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Abstract
Objectives To critically evaluate the effectiveness of physical therapy interventions in improving global function, quality of life and fatigue in individuals with amyotrophic lateral sclerosis (ALS).
Design Systematic review and meta-analyses.
Data sources MEDLINE, EMBASE, Cochrane Library (CENTRAL) and Physiotherapy Evidence Database (PEDro) were searched through 31 January 2023.
Eligibility criteria We included randomised clinical trials (RCTs) that compared physical therapy interventions that act on global function, fatigue and quality of life in individuals with ALS with any other non-physiotherapeutic methods and techniques, placebo or non-intervention. The primary outcome measure was the evaluation of global function. Secondary outcomes were quality of life, fatigue and adverse events.
Data extraction and synthesis Two independent authors used a researcher-developed extraction form and the Rayyan software to search, screen and code included studies. The risk of bias was assessed using the PEDro scale. Meta-analyses were conducted employing random effects. Outcomes were succinctly presented in Grading of Recommendations, Assessment, Development and Evaluation evidence profiles.
Results Our searches identified 39 415 references. After study selection, three studies were included in the review. Such studies involved 62 participants with a mean age of 54.6 years. In the evaluated trials, 40 were male, while 22 participants were female. Regarding the type of onset of the disease, 58 participants had spinal onset of ALS, and four had bulbar.
Conclusions Physical therapy intervention may improve the global function of individuals with ALS in the short term; however, clinically, it was inconclusive. In terms of quality of life and fatigue, physical therapy intervention is not more effective than control in the short term. Adverse events are not increased by physical therapy intervention in the short term. Due to significant methodological flaws, small sample sizes, wide CIs and clinical interpretation, our confidence in the effect estimate is limited.
PROSPERO registration number CRD42021251350.
- systematic review
- rehabilitation medicine
- motor neurone disease
Data availability statement
Data are available upon reasonable request.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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STRENGTHS AND LIMITATIONS OF THIS STUDY
This review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and in accordance with a previously published protocol.
We analysed different types of physical therapy interventions and defined non-intervention as a comparator.
The Grading of Recommendations, Assessment, Development and Evaluation methodology was used to assess the certainty of evidence.
It is possible that we may not have identified references in the grey literature.
We included only randomised controlled trials, as we aimed to conduct high-quality meta-analyses, but this restricted the number of studies found.
Introduction
Amyotrophic lateral sclerosis (ALS) is a progressive and debilitating condition that affects the nervous system, causing the deterioration of motor neurons in the cortex, brainstem and spinal cord.1 This leads to muscle weakness, which causes difficulties with movement, swallowing and breathing, often requiring ventilator support for survival.2 3 Symptom onset types are typically anatomically localised and include extremity muscle deficits, limb onset (spinal), dysarthria or dysphagia symptoms and bulbar onset, with a small fraction presenting with respiratory or generalised weakness onset.4–6 Studies suggest that spinal ALS may be more prevalent worldwide compared with bulbar ALS, with estimates ranging from 58% to 82%.7
In the initial stages of the disease, progressive muscle weakness may manifest and show asymmetry between the upper and lower limbs, resulting in decreased functional ability and adversely impacting quality of life.8 The rate of progression varies among individuals but typically starts with one anatomical region involvement before spreading to other body regions. Fatigue, experienced as a generalised sense of tiredness and challenges with maximum muscle contraction, is also commonly reported by individuals with ALS.9 Additionally, patients can present upper motor neuron signs, such as spasticity and rigidity, lower motor neuron signs, such as hypotonia, or a mixed functional presentation, with a combination of both depending on the region.10
Given the severe prognosis and nature of ALS, treatment primarily involves personalised general care.11 Pharmacological options are limited, with only a few drugs approved by the Food and Drug Administration offering modest effects on the disease’s drastic effects.12 Clinical management of ALS is complex and requires a multidisciplinary approach to address the various challenges faced by individuals with ALS. Physical therapy plays a fundamental role within the multidisciplinary team, tailored to the specific needs and goals of each individual. The physical therapist plays a crucial role in managing symptoms, optimising functions and activities, enhancing participation and improving the overall quality of life for individuals with ALS.13
