Effectiveness of aquatic versus land physiotherapy in the treatment of peripheral neuropathies: a randomized controlled trial.

OBJECTIVE: To compare the effects on gait and balance of aquatic physiotherapy versus on-land training, in the context of an inpatient rehabilitation treatment tailored for peripheral neuropathies.
DESIGN: Parallel-group, single-center, single-blind randomized controlled trial. SUBJECTS AND
SETTING: Consecutive patients affected by peripheral neuropathy admitted in our Neuro-Rehabilitation Unit.
INTERVENTIONS: Patients received a four-week rehabilitation program composed by daily sessions of conventional physiotherapy and three sessions/week of specific treatment (aquatic vs. on-land). MAIN MEASURES: Primary outcome measures were Berg Balance Scale and Dynamic Gait Index. Secondary outcome measures were Neuropathic Pain Scale, Overall Neuropathy Limitations Scale, Functional Independence Measure, Functional Ambulation Classification, Conley Scale and Medical Research Council Scale score for the strength of hip and ankle flexor and extensor muscles. For each scale, we calculated the difference between the scores at discharge and admission and compared it between the two groups.
RESULTS: Forty patients were enrolled: 21 in the water-based rehabilitation group and 19 in the land-based one. Patients were similar between groups. When comparing the groups, we found that "in-water" patients had a significant better improvement in the Dynamic Gait Index score (6.00 (4.00, 7.25) vs. 4.00 (1.25, 6.00), P = 0.0433). On the opposite, the "on-land" group showed a better improvement of the Functional Ambulation Classification score (1.0 (0.75, 1.0) vs. 1.0 (1.0, 2.0), P = 0.0386).
CONCLUSION: Aquatic physiotherapy showed an effect comparable to the land-based rehabilitation on gait and balance dysfunctions of neuropathic patients.

RCT Entities:   Population Interventions Outcomes

Introduction

Rehabilitation is widely recommended as an effective strategy in the management of peripheral neuropathies, useful to maximize the patients’ physical disability and to maintain their quality of life.[1] Indeed, despite the lack of consistent data about its effect on the functional outcome of neuropathic patients,[2] physical exercise was shown to improve neuropathic symptoms,[3] balance and proprioception.[4]

Aquatic therapy is a rehabilitative approach proposed for different medical conditions: the aquatic environment facilitates patients with functional limitations, who feel a safer setting and are consequently more motivated to the training. The physical properties of water help to improve patient stability and to allow limbs movements, by offloading the body weight, exerting resistance against the body segments and giving proprioceptive inputs. Moreover, the warmth of a physiotherapy pool helps muscle relaxation and seems to reduce pain perception.[5]

Several authors evaluated aquatic therapy as possible gait and balance training of neurological patients and demonstrated beneficial effects mostly in Parkinson’s disease and stroke.[6] A limited number of studies, even if affected by small sample sizes, made a comparison between aquatic and on-land training, showing best balance results of the former for the same diseases.[7-10]

Stating the initial promising results of aquatic therapy and the absence of studies exploring its effects in peripheral neuropathies, the main symptom of which is a balance dysfunction, we wanted to compare the effects of a water-based training in the context of a land-based rehabilitative program and the land-based rehabilitation alone on balance and gait of neuropathic patients.

Methods

This is a parallel-group, single-center, single-blind randomized controlled trial. The study was approved by the local research ethics committee (“Comitato Etico Interaziendale delle Province di Lecco, Como e Sondrio”) and registered in the ClinicalTrial.gov website (registration number NCT02714517). The study has been performed in accordance with the ethical standards laid down in the Declaration of Helsinki, its later amendments and the national laws. All the patients involved signed a written informed consent for the participation to the study.

Consecutive patients affected by a peripheral neuropathy admitted in our Neuro-rehabilitation Unit were screened by a neurologist. Inclusion criteria were a diagnosis of peripheral neuropathy (according to clinical and EMG data) of any etiology, the presence of a motor deficit in the lower limbs due to the neuropathy and the ability to maintain the upright position and to walk even if with assistance. Exclusion criteria were the presence of severe cardiovascular and respiratory diseases, other neurological diseases, a rehabilitation treatment in the previous six months, wounds or bedsores, skin diseases, urinary incontinence and fear of water.

