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NeuroRehabilitation 36 (2015) 93–99 DOI:10.3233/NRE-141196 IOS Press
Robotic gait training improves motor skills and quality of life in hereditary spastic paraplegia F. Bertoluccia , S. Di Martinoa , D. Orsuccib , E. Caldarazzo Iencob , G. Sicilianob , B. Rossia , M. Mancusob and C. Chisaria,∗ a Neurorehabilitation b Neurology
Unit, University Hospital of Pisa, Pisa, Italy Unit, University Hospital of Pisa, Italy
Abstract. BACKGROUND: Gait impairment, balance problems and falls have a negative impact on independence in ADL and quality of life of patients affected by Hereditary Spastic Paraplegia (HSP). Since no pharmacological options are available, treatments rely mostly on rehabilitation therapy, although almost no data on this topic exist. Given the demonstrated effectiveness of robotics in improving gait and balance in various neurological diseases, aim of this study is to test the effectiveness of a robotic-aided program of gait training on balance, walking ability and quality of life in adult subjects affected by uncomplicated HSP. METHODS: Thirteen patients affected by uncomplicated HSP were subjected to a six-week robotic-aided gait training protocol. Participants underwent a battery of 3 walking test, 1 balance test and 2 quality of life questionnaires. RESULTS: At the end of the treatment a significant improvement of balance, walking ability and quality of life was observed in almost all the tests. The improvements were maintained over a two-month follow-up period. CONCLUSIONS: Our study indicates that a robotic gait training is long term effective in improving balance and walking ability with a positive impact on quality of life in patients affected by uncomplicated form of HSP. As currently there is no specific treatment to prevent or reverse HSP progression, our contribution would be significant for the development of exercise recommendations in this rare disease. Keywords: Hereditary Spastic Paraplegia, gait rehabilitation, balance, robotics
1. Introduction Hereditary Spastic Paraplegia (HSP) comprises a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by gait disturbance owing to spasticity and weakness of the lower limbs, due to corticospinal tract and dorsal column ∗ Address
for correspondence: Carmelo Chisari, Neurorehabilitation Unit, University Hospital of Pisa, Via Paradisa 2, 56126 Pisa, Italy. Tel.: +39 050 996907; E-mail: [email protected].
degeneration (Fink 2003). HSP is a rare disease with a prevalence of 2–10:100,000 (Brignolio 1986, Polo 1991, Orsucci et al, 2014). The genetics of HSP are complex: all modes of inheritance (autosomal dominant, autosomal recessive, and X-linked recessive) have been described (Harding 1993, Fink 2003) and more than 50 loci (SPG1 – SPG57) have been identified so far (Salinas 2008). Traditionally HSP has been classified into uncomplicated (“pure”) and complicated form, depending on the presence of other neurological features in addition to spastic paraparesis (Harding 1993,
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F. Bertolucci et al. / Robotic gait training in HSP
Fink 2003). The cardinal abnormalities on examination of patients with uncomplicated HSP include spasticity, hyperreflexia and extensor plantar responses, with weakness of a pyramidal distribution in the lower limbs. The lower limb spasticity is the prominent finding on examination, particularly in the hamstrings, quadriceps, and ankles. This pattern of hypertonia is responsible for the classic gait with the affected person demonstrating circumduction and toe walking (Mc Dermott 2000). At present, there is no specific cure to prevent or reverse nerve degeneration in HSP and treatments are directed at reducing symptoms (Fink 2003); current recommendations include physical therapy directed toward improving cardiovascular fitness, maintaining and improving muscle strength and gait, prescription of orthotics and administration of drugs to reduce muscle spasticity (Fink 2003, Hecht 2008), without specific guidance on what is the most suitable management protocol in these patients. Nevertheless, abnormal gait and balance impairment due to weakness and increased tone of the lower limbs are symptoms that impact very negatively on the capability of working and independent living of individuals affected by HSP, who frequently fall (Fink 2003, Martin 2014) with risk of potentially severe injuries. Furthermore, the severity of the disease impact very negatively on their quality of life, which seems to be closely related to the loss of walking ability (Klimpe et al. 2012, Grose 2013). On this background the contribution of rehabilitation would seem crucial in the long-term management of these patients. However, surprisingly, there is an almost complete lack of literature regarding the role of rehabilitation in HSP. Only one recent study proposed a rehabilitative treatment, in a group of 9 HSP patients, consisting of hydrotherapy, without taking into account functional data as outcome measures (Zhang 2014). Nevertheless, as lower limbs spasticity in HSP patients determines primarily balance and gait impairment, rehabilitation programs should address these issues at any stage of the disease, focusing specifically on those aspects which impact negatively on patients’ quality of life. Currently, in the broad range of intervention offered by modern neurorehabilitation, new robotic locomotion systems have been developed for facilitation of gait training in different neurological disorders. One of these devices, the Lokomat, has been commercially available for several years. The Lokomat (Hocoma AG, Volketswil, Switzerland) is a robotic gait orthosis combined with a harness-supported body weight
system that combines new technology with the recognized advantages of treadmill training eg, optimal loading, adequate sensory input, optimal hip extension, interlimb coordination, task-specific locomotion movements, and early initiation and prolonged training sessions (Colombo 2000, Neckel 2008). Although a set of data does not support a clear benefit of robotic gait training when compared with therapist-assisted one (Hidler 2005, Hornby 2008), several publications (Westlake 2009, Mayr 2007, Chisari 2014) emphasize that automatized gait training may be at least as effective as manually assisted treadmill training in improving motor impairment, balance and walking ability. Aim of this study is to test the effectiveness of a robotic-aided intensive program of gait training on balance, walking ability and quality of life in adult subjects affected by uncomplicated HSP.