When applied by a physical therapist, a physical activity involving a range of motion and stretching exercises is generally well accepted by individuals with ALS. Resistance exercises targeting unaffected muscles (or affected muscles with strength graded at least 3 or higher) using low to moderate loads, as well as aerobic activities at submaximal levels (around 50%–65% of heart rate reserve) such as swimming, walking and stationary cycling, can be considered safe and effective in achieving therapeutic objectives.14 Aerobic and resistance exercises can be prescribed and recommended for patients in the early and intermediate stages after diagnosis, as well as those with a slower rate of disease progression.13
Physical therapists face challenges when prescribing intervention plans for individuals with ALS due to the disease’s diverse clinical phenotypes, individual prognosis and rapid progression rate, which pose challenges in managing its deteriorating effects.15 There is an increasing acceptance of the hypothesis that appropriately prescribed exercises in the early stages of the disease may benefit individuals with ALS.16 Furthermore, multiple studies evaluating physical therapy exercises or motor techniques in ALS have demonstrated improvements in physical function, quality of life and fatigue.9 17 18 Furthermore, the effects of physical therapy interventions, including resistance and aerobic exercises, etc, on individuals with ALS are subjects of debate in the literature due to uncertainties regarding the clinical effectiveness and safety of exercise.18
Recent systematic reviews addressed this topic18 19; however, these studies established ‘usual care’ as a comparator. On the other hand, this review established that the comparator was no intervention or other non-physiotherapeutic method. Therefore, the objective of this review is to critically evaluate the effectiveness of physical therapy interventions in improving global function, quality of life and fatigue in individuals with ALS.
Methods and analysis
This systematic review was reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards20 and a previously published protocol.21 This study has been registered in the International Prospective Register for Systematic Reviews under number CRD42021251350.
Eligibility criteria
Study types
In our systematic review, we considered randomised clinical trials (RCTs) that involved physical therapy as an intervention for individuals with ALS. We considered data from the first phase of cross-over studies. Quasi-experimental and non-randomised studies were excluded from our analysis.
Participants
We considered participants of both sexes who had a clinical or probable diagnosis of ALS at any stage of the disease, without any other neurological disease and were aged 18 or above.
Interventions and comparators
We defined intervention as any physical therapy intervention that acts on symptoms in individuals with ALS. This included therapeutic exercises, stretching, aerobic exercises, relaxation techniques, massage therapy, electrostimulation and energy conservation techniques. We did not consider studies that used interventions in respiratory physical therapy. The control group consisted of any other non-physiotherapeutic methods and techniques, placebo or non-intervention.
Outcome measures
The primary outcome measure for our review was the evaluation of global function using the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)22 ;
Secondary outcomes were quality of life (measured by tools such as the 36-Item Short Form Health Survey (SF-36)),23 ALS Assessment Questionnaire,24 ALS Specific Quality of Life-Revised25 or McGill Quality of Life Questionnaire),26 fatigue (measured by the Modified Fatigue Impact Scale,27 Fatigue Severity Scale (FSS)28 or Neurological Fatigue Index-motor neuron disease29), as well as any adverse events that occurred during the study period.
Search method
We selected studies based on eligibility criteria without any language, geographical area or publication date restrictions. We searched four databases, namely, MEDLINE, EMBASE, the Cochrane Library (CENTRAL) and the Physiotherapy Evidence Database (PEDro). Additionally, we conducted searches on ClinicalTrials.gov (www.clinicaltrials.gov/) and reviewed the reference lists of included studies. After reading the full-text articles, we excluded studies that did not meet the inclusion criteria, and the reasons for exclusion were recorded. Searches were conducted in January 2023.
Search strategy
We have developed a search strategy (see online supplemental file 2) using the MEDLINE database, which has been adapted for other databases. The search covered terms related to symptoms, such as global function, quality of life and fatigue in the context of ALS. Descriptors related to various aspects of ALS, intended outcomes and physical therapy techniques were included in English. We did not employ MEDLINE/Embase subject headings or keywords in our search strategy.