The enrolled patients were randomly assigned to the experimental or to the control group using a web-based application (www.randomization.com). The block randomization method (block size of 4) was chosen to ensure balance in sample size across groups over time. The randomization procedure was ran by a single investigator and the allocation of each participant was concealed until assignment.

All patients underwent a four-week inpatient rehabilitation program tailored for peripheral neuropathies and composed by the following daily sessions: (1) conventional one-to-one training with a physical therapist (1 hour/day, five days/week); (2) devices training with the supervision of a physical therapist (treadmill, cycloergometer, cyclette, stabilometric platform; 1 hour/day, six days/week); (3) Occupational Therapy (1 hour/day, five days/week).

Three days per week (Monday, Wednesday, Friday) the first session was performed with a specific one-to-one training in one of two different environments, according to the group: a heated (32°C) swimming pool for the experimental (“in-water”) group and “on-land” for controls. The training was run by a physiotherapist expert in aquatic therapy and was composed by a set of exercises chosen by our group in order to be performed both in water and on land. These sessions were carried out through the following steps: (1) relaxation and breath control; (2) balance and posture control exercises; (3) gait exercises (see Supplementary Appendix 1). Therefore, the primary difference between the two groups was that in the experimental one, for 3 hours a week, one-to-one face-to-face balance and gait training on land was replaced by the same training in an aquatic environment.

We collected data about age, sex, timing of neuropathy (acute or chronic) and presence of sensorial deficit in the lower limbs. The primary outcome measures were as follows:

– Berg Balance Scale, measuring the static balance and fall risk;[11]

– Dynamic Gait Index, assessing the ability to adapt gait to complex tasks.[12]

Secondary outcome measures were as follows:

– Neuropathic Pain Scale, evaluating distinct qualities of neuropathic pain;[13]

– Overall Neuropathy Limitations Scale, measuring the impairment in the everyday activities and quality of life of neuropathic patients;[14]

– Functional Independence Measure, assessing the level of patients’ disability and the need of assistance in the activities of daily living.[15]

– Functional Ambulation Classification, evaluating the ability and independency of walking;[16]

– Conley Scale, assessing the risk of falls;[17]

– Medical Research Council Scale score, evaluating, in our case, the strength of the flexor and extensor muscles of the hip and ankle.[18]

All the abovementioned scales were assessed on the first and last day of the four-week rehabilitation program by a physiotherapist blinded to the treatment allocation and to the study design, who collected the outcomes data in a specific database.

We computed the sample size to detect a difference in the change (discharge-admission) in Berg Balance Scale of at least 3 between the experimental and the control groups. Since the standard error of measurement for the Berg Balance Scale in patients affected by a peripheral neuropathy is not known, we assumed a value equal to 1.8 from studies carried out in different populations.[19] Hence, to highlight the established difference with a two-tailed type I error of 0.05 and a power of 80%, the estimated sample size was 13 patients per group. Making a conservative choice, that takes into account an attrition rate as high as 33%, we increased the sample size to 40 patients.

We anticipated that in case the trial would fail to detect a significant difference between the two rehabilitation strategies, the objective might be downgraded to show non-inferiority. Accordingly, we predefined a non-inferiority margin equal to 3 for Berg Balance Scale and 1.8 for Dynamic Gait Index. Both values were determined considering the Minimal Clinically Important Difference reported in studies carried out in different populations.[19,20]

The Shapiro–Wilk statistic was used to test the normality of the distribution of all variables. Most outcome variables were non-normally distributed, with severe violations to the normality assumption. Accordingly, descriptive statistics are reported as median (lower quartile, upper quartile) and between-group comparison were carried out by the Mann–Whitney U-test. To compare the effectiveness on balance and gait of water-based physiotherapeutic treatment and land-based rehabilitation alone, we computed the difference between the discharge and admission values. Since these differences did not show marked departures from the normal distribution, results are presented as mean ± SD and between-group comparison were carried out by unpaired t-test. All results were checked using also non-parametric Mann–Whitney U-test.