2. Materials and methods We recruited 13 patients (7 female and 6 male, 31–62 years of age, mean age 46.3 ± 8.9) affected by uncomplicated HSP (see Table 1 for details). Inclusion criteria were: (i) age between 18 and 70 years of age; (ii) genetic diagnosis of HSP; (iii) ability to walk independently for 6 minutes, with or without walking aids. Exclusion criteria were: (i) other concurring neurological disorders; (ii) age under 18 or over 70; (iii) recent orthopaedic intervention at the lower limbs; (iv) concurring pathologies limiting ambulation; (v) unstable cardiopulmonary condition; (vi) severe hypertension, pressure sores, severe osteoporosis. Table 1 Patients’ clinical and genetic features. pt = patient. SPRS = Spastic Paraplegia Rating Scale Pt
Sex
Age
Genetics
SPRS
Ageatonset
1 2 3 4 5 6 7 8 9 10 11 12 13
F F F F F M M M F F M M M
51 41 57 31 48 50 38 62 37 50 54 39 44
SPG4 SPG4 SPG7 SPG11 SPG4 SPG7 SPG7 SPG7 SPG5 SPG4 SPG7 SPG7 SPG4
10 4 9 2 3 6 14 1 31 22 21 6 6
10 12 35 28 48 49 27 53 24 30 46 10 42
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2.1. Study design All patients underwent a rehabilitative treatment provided by Lokomat, accounting for three weekly sessions, for a six weeks long period. An experienced physician started the therapeutic session imposing the maximum assistance of the robot (100% force guidance) on both legs, the maximum comfortable speed for the patient, and a body weight support (BWS) of 40%. Then, according to the patient’s muscle tone and gait quality (i.e., adequate knee control during the stance phase, symmetry of the steps, absence of knee buckling and toe drag), monitored by a visual feedback supplied by the machine, the therapist gradually reduced the guidance force on both legs, without dropping below 75%. Moreover, along the treatment, the exercises were modified in term of duration, covered distance and speed in order to increase workload, maximize efforts for the patient and challenge his/her adaptation to the training. 2.2. Outcome measures Outcome measures were assessed the week prior the treatment initiation (T0), at the end (T1) and after a twomonth-follow-up. In particular, we have assessed: (i) Berg Balance Scale (BBS), a scale of ability to maintain balance, either statically or while performing functional movements. It comprises 14 observable tasks common to everyday life measured on a 5 point ordinal scale (Bronstein, 2013); (ii) Timed Up and Go Test (TUG): in this test subjects are asked to stand up from a chair, walk for 3 meters, walk back and sit down again, while the time necessary to complete the exercise is recorded (Schoene, 2013); (iii) 10-Meter Walking Test (10mWT): for this test, participants must ambulate 10 meters while being timed so that their walking speed may be calculated. A “flying start” is used where the subject may accelerate 2 meters before entering the timed 10-meter distance and 2 meters to decelerate afterwards. Speed is only calculated for the 10-meter distance between the “end zones” (Morganti, 2005); (iv) Six-minute walk test (6MWT): subjects were instructed to “walk as far as possible in six minutes”. Subjects walked up and down a 25 m walkway without encouragement (Dalgas, 2013). The time taken to complete the test was recorded and the speed of walking was calculated. The heart rate was measured before and after the exercise in order to calculate the Physiological Cost Index (PCI); (v) Physiological Cost Index (PCI): the PCI corresponds to the increase in heart rate per meter walked by the subject. This index provides an estimate of the oxygen consump-
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tion following the execution of submaximal exercise. This index is obtained by the following equation: (HR2 – HR1)/walking speed, were HR1 and HR2 correspond to the heart rate recorded before and after performing the 6MWT respectively (Mac Gregor, 1981); (vi) Short Form 36 (SF-36): it is an assessment tool of quality of life (QoL). Is a 36-item scale divided in two domain: Physical component subscale and Mental component subscale, each ranging from 0 to 100 (Hobart, 2001a); (vii) Hospital Anxiety and Depression Scale (HADS): it is one of the most widely used instruments to rapidly measure psychological status in patient as well as nonpatient populations. It includes 14 questions (7 items per subscale) that each question is scored from 0 to 3 and the final score for each subscale ranges from 0 to 21. According to studies, grades 8 and higher is indicative for the relating subtest disorder (Bjelland 2002); (viii) Modified Ashworth Scale (MAS): it is probably the most used instrument to clinically assess spasticity (Bohannon 1987). In this study we used MAS to evaluate spasticity of lower limbs. Protocol was designed in accordance with the Local Ethics Committee. After a careful explanation of the procedures, informed consent was obtained from all the subjects. Data were examined before (T0), after the treatment (T1) and two months after the end of the treatment. The non-parametric Wilcoxon signed-rank test was applied. Significance of statistical tests was set at p < 0.05.