Supplemental material
Data extraction
The titles and abstracts of references were verified by two independent authors (STS and KP) using the Rayyan software (Intelligent Systematic Review).30 Duplicate studies and those that failed to meet the criteria were removed by the researchers. Inconsistencies were resolved through discussion or consultation with a third author (TSR), and the entire process was documented in a PRISMA flowchart.
Data extraction from the included studies was also conducted by the same authors (STS and KP) using a researcher-developed extraction form. In cases of missing or uncertain data, the authors were contacted for clarification.
Time of evaluation
We collected outcome data at three time points: baseline, end of the intervention (to assess immediate effects) and follow-up (to assess medium-term and long-term effects). Medium-term effects were measured between 1 week and 6 months following the treatment, and long-term effects were measured after 6 months.31
Risk of bias assessment
To assess the quality of the included studies, we used the PEDro scale,32 which comprises 11 criteria that evaluate methodological rigour. Each criterion is scored on a scale of 0–10, with higher scores indicating higher methodological quality.
Data analysis and processing
Statistical analysis was conducted using Cochrane’s Review Manager Web.33 For continuous outcomes with the same tools and measurement units, the weighted mean difference was chosen. In cases where tools and measurement units did differ, the standardised mean difference was used. Additionally, 95% CIs were calculated. For dichotomous outcomes, such as adverse events, the OR and 95% CIs were used to assess treatment effects. We only use data from the end of the studies since the studies found did not provide medium-term and long-term results in sufficient quantity to carry out meta-analyses.
For the clinical interpretation of the meta-analysis, we employed minimal clinically important differences (MCID). Regarding global function (ALSFRS-R), we considered 20% of the total score.34 35 For other outcomes such as quality of life and fatigue, MCID values (SF-36, McGill Quality of Life and FSS) were set at 10%, as there is currently no consensus on the MCID for these outcomes.36 It is worth noting that the MCID for ALSFRS-R (scale: 0–48) was determined to be 9.6 points, SF-36 (scale: 0–100) was 10 points, the McGill Quality of Life Questionnaire (scale: 0–10) was 1 point and FSS (total score: 63) was 6.3 points. The results were then categorised as follows:
Effective: if the 95% CI of the mean between-group difference was above the MCID.
Inconclusive: if the 95% CI of the mean between-group difference spanned the MCID.
Ineffective: if the 95% CI of the mean between-group difference was below the MCID.36
Heterogeneity
Heterogeneity among studies was assessed using χ2 and I2 values. We used the random-effects model for meta-analysis. When significant heterogeneity was detected between studies (p<0.1, I2>50%), subgroup analyses were conducted to investigate the source of heterogeneity.
Meta-analyses
Meta-analyses were performed using Cochrane’s Review Manager Web33 when studies exhibited clinical and methodological similarities. The studies were grouped to compare the effects of:
Physical therapy intervention versus control (no intervention and non-physiotherapeutic method).
We intended to perform meta-analysis grouping studies with the following characteristics. (1) Physical therapy intervention versus placebo and (2) physical therapy intervention versus educational and orientation programmes. However, it was impossible because the number of studies was insufficient. The follow-up meta-analysis (medium-term and long-term effects) was not performed because only one study had data available for all outcomes.
Dealing with missing data
When we realised there were any instances of missing data, such as statistical or relevant study-related information, we reached out to the lead author via email to request additional details. In the event of data loss or no response from the author, a descriptive analysis was conducted.
Subgroup analyses
We performed the following subgroup analysis:
Type of treatment: manually, mixed (manually and equipment) and educational/awareness approach.
We intended to perform other subgroup analyses, such as (1) type of disease onset: spinal or bulbar; (2) disease duration: less or more than 5 years; (3) age: less than or above 60 years and (4) treatment dose: once to twice a week and more than twice a week. However, these analyses were not performed because the data were not made available, even after requesting the authors of the primary studies.
Sensitivity analysis
No peripheral studies were found that would justify carrying out this type of analysis.