Comparisons of categorical variables were carried out with the chi-square test. Age was reported as mean ± SD and between-group comparison carried out by unpaired t-test.

The standardized mean difference was also computed and used to assess the effect size. The following thresholds were used to classify the effect size respectively as small, medium, large and very large: 0.2, 0.5, 0.8 and 1.3.

All statistical tests were two-tailed and statistical significance was set at P < 0.05. All analyses were carried out using the SAS/STAT statistical package, release 9.4 (SAS Institute Inc., Cary, NC, USA). Supplementary materials are available under request to the corresponding author.

Results

Figure 1 shows the trial profile. Since there were no dropouts and all patients completed the treatment originally allocated, intention to treat analysis and per protocol analysis coincide. Patients in the two groups had similar age, gender distribution, presence of sensorial deficit in the lower limbs and disease timing (Table 1).

Figure 1.

CONSORT flow diagram.

Table 1.

Basal values for demographic and clinical variables subdivided according to the rehabilitation strategy.

Variable	“In-water” (N = 21)	“On-land” (N = 19)	P-value
Males	11	8	0.52
Age (years)	66.3 ± 13.0	71.8 ± 7.7	0.20
Acute PN	5	3	0.53
Hypoesthesia lower limbs	13	14	0.43

P-value: P-value for between-group comparison—unpaired t-test for age and chi-square test for dichotomous variables; PN: polyneuropathy.

Age is reported as mean ± SD. Dichotomous variables are reported as N.

Table 2 reports admission and discharge values for all outcome variables in both groups of patients. The between-group comparison of baseline values revealed that “On-land” patients had more compromised Berg Balance Scale, Dynamic Gait Index, Overall Neuropathy Limitations Scale, Functional Independence Measure, Functional Ambulation Classification and Medical Research Council Scale score for hip flexors.

Table 2.

Outcome variables in experimental and control groups.

Variable	“In-water” admission	“In-water” discharge	“On-land” admission	“On-land” discharge
BBS	36.0 (32.0, 42.0)	51.0 (43.0, 54.0)	31.0* (23.0, 33.0)	41.0 (35.0, 50.0)
DGI	15.0 (13.0, 18.0)	21.0 (18.8, 23.3)	11.0* (8.3, 14.8)	15.0 (13.0, 19.5)
NPS	5.00 (4.00, 7.00)	5.00 (2.75, 6.00)	6.00 (4.25, 7.75)	6.00 (4.00, 7.00)
ONLS	2.00 (2.00, 2.00)	2.00 (1.00, 2.00)	4.00** (2.00, 4.00)	2.00 (1.25, 4.00)
FIM	88.0 (81.5, 89.0)	112.0 (103.8, 120.3)	81.0* (78.0, 86.0)	103.0 (96.0, 120.8)
FAC	4.00 (3.00, 4.00)	5.00 (4.00, 5.00)	3.00** (2.00, 3.75)	4.00 (4.00, 5.00)
CONLEY	4.00 (2.75, 5.00)	2.00 (2.00, 3.00)	4.00 (3.00, 4.00)	3.00 (2.00, 4.00)
MRC hip flexors	3.00 (3.00, 4.00)	4.00 (3.00, 4.00)	3.00* (3.00, 3.00)	4.00 (4.00, 4.00)
MRC hip extensors	3.00 (2.75, 3.00)	4.00 (3.00, 4.00)	3.00 (3.00, 3.00)	4.00 (3.25, 4.00)
MRC ankle flexors	3.00 (2.00, 3.25)	4.00 (3.00, 4.00)	3.00 (2.00, 3.00)	4.00 (2.25, 4.00)
MRC ankle extensors	3.00 (2.00, 3.00)	3.00 (2.75, 4.00)	3.00 (2.00, 3.00)	4.00 (3.00, 4.00)

BBS: Berg Balance Scale; DGI: Dynamic Gait Index; NPS: Neuropathic Pain Scale; ONLS: Overall Neuropathy Limitations Scale; FIM: Functional Independence Measure; FAC: Functional Ambulation Classification; MRC: Medical Research Council Scale.

