a total of 1092 results from four electronic databases.After removing duplicates, 963 abstracts were screened using the Rayyan tool.Subsequently, 36 studies were included for full-text screening.After full-text screening, 28 studies met the inclusion criteria for qualitative analysis.At the end of the process, 16 studies were included for quantitative analysis.The PRISMA flowchart of the review process is shown in Figure 1.

Excluded Studies
After full-text screening, we excluded a total of eight studies.Two studies [52,53] were considered ineligible due to their non-experimental nature, whereas another five studies [54][55][56][57][58] were excluded as they did not involve any physiotherapy or motor treatments but solely focused on tele-visits.One study [59] was excluded because it included patients with stroke, as well as patients with severe acquired brain injuries and traumatic brain injuries, without providing a separate analysis of their results.

Risk of Bias in Included Studies
The 26 randomized clinical trials were analyzed using the RoB2 tool, and the synthesis of the results is graphically presented in Figure 2; the remaining 2 non-randomized trials were analyzed using the ROBINS-I tool, and the detailed description of the evaluation is presented in Table 1.In addition, in one study [26], the experimental group was statistically more active at the baseline; in three studies  received a low risk of bias while the other 9 raised some concerns.These concerns primarily stemmed from the lack of information regarding participant allocation blinding during the randomization phase.In addition, in one study [26], the experimental group was statistically more active at the baseline; in three studies [27,41,47], some information regarding how the randomization process was conducted was missing.Baseline data for the participants were missing in one study [27] and in two [33,40] the randomization process was adjusted to balance the two groups or to follow the personal preferences of the participants.-Bias due to deviations from intended interventions: In 16 studies, the domain received a low risk-of-bias rating.Two studies [31,49] raised some concerns among reviewers, and eight studies received a high risk-of-bias rating due to the exclusion of some data from the final analysis for a high number of patients who did not complete the study [24,27,30,33,41,[45][46][47].-Bias due to missing outcome data: Twenty-one studies received a low risk-of-bias rating.Five studies received a high risk-of-bias rating [24,30,[45][46][47].The reason for this rating was the same as for the previous domain.-Bias in measurement of the outcome: All studies in this domain received a low risk-ofbias judgement.-Bias in selection of the reported result: Twelve studies received a low risk-of-bias judgment.Ten studies raised some concerns, and four studies received a high risk-ofbias judgment.Seven studies modified data from the protocol, introducing variations in assessment scales, outcomes, and the expected timepoints for evaluations.These modifications led to a high risk-of-bias judgment in four studies [28,29,33,36], and raised concerns in two studies [30,31].

Risk of Bias in Non-Randomized Studies
The study performed by Benvenuti et al. [25] was judged with a critical risk of bias due to the pooling of the two groups and subsequent data combination after trial completion.Additionally, there was a substantial 26.5% overall data loss, and no statistical method was used to analyze the data of participants who did not complete the study.The study conducted by Isernia et al. [50] was judged to have a serious risk of bias due to the unbalanced nature of the two groups from the outset (3:1), and the restriction of the first assessment analysis to the experimental group only.The results of individual studies were reported as they could not be combined due to pathology heterogeneity (Figure 4).

Narrative Synthesis
Acceptance and satisfaction levels of the technology were primarily assessed through a variety of measurements, predominantly qualitative in nature, rendering quantitative

Narrative Synthesis
Acceptance and satisfaction levels of the technology were primarily assessed through a variety of measurements, predominantly qualitative in nature, rendering quantitative analyses unfeasible.TR emerged as a viable and well-accepted approach, demonstrating a satisfaction level comparable to that of conventional treatments.These outcomes were

Narrative Synthesis
Acceptance and satisfaction levels of the technology were primarily assessed through a variety of measurements, predominantly qualitative in nature, rendering quantitative analyses unfeasible.TR emerged as a viable and well-accepted approach, demonstrating a satisfaction level comparable to that of conventional treatments.These outcomes were analysed through various measurements, mostly qualitative, and therefore, quantitative analyses were not feasible.Table A1 (Appendix B) provides the summary of the overall 17 included studies that measured these outcomes along with their respective results.

Effects of Telerehabilitation Compared to Conventional Treatment for Improving Patients' Satisfaction
In the narrative synthesis of studies investigating satisfaction associated with TR use, a total of 13 studies have been included.To assess satisfaction, mainly ad hoc questionnaires [27,30,31,34,40,43,47,49] or personalized and modified versions of existing models [29] were used, as well as official assessment scales [38].Additionally, structured interviews [25] and surveys [26,36] were conducted.

Effects of Telerehabilitation Compared to Conventional Treatment for Acceptance
A total of eight studies measured technological acceptance.For the assessment of acceptance, official questionnaires [25,42] and semi-structured telephone interviews [44] were employed.Additionally, it was evaluated through ad hoc questionnaire, and, in one study, it was inferred from the actual number of treatment hours [24].