Assessment of certainty of evidence
The quality of studies included in the meta-analyses was assessed using the five components of the Grading Quality of Evidence and Strength of Recommendations (GRADE), which include study limitations, inconsistency, imprecision, indirectness and publication bias.37 The overall quality of evidence was categorised as high, moderate, low or very low.37
Protocol changes for the review
We included additional groups for subgroup analysis related to the type of treatment in the experimental group. In addition to the manually applied subgroup, we created a mixed subgroup composed of physical therapy applied both manually and using equipment (such as a cycle ergometer and treadmill, among others) and an educational/awareness approach group composed of energy conservation techniques. We excluded the equipment-only group established in the protocol, as studies including only this type of intervention were not observed in the included studies.
Patient and public involvement
Patients were not involved in this study.
Results
Our searches identified a total of 39 415 references. After the study selection and removal of duplicates, we identified 14 potentially eligible references. After full-text reading, three studies were included in the review. The PRISMA flow chart summarises the results of the search (figure 1).
Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram describing study selection.
Characteristics of included studies
All the included studies were RCTs. The three studies involved a total of 62 participants, with a mean age of 54.6 years. In the evaluated trials, 40 participants were male, while 22 participants were female. As for the type of onset of the disease, 58 participants had spinal-onset ALS and four had bulbar. One study was conducted at the participant’s home,38 while two others were conducted at clinics.39 40
Outcome measures
The global function outcome was assessed in two studies,38 40 and in both studies, the authors used the ALSFRS-R. Fateh et al39 used the same instrument to characterise the sample. The quality of life outcome was assessed in all three included studies. The SF-36 instrument was used in two studies,38 39 and the McGill Quality of Life Questionnaire was used in one study.40 The fatigue outcome was assessed using the FSS in two studies.38 39
Interventions and comparators
Physical therapy interventions applied in the studies included resistance exercises, strengthening exercises, aerobic exercises, balance exercises, stretching exercises and energy conservation techniques. The comparators were a non-physiotherapeutic technique (occupational therapy) and no intervention with maintenance of usual activities. The studies varied in duration and frequency. Drory et al38 lasted 3 months, with each session lasting 15 min and taking place two times a day. Fateh et al39 lasted 3 weeks, with each session lasting 1 hour per week. In contrast, Ferri et al40 extended for 12 weeks, with each session lasting 1 hour and taking place three times per week. For further details, please refer to the online supplemental table.
Supplemental material
Risk of bias in included studies
Only one out of the three included studies40 was classified as having sufficient methodological rigour (≥5)41 (see online supplemental table). All studies had adequate randomisation. Allocation concealment was not ensured in any of the included studies. Groups were similar at baseline in all trials. Participants, therapists and assessors were not blinded in any of the studies. Outcome data were available in over 85% in only one study. An intention-to-treat analysis was used in one of the trials. Statistical comparison between groups occurred in all studies. Point estimates and outcome variability data were reported in two of the trials.
Supplemental material
Medium-term and long-term effects
We intended to conduct an analysis of data related to the medium-term and long-term effects. However, we were unable to perform the follow-up analyses due to insufficient studies for grouping the data in the meta-analysis. Only one study39 provided data related to medium-term effects. The study indicated improvements in fatigue (assessed by FSS) and quality of life (assessed by SF-36) 1 month after the intervention concluded.
Quantitative synthesis of studies: meta-analyses
We conducted meta-analyses that assessed the outcomes of global function, quality of life, fatigue and adverse events. All meta-analyses were based on data extracted at the end of the intervention (immediate effects).
Immediate effects
Physical therapy intervention versus control: global function
Two studies (34 participants) assessed global function using the ALSFRS-R. Physical therapy intervention is more effective than control in improving global function (pooled mean difference (MD)=10.13; 95% CI 4.78 to 15.48; p=0.0002; I2=56%; figure 2). Considering the previously established MCID (9.6), the result was inconclusive.
Effects on global function.
Subgroup analysis: type of treatment in the experimental group
Subgroup analyses were performed based on the experimental group’s type of treatment (two studies, 34 participants) and grouped the studies in which participants underwent (1) physical therapy intervention applied manually and (2) a physical therapy intervention applied manually with the aid of equipment such as a cycle ergometer and treadmill, among others (mixed). In all subgroups, statistical significance was observed in favour of the experimental group. There was no significant intergroup difference (p=0.13; I2=56.3%). Considering the previously established MCID, the results of subgroups were inconclusive. See online supplemental figure.