3. Results (These are described as (mean value ± standard deviation); p values are described in the figures.) At the end of the treatment (T1) a statistically significant improvement of the BBS (46.8 ± 10.7 at T0 vs 50.5 ± 9.6 at T1), of the 10mWT (13.3 ± 9.9 sec at T0 vs 11.8 ± 8.9 sec at T1) and of the 6MWT (323.8 ± 118.0 m at T0 vs 365.7 ± 122.1 m at T1) was observed, while the PCI remained unmodified (0.26 ± 0.35 at T0 vs 0.31 ± 0.67 at T1) (Figs. 1 and 2). The TUG showed an improvement close to significance (12.9 ± 9.3 sec at T0 vs 12.3 ± 8.0 sec at T1 (Fig. 2). We didn’t observe any modification of muscle tone according to the MAS. The SF-36 showed a significant improvement in the domains of Physical Role (55.8 ± 39.7 at T0 vs 78.8 ± 37.9 at T1), Social Function (66.2 ± 24.5 at T0 vs 79.5 ± 18.2 at T1), Emotional Role (66.3 ± 30.5 at T0 vs 79.4 ± 37.4 at T1), and Mental Health (67.4 ± 20.4 at T0 vs
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T0
T0
T1
T1
T0 T1
Fig. 1. A: Ten meters walking test (10mWT) before (T0) and after (T1) the treatment (p = 0.002); B: Timed up and Go (TUG), before (T0) and after (T1) the treatment (p = 0.060); C: Berg Balance Scale (BBS) before (T0) and after (T1) the treatment (p = 0.003).
Fig. 2. A: Six minute walking test (6MWT), before (T0) and after (T1) the treatment (p = 0,001); B: Physiological Cost Index (PCI), before (T0) and after (T1) the treatment.
74.5 ± 23.3 at T1), as shown in Table 2. The HADS showed a significant decrease of anxiety (5.6 ± 4.8 at T0 vs 3.7 ± 4.9 at T1) and a slight decrease of depression (6.2 ± 4.9 at T0 vs 4.8 ± 5.4 at T1), as shown in Fig. 3. The two-month follow-up didn’t show any variation with respect to T1 either in the functional tests or in the psychological scales.
4. Discussion Despite the fact that rehabilitation seems to be the only therapeutic option in the long-term management of HSP, except for the pharmacological treatment of spasticity, there is a nearly complete lack of literature about this issue. Based on previous literature describing
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Table 2 Short form-36 (SF-36), before (T0) and after (T1) the treatment. Pt = patient Short Form SF-36 Pt 1 2 3 4 5 6 7 8 9 10 11 12 13
T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1
Physical Function
Physical Role
Bodily Pain
General Health
Vitality
Social Function
Emotional Role
Mental Health
30 60 80 65 30 65 85 95 85 90 40 55 45 60 65 70 25 25 45 25 25 50 100 100 85 85
0 100 0 0 25 50 100 100 100 100 50 100 75 100 50 75 75 100 100 100 0 0 100 100 50 100
51 100 72 32 41 61 100 100 41 80 84 74 100 51 100 100 100 100 32 41 100 64 100 100 100 100
32 52 20 0 45 61 61 82 61 55 61 37 35 56 76 32 60 45 25 25 25 37 97 35 67 61
50 70 15 15 30 85 85 75 70 80 75 75 20 45 75 60 35 60 65 75 40 35 65 75 85 85
50 87 25 50 50 87 87 100 87 100 87 62 25 62 75 75 50 50 62 62 75 62 87 100 100 100
66 100 33 0 33 100 100 100 66 100 100 100 66 100 66 66 100 66 66 0 0 100 100 100 100 100
84 84 16 12 56 64 64 88 88 92 72 72 68 92 72 60 56 84 76 80 48 52 92 96 84 92
Fig. 3. Hospital Anxiety and Depression Scale (HADS); A: anxiety domain before (T0) and after (T1) the treatment (p = 0,0020); B: depression domain before (T0) and after (T1) the treatment. Patient number nine did not support this test because of the presence of language barrier.
the positive effect of robotic gait training on balance and walking ability in different neurologic conditions (Mayr 2007, Chisari 2014), we hypothesized that an intensive robotic-aided gait rehabilitation protocol would be effective in reducing these disabling impairments in a group of patients affected by uncomplicated HSP, with a positive impact on quality of life and psychological status. Our results showed a clear-cut improvement of balance, walking speed and endurance at the end of
the treatment. These data were accompanied by an improvement of patients’ psychological status with a consistent positive influence on quality of life. Furthermore, a two-months-follow-up showed that these improvements were maintained over time. Despite the exiguity of our sample and the lack of a control group, we believe that these data have to be taken into account for further investigations in the field, considering the rarity of the disease and the fact that no larger groups of patients have been studied before.