Discussion
With this review with meta-analyses, we aimed to synthesise and analyse the current evidence on the impact of motor TR on QoL levels in neurological diseses (i.e., stroke, MS, and PD), together with an evaluation of acceptance levels and satisfaction with the technology.
Our meta-analysis indicates that motor TR has a significant and overall positive effect on QoL in patients with neurological diseases with a moderate level of heterogeneity (I 2 = 48%) across studies.Within the stroke subgroup, the overall effectiveness of TR is notably significant, pointing to a substantial impact on improving QoL.However, the high heterogeneity (I 2 = 68%) suggests that there is a considerable variability among the studies in this subgroup.This variability may be attributed to differences in interventions, treatment dosage, assessment time points, methodological quality of the study, and study size.Therefore, the high heterogeneity in the stroke subgroup warrants careful interpretation of the overall treatment effect.
Within the PD and MS subgroups, no significant differences were observed, demonstrating that TR yields comparable effects to traditional treatment in improving the QoL for patients with these neurodegenerative pathologies.However, despite the absence of heterogeneity, the limited number of studies in these two subgroups makes it difficult to draw firm conclusions on the comparability of these two modalities for QoL improvement.In the comparisons between synchronous TR and traditional treatment, asynchronous TR, and traditional treatment, as well as mixed TR and traditional treatment, we did not find differences in the improvement of QoL.Examining the overall effect, there seems to be a slightly potentially greater effect in mixed TR as compared to in-person treatment.Furthermore, a subtle positive trend toward asynchronous TR was noted in MS, as well as a positive trend for mixed TR in stroke patients.However, these trends should be approached with caution and further investigation is warranted, particularly in specific comparisons between different treatment methodologies, to better understand their effects on the QoL.
Despite the controversial findings between studies in which some authors found a beneficial effect of TR [25,28], in contrast with other researchers who reported that TR led to inferior results as compared to conventional treatment for QoL and satisfaction levels [29,35], it seems to be a general consesus in considering TR as non inferior to conventional, in-person treatments.This finding is consistent with the present literature on the topic that is focusing on evaluating the effect of TR on clinical outcomes [7,60,61].Nevertheless, as TR is a modality with which we are delivering treatments, attention has to be paid not only to clinical outcomes, but also to the effect that this kind of modality can bring into patients' lives.Indeed, if we think about TR as a modality of treatment delivery, the direct consequence is to think about the content of the exercises and the training proposed through it, which should be evidence-based and with a clinical effect that has already been documented.With this regard, Laver and colleagues already pointed out that "in theory, the mechanisms leading to recovery should mirror those associated with conventional rehabilitation programmes" [62].Given these premises, it is important to look at the strength that TR can bring with it.One of these is, indeed, the benefit to patients' QoL, given the fact that they are at home, in their vocational environment, with their family and carers, and that they do not need to travel to reach the rehabilitation centres.Thus far, studies that have assessed this aspect of TR are limited and with small sample sizes.However, when pooling together data from single studies on the topic, we found that TR positively impacted the QoL levels of patients with neurological impairments, especially in stroke patients.Our study reveals a heightened attention given to stroke within the current body of research, followed by MS and PD.This heightened attention could stem from various factors such as the prevalence of stroke, its impact on patients, or the potential efficacy of TR interventions in addressing the unique challenges posed by stroke-related impairments.Additionally, our analysis indicates a prevalent utilization of asynchronous interventions as the primary mode of TR delivery.This preference may be associated with the adaptability and convenience offered by asynchronous approaches, allowing for tailored interventions, flexibility, and resource optimization.Furthermore, the type of treatment administered, the outcome measures, the technology used, the study size, the treatment intensity, and the duration of follow-ups exhibit heterogeneity even within the same treatment population subgroup.This variability highlights the complexity of implementing TR interventions; recognizing and addressing this heterogeneity is pivotal for advancing our understanding of TR effectiveness and optimizing its application across different clinical scenarios.
When interpreting the results of our meta-analyses, it is imperative to consider the methodological quality of the included studies.As we can observe, the overall methodological quality of the studies raises some concerns when trying to interpret our results and to give some recommendations.The reliability of our findings hinges on the methodological robustness of the individual studies, emphasizing the need for cautious interpretation of our results.Furthermore, it is essential to recognize the differences among MS, stroke, and PD, as these conditions have distinct characteristics that may influence the study's outcomes.Acknowledging the chronic nature of MS and PD, in contrast to the acute nature of stroke, and considering variations in treatments and their diverse impacts on QoL are crucial.Addressing these distinctions as potential limitations ensures a more accurate and transparent interpretation of the study's findings.Additionally, some QoL measures may lack appropriate validation in the telehealth setting and may not exhibit good correlation with each other [5].It is important to acknowledge that the use of patient-reported outcomes as a measure of disability is a limitation, as there may be significant divergence compared to physician-assessed outcomes [63].
Further studies investigating aspects related to the QoL of neurologic patients who undergo physiotherapy treatments in TR are needed, in order to foster the implementation of TR as a modality with which we could guarantee a certain continuity of care and accessibility to rehabilitation services, together with a beneficial effect on patients' QoL, which could in turn have a positive impact on their functional performance.