Physical therapy intervention versus control: quality of life
Three studies (62 participants) compared the effects of physical therapy intervention on quality of life using different measures (McGill Questionnaire and SF-36). Physical therapy intervention is not more effective than the control group in improving quality of life (pooled standardised MD (SMD)=0.39; 95% CI −0.35 to 1.13; p=0.30; I2=49%; figure 3). Due to the use of different instruments in the studies, we analysed the CIs of each study separately for clinical interpretation. Drory et al38 and Fateh et al39 used SF-36, and the results were ineffective (MCID=10). Ferri et al40 employed the McGill Quality of Life Questionnaire, and the result was inconclusive (MCID=1).
Effects on quality of life.
Subgroup analysis: type of treatment in the experimental group
We analysed subgroups considering the type of treatment in the experimental group (three studies, 62 participants) and grouped the studies in which participants received (1) physical therapy intervention applied manually with the aid of some equipment such as a cycle ergometer and treadmill, among others (mixed); (2) educational/awareness approach (energy conservation strategies); and (3) physical therapy intervention applied manually (manually). In the mixed subgroup, statistical significance was observed in favour of the experimental group (SMD=1.18; 95% CI 0.09 to 2.27; p=0.03; I2=not applicable). There was no significant intergroup difference (p=0.14; I2=49.2%). Considering the MCID, the result of group 1 was inconclusive, while results of subgroups 2 and 3 were ineffective. See online supplemental figure.
Physical therapy intervention versus control: fatigue
Two studies (46 participants) measured fatigue using the same measure (FSS). Physical therapy intervention is not more effective than the control group in reducing fatigue at the end of the intervention (pooled MD=−4.80; 95% CI −16.09 to 6.50; p=0.41; I2=77%; figure 4). Considering the previously established MCID (6.3), the result was inconclusive.
Effects on fatigue.
Subgroup analysis: type of treatment in the experimental group
We analysed subgroups considering the type of treatment in the experimental group (two studies, 46 participants), and grouped the studies in which participants received (1) an educational/awareness approach (energy conservation strategies) and (2) physical therapy intervention applied manually. In the subgroup of studies with manual physical therapy intervention, there was a statistically significant difference favouring the control group (MD=−12.10; 95% CI −23.32 to −0.88; p=0.03; I2=not applicable). The intergroup differences were statistically significant (p=0.04; I2=76.6). Considering the previously established MCID, the results of subgroups were ineffective. See Supplemental Figure.
Adverse events
Two studies reported adverse events of any nature. Fateh et al39 reported issues with transportation and quarantine. Ferri et al40 reported worsening of overall disease condition, depression, gastrostomy and difficulty in reaching the treatment location. Drory et al38 did not report monitoring or occurrence of adverse events.
Physical therapy intervention versus control: adverse events
Two studies (41 participants) reported adverse events of any nature, which were grouped in a meta-analysis. Physical therapy intervention does not increase the odds of adverse events of any nature compared with interventions with the control group (OR=0.61; 95% CI 0.07 to 4.94; p=0.64; I2=49%; figure 5).
Adverse events meta-analysis.
Assessing certainty in evidence
There were serious and very serious concerns in three domains of the GRADE (risk of bias, inconsistency and imprecision) in all three included studies. The certainty of the evidence was rated as very low for all evaluated outcomes: global function, quality of life, fatigue and adverse events. The assessment of the certainty of the evidence and the reasons for downgrading are presented in table 1.
Assessing certainty in evidence
Discussion
The aim of this review was to critically evaluate whether physical therapy intervention is effective in improving global function, quality of life and fatigue in individuals with ALS. Compared with controls (no intervention), we found that physical therapy interventions improved global function with very low-quality evidence. Physical therapy intervention also improved global function regardless of the type of treatment (manually applied physical therapy and mixed (manual and equipment-based) physical therapy). However, there was no significant difference between the groups according to treatment types. We observed wide CIs and considerable heterogeneity among the studies that reported this outcome.