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In fact, we found only one study proposing rehabilitative treatment in HSP patients: in this study nine HSP patients were subjected to a 10-week hydrotherapy programme, and the effect of the treatment was assessed only by means of 3D gait analysis. The authors observed that participants had increased walking speed and step length but also that hydrotherapy mainly increased the ability to perform compensatory strategies rather than resulting in a more typical kinematic and kinetic approach (Zhang 2014). Nevertheless, as lower limbs spasticity in HSP patients determines primarily balance and gait disorders with an augmented risk of falls (Fink 2000, Thurman 2008, Martin 2014), it is our belief that rehabilitation programs should address these issues at any stage of the disease and therefore that functional tests should be utilized as outcome measures. The prevalence of falls among neurological patients is unknown, although disturbances of gait and posture are common. A study of Stolze et al (2004) assessed that falls in neurological patients are particularly linked to disorders affecting gait and balance. HSP patients fall frequently and it has been hypothesized that delayed postural responses contribute to their balance impairments (Nonnekes 2013). In our study a significant improvement of balance, as assessed by the BBS, was observed. While the relationship between this scale and fall risk is known, it must be considered that also poor performances in the 6mWT and the 10MWT are related to a higher risk of falling (Sosnoff, 2011a, 2011b, Nilsag˚ard, 2009). Our data showed a significant improvement in all of these walking tests at the end of the protocol. So, such a rehabilitative treatment could have a positive impact on this important aspect. Moreover the treatment did not worsen lower limbs spasticity; this is an important issue that underlines the safety of the treatment: in fact, the risk that lies in subjecting these patients to physical activity not comprising muscle stretching is that of increasing muscle tone. Our patients did not experience this side effect, and this is a remarkable datum as it is also known that lower limbs spasticity is an indicator of risk of falling (Soyuer 2007, Martin 2014). The most valuable data come from the analysis of quality of life scales; the treatment also had a relevant positive impact on patients’ quality of life and psychological status. The Short-Form 36 showed a significant improvement in the domains of Physical Role, Emotional Role, Social Function and Mental Health. The Hospital Anxiety scale showed a clear-cut improvement in the hanxiety domain. Little is known about the psychosocial impact of disease and Health-Related Quality
of Life (HRQoL) in patients with HSP; it is known that subjective perception of well-being is worse then in healthy subjects, and a more severe affection of physical aspects of quality of life compared to mental aspects is documented. It is also known that subjective perception of well-being is closely related to disease severity, especially to walking ability (Klimpe 2012, Braschinsky 2011) and therefore that QoL is significantly affected by ADL indipendence (Takemasa 2014). For these reasons rehabilitation programs should focus on improving patients’ indipendence in ADL and individual’s perception of well-being is an important fac-tor that should be considered with regards to chronically ill and disabled patients (Swanson 1993). Previous studies enrolling HSP patients assess that HRQoL is a valid parameter in HSP that should be considered in upcoming therapeutical trials (Klimpe 2012), and therefore it is important to highlight the impact of the innovative rehabilitation protocol proposed in this study on HSP patients’ subjective well-being. 5. Conclusion Our study indicates that a robotic gait training is long term effective in improving balance and walking ability with a positive impact on quality of life in patients affected by uncomplicated form of HSP. As currently there is no specific treatment to prevent or reverse HSP progression, our contribution would be significant for the development of exercise recommendations in this rare disease. Declaration of interest I declare that each author participated sufficiently in the work to take public responsibility for the content. I affirm that I had access to all data from the study, both what is reported and what is unreported, and also that I had complete freedom to direct its analysis and its reporting, without influence from sponsors. I also affirm that there was no editorial direction or censorship from the sponsors. No part of this work has been published. No conflict of interest exists. References Bjelland, I., Dahl, A. A., Haug, T. T., & Neckelmann, D. (2002). The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J Psychosom Res, 52, 69-77.