Data are reported as median (lower quartile, upper quartile).

P < 0.05 for the comparison with “In-water” admission values; **P < 0.01 for the comparison with “In-water” admission values.

All outcome measures significantly improved after treatment in both groups (all P < 0.01), except Overall Neuropathy Limitations Scale in the “in-water” group (P = 0.27) and Neuropathic Pain Scale in the “on-land” group (P = 0.46). The differences (discharge – admission) are reported in Table 3 together with the effect size. The P-values for the between-group comparison (unpaired t-test) of changes are also reported. The same comparisons were carried out with non-parametric tests, obtaining superimposable results. It can be seen that only the differences in Dynamic Gait Index, Functional Ambulation Classification and the Medical Research Council Scale for hip flexors were significantly different in the two groups. Focusing on the primary outcome measures, Dynamic Gait Index resulted to have a higher improvement in the “in-water” group (P = 0.04) demonstrating superiority, while no significant difference was observed for Berg Balance Scale (P = 0.86). Comparing the 95% confidence interval for Berg Balance Scale with the prespecified non-inferiority limit, non-inferiority was shown (P = 0.024). Differently, Functional Ambulation Classification and Medical Research Council Scale of the hip flexors improved more in the “on-land” one (P = 0.039 and P = 0.013, respectively).

Table 3.

Deltas (d = discharge – admission), effect size (standardized mean difference) for both groups of patients and P-value for between-group comparisons of differences.

Variable	“In-water” delta	“In-water” effect size	“On-land” delta	“On-land” effect size	P-value
d_BBS	11.1 ± 4.9	1.3	11.4 ± 6.9	1.4	0.86
d_DGI	5.8 ± 2.1	1.6	3.9 ± 3.2	0.8	0.04
d_NPS	−0.7 ± 0.7	−0.3	−0.5 ± 1.8	−0.2	0.58
d_ONLS	−0.2 ± 1.2	−0.2	−0.8 ± 0.9	−0.5	0.08
d_FIM	25.8 ± 8.2	2.5	26.1 ± 11.5	2.3	0.94
d_FAC	0.9 ± 0.6	1.6	1.4 ± 0.7	1.9	0.03
d_CONLEY	−1.5 ± 1.5	−1.2	−0.9 ± 1.4	−0.6	0.22
d_MRC hip flexors	0.5 ± 0.5	0.9	0.9 ± 0.5	1.7	0.01
d_MRC hip extensors	0.8 ± 0.4	0.6	0.8 ± 0.5	1.0	0.82
d_MRC ankle flexors	0.7 ± 0.7	1.3	0.9 ± 0.7	1.1	0.31
d_MRC ankle extensors	0.6 ± 0.7	0.6	0.9 ± 0.8	1.0	0.16

P-value: P-value for between-group comparison (unpaired t-test); BBS: Berg Balance Scale; DGI: Dynamic Gait Index; NPS: Neuropathic Pain Scale; ONLS: Overall Neuropathy Limitations Scale; FIM: Functional Independence Measure; FAC: Functional Ambulation Classification; MRC: Medical Research Council Scale.

Data are reported as mean ± SD.

Finally, we found that 21/21 and 18/19 patients experienced an improvement in BBS >3 in the “In-water” and “On-land” group, respectively (P = 0.29), and that 20/21 and 14/19 patients experienced an improvement in DGI >1.8 in the “In-water ”and “On-land” group, respectively (P = 0.06).

Discussion

In the present study, we showed that replacing three sessions per week of land-based physiotherapy with aquatic-based physiotherapy leads to similar gait and balance outcomes in the context of an intense rehabilitation program tailored for peripheral neuropathies. Even if limited by a small sample size, the importance of our result lays in being the first report about the effects of an aquatic training on neuropathic patients.