The evidence found was of very low quality that physical therapy intervention does not improve quality of life when compared with control. Regarding the type of treatment, we found statistical significance in favour of the experimental group, which was composed of physical therapy interventions performed both manually and using equipment. However, there was no intergroup difference (manual, mixed and educational/awareness approach).
Regarding fatigue, we found evidence of very low quality that physical therapy intervention is not more effective compared with control. In terms of treatment type, we found statistical significance in favour of the control group, which underwent physical therapy intervention performed only manually. There were statistically significant differences between the groups (manual and educational/awareness approach). We observed high heterogeneity among studies that assessed fatigue.
We found evidence of very low quality that physical therapy intervention does not increase the chance of adverse events of any nature. We grouped studies that reported various adverse events, including those related to health conditions and those unrelated, such as patients who did not complete the treatment or were unable to reach the intervention site. We were unable to assess the effects of physical therapy intervention in the medium and long term, as we did not have a sufficient number of studies for any of the outcomes observed. Fateh et al39 presented information regarding the medium-term effects. The authors inferred improvements in quality of life and fatigue; however, this study had some limitations, such as a short duration of treatment and a high risk of bias.
Our search found a significant number of studies that used physical therapy interventions in an attempt to improve symptoms in individuals with ALS. However, due to eligibility criteria and the intention to observe the effect of the intervention compared with a comparator that did not have direct similarities with the treatment, few studies could be included; furthermore, these studies had small sample sizes. From this, we infer that there are factors that generate uncertainties for generalisations. It should be noted that our results were related only to short-term effects (immediately after the intervention). In addition, due to the brevity of the interventions in the studies, it is possible that no significant changes occurred as a result of these interventions. For example, Meng et al18 emphasised that changes in the global function of individuals with ALS may only become evident in the long -term, and the positive effects of exercise may require an extended duration to manifest.18
Our clinical interpretation of the meta-analyses was based on the MCID. The MCID (20%) for ALSFRS-R has been established in some previous studies.34 35 For the other instruments (FSS, SF-36 and the McGill Quality of Life Questionnaire), we set it at 10% based on a systematic review that used this value for instruments without a defined MCID.36 The lack of establishment of the MCID makes us cautious when considering only clinical significance. On the other hand, the statistical analysis from a systematic review with meta-analysis is more robust and provides us with a more secure direction regarding the obtained results. Of note, the importance of clinical interpretation in our meta-analyses provides an opportunity for a debate on statistical difference versus clinical significance. Furthermore, the use of an MCID ensures that the statistically significant effects are not automatically assumed to translate into clinical relevance.36
Our global function result (ALSFRS-R) indicated a statistical difference in favour of the intervention; however, upon considering the MCID, we recognise it as an inconclusive result. As for the outcomes of fatigue and quality of life, inconclusive and ineffective results were observed. These findings underscore the need to consider not only statistical differences but also clinical significance before determining the optimal treatment. Furthermore, they also highlight the low certainty regarding the actual effectiveness of physical therapy in alleviating symptoms in individuals with ALS.
The dilemma is no longer whether exercise can benefit patients with ALS or induce muscle distress and contribute to progressive weakening. According to several recent studies, exercise can act as a protective factor in ALS, especially in early cases of the condition.42 It is recommended that the physical therapist personalise the treatment plan according to the individuality and stage of the condition of each patient. The literature suggests that the combination of aerobic training with resistance training (below maximum effort) is associated with positive effects on symptoms in individuals with ALS.42
Based on our findings, we suggest conducting new randomised trials that address physical therapy in the management of symptoms of ALS and have larger sample sizes. However, we recognise the difficulty of conducting such studies in this population. One of the major challenges of conducting clinical trials in ALS is the extensive clinical heterogeneity of patients and the short survival time.43 Researchers in more recent clinical trials attempt to reduce the study duration to overcome this challenge.44 Nevertheless, even with the decrease in study duration, a significant number of individuals may pass away during the study.45 All these losses can introduce important biases in the final results of randomised trials.46
We identified two systematic reviews with meta-analysis similar to ours. Meng et al18 evaluated the efficacy and safety of exercise for individuals with ALS. The experimental interventions listed were resistance or strengthening exercises, aerobic or endurance exercises, respiratory muscle training and others. The comparators were no exercise or usual care (range of motion exercises and stretching). The author included seven studies involving 322 participants. For global function, Meng et al18 indicated that there was no significant effect of exercise when compared with control in the short term (SMD, 0.09; 95% CI, −0.07 to 1.88; p=0.07). The disparity in findings between our study and Meng et al18 may be due to their use of different measurement scales for global function and the inclusion of a range of motion exercises and stretching in their comparator, which differs from our review.