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limb spasticity in adults: A systematic review. Neuropsychiatr Dis Treat, 10, 111-122. Mayr, A., Kofler, M., Quirbach, E., Matzak, H., Frohlich, K., Saltuari, L. (2007). Prospective, blinded, randomized crossover study of gait rehabilitation in stroke patients using the Lokomat gait orthosis. Neurorehabilitation and neural repair, 21 (4), 307-314. McDermott, C., White, K., Bushby, K., & Shaw, P. (2000). Hereditary spastic paraparesis: A review of new developments. J Neurol Neurosurg Psychiatry, 69(2), 150-160. Morganti, B., Scivoletto, G., Ditunno, P., Ditunno, J., Molinari, M. (2005). Walking index for spinal cord injury (WISCI): Criterion validation. Spinal Cord, 43(1), 27-33. 33. Neckel, N. D., Blonien, N., Diane Nichols, D., & Hidler, J. (2008). Abnormal joint torque patterns exhibited by chronic stroke subjects while walking with a prescribed physiological gait pattern. Journal of NeuroEngineering and Rehabilitation, 5, 19. Nonnekes, J., de Niet, M., Oude Nijhuis, L. B., de Bot, S. T., van de Warrenburg, B. P., Bloem, B. R., Geurts, A. C., Weerdesteyn, V. (2013). Mechanisms of postural instability in hereditary spastic paraplegia. J Neurol, 260(9), 2387-2395. Epub 2013 Jun 20. Orsucci, D., Petrucci, L., Ienco, E.C., Chico, L., Simi, P., Fogli, A., Baldinotti, F., Simoncini, C., Logerfo, A., Carlesi, C., Arnoldi, A., Bassi, M.T., Siciliano, G., Bonuccelli, U., & Mancuso, M. (2014). Hereditary spastic paraparesis in adults. A clinical and genetic perspective from Tuscany. Clin Neurol Neurosurg, 120, 14-19. Polo, J. M., Calleja, J., Combarros, O., Berciano, J. (1991). Hereditary ataxias and paraplegias in Cantabria Spain. An epidemiological and clinical study. Brain, 114(Pt 2), 855-866. Salinas, S., Proukakis, C., Crosby, A., Warner, T. T. (2008). Hereditary spastic paraplegia: Clinical features and pathogenetic mechanisms. Lancet Neurol, 7(12), 1127-1138. Schoene, D., Wu, S. M., Mikolaizak, A. S., Menant, J. C., Smith, S. T., Delbaere, K., & Lord, S. R. (2013). Discriminative ability and predictive validity of the timed up and go test in identifying older people who fall: Systematic review and meta-analysis. J Am Geriatr Soc, 61(2), 202-208. Soyuer, F., & Ozt¨urk, A. (2007). The effect of spasticity, sense and walking aids in falls of people after chronic stroke. Disabil Rehabil, 29(9), 679-687. Stolze, H1., Klebe, S., Zechlin, C., Baecker, C., Friege, L., & Deuschl, G. (2004). Falls in frequent neurological diseases–prevalence, risk factors and aetiology. J Neurol, 251(1), 79-84. Swanson, K. M. (1993). Nursing as informed caring for the well-being of others. Image J Nurs Sch, 25, 352-357. Takemasa, S., Nakagoshi, R., Murakami, M., Uesugi, M., Inoue, Y., Gotou, M., Koeda, H., Naruse, S. (2014). Factors affecting quality of life of the homebound elderly hemiparetic stroke patients. J Phys Ther Sci, 26(2), 301-303. doi: 10.1589/jpts.26.301. Epub 2014 Feb 28. Westlake, K. P., & Patten, C. (2009). Pilot study of Lokomat versus manual-assisted treadmill training for locomotor recovery post-stroke. Journal of Neuroengineering and Rehabilitation, 6, 18. Zhang, Y., Roxburgh, R., Huang, L., Parsons, J., Davies, T. C. (2014). The effect of hydrotherapy treatment on gait characteristics of hereditary spastic paraparesis patients. Gait Posture, 39(4), 10749. doi: 10.1016/j.gaitpost.2014.01.010. Epub 2014 Jan 29.
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NeuroRehabilitation 36 (2015) 93–99 DOI:10.3233/NRE-141196 IOS Press
Robotic gait training improves motor skills and quality of life in hereditary spastic paraplegia F. Bertoluccia , S. Di Martinoa , D. Orsuccib , E. Caldarazzo Iencob , G. Sicilianob , B. Rossia , M. Mancusob and C. Chisaria,∗ a Neurorehabilitation b Neurology
Unit, University Hospital of Pisa, Pisa, Italy Unit, University Hospital of Pisa, Italy
Abstract. BACKGROUND: Gait impairment, balance problems and falls have a negative impact on independence in ADL and quality of life of patients affected by Hereditary Spastic Paraplegia (HSP). Since no pharmacological options are available, treatments rely mostly on rehabilitation therapy, although almost no data on this topic exist. Given the demonstrated effectiveness of robotics in improving gait and balance in various neurological diseases, aim of this study is to test the effectiveness of a robotic-aided program of gait training on balance, walking ability and quality of life in adult subjects affected by uncomplicated HSP. METHODS: Thirteen patients affected by uncomplicated HSP were subjected to a six-week robotic-aided gait training protocol. Participants underwent a battery of 3 walking test, 1 balance test and 2 quality of life questionnaires. RESULTS: At the end of the treatment a significant improvement of balance, walking ability and quality of life was observed in almost all the tests. The improvements were maintained over a two-month follow-up period. CONCLUSIONS: Our study indicates that a robotic gait training is long term effective in improving balance and walking ability with a positive impact on quality of life in patients affected by uncomplicated form of HSP. As currently there is no specific treatment to prevent or reverse HSP progression, our contribution would be significant for the development of exercise recommendations in this rare disease. Keywords: Hereditary Spastic Paraplegia, gait rehabilitation, balance, robotics
1. Introduction Hereditary Spastic Paraplegia (HSP) comprises a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by gait disturbance owing to spasticity and weakness of the lower limbs, due to corticospinal tract and dorsal column ∗ Address
for correspondence: Carmelo Chisari, Neurorehabilitation Unit, University Hospital of Pisa, Via Paradisa 2, 56126 Pisa, Italy. Tel.: +39 050 996907; E-mail: [email protected].