Indeed, peripheral neuropathies of different etiologies are quite common in the population. Gait, balance and painful disorders represent the main resulting disabilities and can highly compromise the autonomy in the activities of daily living.[21-23] Consequently, purpose of the rehabilitation is to maximize patients’ functions and to prolong an independent and safe locomotion using a goal-oriented treatment.[1] Most of the published studies regarded patients affected by diabetic neuropathy, who performed a minimum of two sessions/week of strengthening and/or balance exercises for at least six weeks.[4] The heterogeneity of those studies does not allow to draw definite conclusions, but while balance exercises seem to have good effect in non-metabolic neuropathies, metabolic disorders may benefit more from endurance training.[4] Although the literature lacks evidences about the effectiveness of an aquatic program on the symptoms and disabilities of patients affected by peripheral neuropathies, some studies revealed a good effect of aquatic therapy on gait and balance in other neurological diseases.[6-10]

In our study, the two groups were similar according to age, sex, number of patients with sensory impairment and with an acute peripheral neuropathy. Considering also the comparable rehabilitation program and the similar set of specific exercises, the only discriminating factor between the groups was the environment in which the specific training sessions were performed (water vs. land).

Taking into account the functional limitations affecting neuropathic patients, our training protocol was focused on the correction of balance and step abnormalities, in order to improve the safety of gait. For the same reason, we have chosen Berg Balance Scale and Dynamic Gait Index as primary outcomes, since they give a quantitative measure of static and dynamic balance and quality of gait. Both significantly improved in the two groups, as the secondary outcomes did: at the end of the intensive rehabilitation program, all patients showed a global gain in balance, gait and muscle strength. As exception, only “in-water” patients experienced a softening of neuropathic pain, in line with previous findings about the ability of warm water to relieve pain perception.[5]

When comparing the primary outcome measures, we found that the “in-water” group had a significantly better improvement in Dynamic Gait Index and a non-inferior improvement in Berg Balance Scale. Conversely, Functional Ambulation Classification improved to a wider extent in the “on-land” group. Hence, the effect of the rehabilitation on the stability and quality of gait tended to be higher for the “in-water” group, while the “on-land” tended to show a higher improvement of the walking independence.

Considering the small differences between the two groups and these contrasting results, we think that the main limitation of our study is the relatively small sample size. For the same reason, we were not able to perform subgroup analysis evaluating the effects of the two rehabilitative approaches according to the neuropathy etiology and timing and to the presence of sensorial dysfunction of the lower limbs, all factors that could alter the response to exercise. Moreover, we are aware that in the context of an intense rehabilitation program made by 3 hours of activity per day, the replacement of 3 hours per week of one-to-one land-based therapy with the same amount of one-to-one aquatic therapy would unlikely lead to a statistically and clinically significant difference in outcome over four weeks, except in the case of a very major effect. Last major weakness is the absence of follow-up data after the end of therapy that would be useful to understand possible outcome differences in the long term between the two rehabilitative approaches.

From our results, we conclude that there is no strong evidence for a significant contribution from aquatic therapy, when contrasted with the same time spent in on-land physiotherapy, to an intensive rehabilitative program tailored for patients affected by a peripheral neuropathy. Indeed, the aquatic environment in our study had a mild impact on increasing patients’ balance and gait but, on the other hand, the effect of aquatic therapy sessions was equivalent to the one obtained with the land-based ones.

Considering the high sense of stability that the water can provide and its effects on pain perception, we think that the water environment could be suitable mostly for the rehabilitation of those neuropathic patients with high fear of falling or pain. In these cases, aquatic therapy could be considered as an alternative strategy to the conventional physiotherapy, selectable according to the patients’ individual symptoms but still in need of further research.

Indeed, we think that the observed results represent a first description that would encourage the planning of larger clinical trials able to draw more definite conclusions about the best rehabilitation strategies for peripheral neuropathies.

Aquatic physiotherapy and on-land training have comparable effects on gait and balance in patients affected by peripheral neuropathies.

A larger trial is needed in order to evaluate a possible difference in the effectiveness of the two rehabilitative approaches.