Study Limitations
The limitations of the present study include a notable heterogeneity across studies, a disproportionate representation of stroke, MS, and PD studies, and the presence of a limited number of studies demonstrating a high methodological quality, which may impact the reliability of the conclusions drawn from this analysis.

Conclusions
Our study demonstrated that motor TR shows a positive and significant impact on the QoL for patients with neurological diseases, including stroke, PD, and MS.The effectiveness is particularly notable in stroke patients, although caution is needed in the interpretation of this result due to the high heterogeneity found in this subgroup.For PD and MS, TR seems to yield comparable results to in-person treatment.Further research, adhering as much as possible to the recommendations for correct reporting is essential to explore the impact of TR on QoL in patients with neurological impairments, an aspect not consistently explored in the studies.It is desirable to conduct more in-depth exploration in neurodegenerative pathologies, as TR can serve as a valuable support for chronic conditions and their monitoring.arterial diseases/de OR intracranial hemorrhages/de OR "brain injuries" OR "brain injury, chronic" OR poststroke OR post-stroke) #2 ("Telerehabilitation"/de OR "Telemedicine"/de OR "Telecommunications"/de OR "telehealth" OR "telemedicine" OR "telerehabilitation" OR videoconferenc* OR teletreatment* OR "teletherapy" OR "Distance Education" OR Telepractice OR "Virtual Conferenc*" OR "Tele-rehabilitation" OR "Remote Rehabilitation") #3 ("randomized controlled trial*"/de OR "randomized controlled trial*" OR "controlled clinical trial*" OR "quasi-randomized control trial*") #1 AND #2 AND #3 WEB OF SCIENCE TS = ("Stroke" OR "Brain Ischemia" OR "Hemorrhagic Stroke" OR "cva" OR "post stroke" OR hemiplegia OR "cerebrovascular disorders" OR "basal ganglia cerebrovascular disease" OR "carotid artery diseases" OR "intracranial arterial diseases" OR "intracranial hemorrhages" OR "brain injuries" OR "brain injury, chronic" OR poststroke OR "post-stroke") TS = ("Telerehabilitation" OR "Telemedicine" OR "Telecommunications" OR "telehealth" OR videoconferenc* OR teletreatment* OR "teletherapy" OR "Distance Education" OR Telepractice OR "Virtual Conferenc*" OR "Tele-rehabilitation" OR "Remote Rehabilitation") WC = (rehabilitation) TS = ("randomized controlled trial*" OR "controlled clinical trial*" OR "quasi-randomized control trial*") #2 (("Telerehabilitation"/de) OR ("Telemedicine"/de) OR ("Telecommunications"/de) OR ("telehealth") OR ("telemedicine") OR ("telerehabilitation") OR (videoconferenc*) OR (teletreatment*) OR ("teletherapy") OR "Distance Education" OR Telepractice OR "Virtual Conferenc*" OR "Tele-rehabilitation" OR "Remote Rehabilitation") #3 "randomized controlled trial*"/de OR "randomized controlled trial*" OR "controlled clinical trial*" OR "quasi-randomized control trial*" #1 AND #2 AND #3
Overall, participants in both groups expressed a high level of satisfaction, perception of ease of use, and a positive attitude toward TR system, with a willingness to recommend it to others.The results showed no significant differences in all items, except for perceived usefulness and perceived satisfaction of system in the TR group.Semi-structured telephone interviews with physiotherapists and participants, investigating their reasons for taking part in the study, their views of the assessments and intervention, any issues faced, the perceived benefit, and recommendations for a future trials.

N/A N/A N/A
The treatment was feasible and acceptable to both participants and physiotherapists, with no intervention-related adverse events.
Notes: * N/A = indicates that the specific outcome was not utilized or investigated in the respective studies.

Figure 2 .
Figure 2. Risk of bias of the included studies (RCTs) 3.4.1.Risk of Bias in Randomized Studies -Bias arising from the randomization process: 17 studies [16,24,28,29,32,34-37,39,42-46,48,49,51] received a low risk of bias while the other 9 raised some concerns.These concerns primarily stemmed from the lack of information regarding participant allocation blinding during the randomization phase.In addition, in one study[26], the experimental group was statistically more active at the baseline; in three studies

Figure 2 .
Figure 2. Risk of bias of the included studies (RCTs).

Table 1 .
Risk of bias in non-RCTs.