degeneration (Fink 2003). HSP is a rare disease with a prevalence of 2–10:100,000 (Brignolio 1986, Polo 1991, Orsucci et al, 2014). The genetics of HSP are complex: all modes of inheritance (autosomal dominant, autosomal recessive, and X-linked recessive) have been described (Harding 1993, Fink 2003) and more than 50 loci (SPG1 – SPG57) have been identified so far (Salinas 2008). Traditionally HSP has been classified into uncomplicated (“pure”) and complicated form, depending on the presence of other neurological features in addition to spastic paraparesis (Harding 1993,
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F. Bertolucci et al. / Robotic gait training in HSP
Fink 2003). The cardinal abnormalities on examination of patients with uncomplicated HSP include spasticity, hyperreflexia and extensor plantar responses, with weakness of a pyramidal distribution in the lower limbs. The lower limb spasticity is the prominent finding on examination, particularly in the hamstrings, quadriceps, and ankles. This pattern of hypertonia is responsible for the classic gait with the affected person demonstrating circumduction and toe walking (Mc Dermott 2000). At present, there is no specific cure to prevent or reverse nerve degeneration in HSP and treatments are directed at reducing symptoms (Fink 2003); current recommendations include physical therapy directed toward improving cardiovascular fitness, maintaining and improving muscle strength and gait, prescription of orthotics and administration of drugs to reduce muscle spasticity (Fink 2003, Hecht 2008), without specific guidance on what is the most suitable management protocol in these patients. Nevertheless, abnormal gait and balance impairment due to weakness and increased tone of the lower limbs are symptoms that impact very negatively on the capability of working and independent living of individuals affected by HSP, who frequently fall (Fink 2003, Martin 2014) with risk of potentially severe injuries. Furthermore, the severity of the disease impact very negatively on their quality of life, which seems to be closely related to the loss of walking ability (Klimpe et al. 2012, Grose 2013). On this background the contribution of rehabilitation would seem crucial in the long-term management of these patients. However, surprisingly, there is an almost complete lack of literature regarding the role of rehabilitation in HSP. Only one recent study proposed a rehabilitative treatment, in a group of 9 HSP patients, consisting of hydrotherapy, without taking into account functional data as outcome measures (Zhang 2014). Nevertheless, as lower limbs spasticity in HSP patients determines primarily balance and gait impairment, rehabilitation programs should address these issues at any stage of the disease, focusing specifically on those aspects which impact negatively on patients’ quality of life. Currently, in the broad range of intervention offered by modern neurorehabilitation, new robotic locomotion systems have been developed for facilitation of gait training in different neurological disorders. One of these devices, the Lokomat, has been commercially available for several years. The Lokomat (Hocoma AG, Volketswil, Switzerland) is a robotic gait orthosis combined with a harness-supported body weight
system that combines new technology with the recognized advantages of treadmill training eg, optimal loading, adequate sensory input, optimal hip extension, interlimb coordination, task-specific locomotion movements, and early initiation and prolonged training sessions (Colombo 2000, Neckel 2008). Although a set of data does not support a clear benefit of robotic gait training when compared with therapist-assisted one (Hidler 2005, Hornby 2008), several publications (Westlake 2009, Mayr 2007, Chisari 2014) emphasize that automatized gait training may be at least as effective as manually assisted treadmill training in improving motor impairment, balance and walking ability. Aim of this study is to test the effectiveness of a robotic-aided intensive program of gait training on balance, walking ability and quality of life in adult subjects affected by uncomplicated HSP.
2. Materials and methods We recruited 13 patients (7 female and 6 male, 31–62 years of age, mean age 46.3 ± 8.9) affected by uncomplicated HSP (see Table 1 for details). Inclusion criteria were: (i) age between 18 and 70 years of age; (ii) genetic diagnosis of HSP; (iii) ability to walk independently for 6 minutes, with or without walking aids. Exclusion criteria were: (i) other concurring neurological disorders; (ii) age under 18 or over 70; (iii) recent orthopaedic intervention at the lower limbs; (iv) concurring pathologies limiting ambulation; (v) unstable cardiopulmonary condition; (vi) severe hypertension, pressure sores, severe osteoporosis. Table 1 Patients’ clinical and genetic features. pt = patient. SPRS = Spastic Paraplegia Rating Scale Pt
Sex
Age
Genetics
SPRS
Ageatonset
1 2 3 4 5 6 7 8 9 10 11 12 13
F F F F F M M M F F M M M
51 41 57 31 48 50 38 62 37 50 54 39 44
SPG4 SPG4 SPG7 SPG11 SPG4 SPG7 SPG7 SPG7 SPG5 SPG4 SPG7 SPG7 SPG4
10 4 9 2 3 6 14 1 31 22 21 6 6
10 12 35 28 48 49 27 53 24 30 46 10 42
F. Bertolucci et al. / Robotic gait training in HSP
2.1. Study design All patients underwent a rehabilitative treatment provided by Lokomat, accounting for three weekly sessions, for a six weeks long period. An experienced physician started the therapeutic session imposing the maximum assistance of the robot (100% force guidance) on both legs, the maximum comfortable speed for the patient, and a body weight support (BWS) of 40%. Then, according to the patient’s muscle tone and gait quality (i.e., adequate knee control during the stance phase, symmetry of the steps, absence of knee buckling and toe drag), monitored by a visual feedback supplied by the machine, the therapist gradually reduced the guidance force on both legs, without dropping below 75%. Moreover, along the treatment, the exercises were modified in term of duration, covered distance and speed in order to increase workload, maximize efforts for the patient and challenge his/her adaptation to the training. 