Dal Bello-Haas and Florence47 evaluated therapeutic exercise for individuals with ALS. As an experimental intervention, the author listed stretching, resistance exercises and aerobic exercises. For the control group, the author defined it as no exercise or usual care (range of motion exercises and stretching). Two studies involving 43 participants were included. Similar to our findings, the author inferred that global function had a significant effect in favour of exercise (MD=3.21; 95% CI 0.46 to 5.96). Dal Bello-Haas and Florence47 used only the ALSFRS-R to assess the measurement of the effect of global function.
Strengths and limitations
This review was conducted following the PRISMA guidelines and in accordance with a previously published protocol21 (see online supplemental file). The review has the distinction of evaluating a large number of physical therapy intervention techniques used in the treatment of symptoms in individuals with ALS; furthermore, we defined distinct comparators (no intervention) in comparison to previous reviews. Additionally, we assessed evidence quality using the GRADE system, which provides another positive distinction. Our search strategy was comprehensive, and the study selection process was rigorous. However, we may not have identified references in the grey literature. Another limitation of our review was the eligibility criteria; we included only RCTs, as we aimed to conduct high-quality meta-analyses, but this restricted the number of studies found. Future systematic reviews should include observational studies in the qualitative analysis.
Supplemental material
Implications for practice
According to our results, physical therapy interventions may provide short-term benefits in global function when compared with no intervention or other non-physiotherapeutic method/technique. In terms of quality of life and fatigue, physical therapy intervention was not more beneficial than the comparator group with short-term effects. Regarding adverse events, physical therapy intervention does not increase the likelihood of their occurrence in the short term. It was not possible to estimate the effect of medium-term and long-term interventions. For all outcomes assessed, the certainty of evidence was classified as very low. There were significant methodological concerns, such as small sample sizes and wide CIs in the studies. Therefore, we remain cautious in interpreting the results found, primarily due to the clinical interpretation indicating inconclusive and ineffective results for the assessed measures.
Conclusion
Physical therapy intervention may improve the global function of individuals with ALS in the short term; however, clinically, it was inconclusive. In terms of quality of life and fatigue, physical therapy intervention is not more effective than the control in the short term. Adverse events are not increased by physical therapy intervention in the short term. Due to significant methodological flaws, small sample sizes, wide CIs and the clinical interpretation provided by MCID, our confidence in the effect estimate is limited. More studies are needed in order to evaluate the impact of physical therapy interventions on these outcomes.
Data availability statement
Data are available upon reasonable request.
Ethics statements
Patient consent for publication
Ethics approval
Not applicable.
Acknowledgments
The authors thank the Laboratory of Technological Innovation in Health (LAIS) of the Federal University of Rio Grande do Norte.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
X @luprotasio, @vanessaresqueti, @ricvalentim
Contributors STS: guarantor, conceptualisation, data extraction, risk of bias assessment, statistical analysis, methodology, project administration, writing and editing. IMC: study selection and data extraction. AAS: study selection. KP: risk of bias assessment. LPM: research concept and reviewing. VRR: research concept and reviewing. RV: funding acquisition. FG: review. TSR: conceptualisation, statistical analysis, methodology, project administration and reviewing.
Funding This study was partially supported by the Coordination for the Improvement of Higher Education Personnel, Brazil (CAPES), Finance Code 001, the National Council for Scientific and Technological Development and the Ministry of Health through a Decentralised Execution Term (TED132/2018).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.