2.2. Outcome measures Outcome measures were assessed the week prior the treatment initiation (T0), at the end (T1) and after a twomonth-follow-up. In particular, we have assessed: (i) Berg Balance Scale (BBS), a scale of ability to maintain balance, either statically or while performing functional movements. It comprises 14 observable tasks common to everyday life measured on a 5 point ordinal scale (Bronstein, 2013); (ii) Timed Up and Go Test (TUG): in this test subjects are asked to stand up from a chair, walk for 3 meters, walk back and sit down again, while the time necessary to complete the exercise is recorded (Schoene, 2013); (iii) 10-Meter Walking Test (10mWT): for this test, participants must ambulate 10 meters while being timed so that their walking speed may be calculated. A “flying start” is used where the subject may accelerate 2 meters before entering the timed 10-meter distance and 2 meters to decelerate afterwards. Speed is only calculated for the 10-meter distance between the “end zones” (Morganti, 2005); (iv) Six-minute walk test (6MWT): subjects were instructed to “walk as far as possible in six minutes”. Subjects walked up and down a 25 m walkway without encouragement (Dalgas, 2013). The time taken to complete the test was recorded and the speed of walking was calculated. The heart rate was measured before and after the exercise in order to calculate the Physiological Cost Index (PCI); (v) Physiological Cost Index (PCI): the PCI corresponds to the increase in heart rate per meter walked by the subject. This index provides an estimate of the oxygen consump-
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tion following the execution of submaximal exercise. This index is obtained by the following equation: (HR2 – HR1)/walking speed, were HR1 and HR2 correspond to the heart rate recorded before and after performing the 6MWT respectively (Mac Gregor, 1981); (vi) Short Form 36 (SF-36): it is an assessment tool of quality of life (QoL). Is a 36-item scale divided in two domain: Physical component subscale and Mental component subscale, each ranging from 0 to 100 (Hobart, 2001a); (vii) Hospital Anxiety and Depression Scale (HADS): it is one of the most widely used instruments to rapidly measure psychological status in patient as well as nonpatient populations. It includes 14 questions (7 items per subscale) that each question is scored from 0 to 3 and the final score for each subscale ranges from 0 to 21. According to studies, grades 8 and higher is indicative for the relating subtest disorder (Bjelland 2002); (viii) Modified Ashworth Scale (MAS): it is probably the most used instrument to clinically assess spasticity (Bohannon 1987). In this study we used MAS to evaluate spasticity of lower limbs. Protocol was designed in accordance with the Local Ethics Committee. After a careful explanation of the procedures, informed consent was obtained from all the subjects. Data were examined before (T0), after the treatment (T1) and two months after the end of the treatment. The non-parametric Wilcoxon signed-rank test was applied. Significance of statistical tests was set at p < 0.05.
3. Results (These are described as (mean value ± standard deviation); p values are described in the figures.) At the end of the treatment (T1) a statistically significant improvement of the BBS (46.8 ± 10.7 at T0 vs 50.5 ± 9.6 at T1), of the 10mWT (13.3 ± 9.9 sec at T0 vs 11.8 ± 8.9 sec at T1) and of the 6MWT (323.8 ± 118.0 m at T0 vs 365.7 ± 122.1 m at T1) was observed, while the PCI remained unmodified (0.26 ± 0.35 at T0 vs 0.31 ± 0.67 at T1) (Figs. 1 and 2). The TUG showed an improvement close to significance (12.9 ± 9.3 sec at T0 vs 12.3 ± 8.0 sec at T1 (Fig. 2). We didn’t observe any modification of muscle tone according to the MAS. The SF-36 showed a significant improvement in the domains of Physical Role (55.8 ± 39.7 at T0 vs 78.8 ± 37.9 at T1), Social Function (66.2 ± 24.5 at T0 vs 79.5 ± 18.2 at T1), Emotional Role (66.3 ± 30.5 at T0 vs 79.4 ± 37.4 at T1), and Mental Health (67.4 ± 20.4 at T0 vs
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F. Bertolucci et al. / Robotic gait training in HSP
T0
T0
T1
T1
T0 T1
Fig. 1. A: Ten meters walking test (10mWT) before (T0) and after (T1) the treatment (p = 0.002); B: Timed up and Go (TUG), before (T0) and after (T1) the treatment (p = 0.060); C: Berg Balance Scale (BBS) before (T0) and after (T1) the treatment (p = 0.003).
Fig. 2. A: Six minute walking test (6MWT), before (T0) and after (T1) the treatment (p = 0,001); B: Physiological Cost Index (PCI), before (T0) and after (T1) the treatment.
74.5 ± 23.3 at T1), as shown in Table 2. The HADS showed a significant decrease of anxiety (5.6 ± 4.8 at T0 vs 3.7 ± 4.9 at T1) and a slight decrease of depression (6.2 ± 4.9 at T0 vs 4.8 ± 5.4 at T1), as shown in Fig. 3. The two-month follow-up didn’t show any variation with respect to T1 either in the functional tests or in the psychological scales.
4. Discussion Despite the fact that rehabilitation seems to be the only therapeutic option in the long-term management of HSP, except for the pharmacological treatment of spasticity, there is a nearly complete lack of literature about this issue. Based on previous literature describing
F. Bertolucci et al. / Robotic gait training in HSP
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Table 2 Short form-36 (SF-36), before (T0) and after (T1) the treatment. Pt = patient Short Form SF-36 Pt 1 2 3 4 5 6 7 8 9 10 11 12 13
T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1
Physical Function
Physical Role
Bodily Pain
General Health
Vitality
Social Function
Emotional Role
Mental Health
30 60 80 65 30 65 85 95 85 90 40 55 45 60 65 70 25 25 45 25 25 50 100 100 85 85
0 100 0 0 25 50 100 100 100 100 50 100 75 100 50 75 75 100 100 100 0 0 100 100 50 100
51 100 72 32 41 61 100 100 41 80 84 74 100 51 100 100 100 100 32 41 100 64 100 100 100 100
32 52 20 0 45 61 61 82 61 55 61 37 35 56 76 32 60 45 25 25 25 37 97 35 67 61
50 70 15 15 30 85 85 75 70 80 75 75 20 45 75 60 35 60 65 75 40 35 65 75 85 85
50 87 25 50 50 87 87 100 87 100 87 62 25 62 75 75 50 50 62 62 75 62 87 100 100 100
66 100 33 0 33 100 100 100 66 100 100 100 66 100 66 66 100 66 66 0 0 100 100 100 100 100
84 84 16 12 56 64 64 88 88 92 72 72 68 92 72 60 56 84 76 80 48 52 92 96 84 92
Fig. 3. Hospital Anxiety and Depression Scale (HADS); A: anxiety domain before (T0) and after (T1) the treatment (p = 0,0020); B: depression domain before (T0) and after (T1) the treatment. Patient number nine did not support this test because of the presence of language barrier.
the positive effect of robotic gait training on balance and walking ability in different neurologic conditions (Mayr 2007, Chisari 2014), we hypothesized that an intensive robotic-aided gait rehabilitation protocol would be effective in reducing these disabling impairments in a group of patients affected by uncomplicated HSP, with a positive impact on quality of life and psychological status. Our results showed a clear-cut improvement of balance, walking speed and endurance at the end of
the treatment. These data were accompanied by an improvement of patients’ psychological status with a consistent positive influence on quality of life. Furthermore, a two-months-follow-up showed that these improvements were maintained over time. Despite the exiguity of our sample and the lack of a control group, we believe that these data have to be taken into account for further investigations in the field, considering the rarity of the disease and the fact that no larger groups of patients have been studied before.
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F. Bertolucci et al. / Robotic gait training in HSP
In fact, we found only one study proposing rehabilitative treatment in HSP patients: in this study nine HSP patients were subjected to a 10-week hydrotherapy programme, and the effect of the treatment was assessed only by means of 3D gait analysis. The authors observed that participants had increased walking speed and step length but also that hydrotherapy mainly increased the ability to perform compensatory strategies rather than resulting in a more typical kinematic and kinetic approach (Zhang 2014). Nevertheless, as lower limbs spasticity in HSP patients determines primarily balance and gait disorders with an augmented risk of falls (Fink 2000, Thurman 2008, Martin 2014), it is our belief that rehabilitation programs should address these issues at any stage of the disease and therefore that functional tests should be utilized as outcome measures. The prevalence of falls among neurological patients is unknown, although disturbances of gait and posture are common. A study of Stolze et al (2004) assessed that falls in neurological patients are particularly linked to disorders affecting gait and balance. HSP patients fall frequently and it has been hypothesized that delayed postural responses contribute to their balance impairments (Nonnekes 2013). In our study a significant improvement of balance, as assessed by the BBS, was observed. While the relationship between this scale and fall risk is known, it must be considered that also poor performances in the 6mWT and the 10MWT are related to a higher risk of falling (Sosnoff, 2011a, 2011b, Nilsag˚ard, 2009). Our data showed a significant improvement in all of these walking tests at the end of the protocol. So, such a rehabilitative treatment could have a positive impact on this important aspect. Moreover the treatment did not worsen lower limbs spasticity; this is an important issue that underlines the safety of the treatment: in fact, the risk that lies in subjecting these patients to physical activity not comprising muscle stretching is that of increasing muscle tone. Our patients did not experience this side effect, and this is a remarkable datum as it is also known that lower limbs spasticity is an indicator of risk of falling (Soyuer 2007, Martin 2014). The most valuable data come from the analysis of quality of life scales; the treatment also had a relevant positive impact on patients’ quality of life and psychological status. The Short-Form 36 showed a significant improvement in the domains of Physical Role, Emotional Role, Social Function and Mental Health. The Hospital Anxiety scale showed a clear-cut improvement in the hanxiety domain. Little is known about the psychosocial impact of disease and Health-Related Quality
of Life (HRQoL) in patients with HSP; it is known that subjective perception of well-being is worse then in healthy subjects, and a more severe affection of physical aspects of quality of life compared to mental aspects is documented. It is also known that subjective perception of well-being is closely related to disease severity, especially to walking ability (Klimpe 2012, Braschinsky 2011) and therefore that QoL is significantly affected by ADL indipendence (Takemasa 2014). For these reasons rehabilitation programs should focus on improving patients’ indipendence in ADL and individual’s perception of well-being is an important fac-tor that should be considered with regards to chronically ill and disabled patients (Swanson 1993). Previous studies enrolling HSP patients assess that HRQoL is a valid parameter in HSP that should be considered in upcoming therapeutical trials (Klimpe 2012), and therefore it is important to highlight the impact of the innovative rehabilitation protocol proposed in this study on HSP patients’ subjective well-being. 5. Conclusion Our study indicates that a robotic gait training is long term effective in improving balance and walking ability with a positive impact on quality of life in patients affected by uncomplicated form of HSP. As currently there is no specific treatment to prevent or reverse HSP progression, our contribution would be significant for the development of exercise recommendations in this rare disease. Declaration of interest I declare that each author participated sufficiently in the work to take public responsibility for the content. I affirm that I had access to all data from the study, both what is reported and what is unreported, and also that I had complete freedom to direct its analysis and its reporting, without influence from sponsors. I also affirm that there was no editorial direction or censorship from the sponsors. No part of this work has been published. No conflict of interest exists. References Bjelland, I., Dahl, A. A., Haug, T. T., & Neckelmann, D. (2002). The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J Psychosom Res, 52, 69-77.
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