Accepted Manuscript Invited Commentary on Comparison of Robotics, FES, and Motor Learning Methods for Treatment of Persistent Upper Extremity Dysfunction after Stroke: a Randomized Controlled Trial Gert Kwakkel, Erwin E.H. van Wegen, C. Meskers PII:
S0003-9993(15)00111-2
DOI:
10.1016/j.apmr.2015.02.004
Reference:
YAPMR 56108
To appear in:
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
Received Date: 6 December 2014 Revised Date:
8 January 2015
Accepted Date: 4 February 2015
Please cite this article as: Kwakkel G, van Wegen EEH, Meskers C, Invited Commentary on Comparison of Robotics, FES, and Motor Learning Methods for Treatment of Persistent Upper Extremity Dysfunction after Stroke: a Randomized Controlled Trial, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2015), doi: 10.1016/j.apmr.2015.02.004. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Invited Commentary on Comparison of Robotics, FES, and Motor Learning Methods for Treatment of Persistent Upper Extremity Dysfunction after Stroke: a Randomized Controlled Trial Gert Kwakkel (1,2) Erwin E. H. van Wegen (1) C. Meskers (1)
RI PT
1. Dept. of Rehabilitation Medicine, VU University Medical Centre, MOVE Research Institute Amsterdam, PO Box 7057, 1007 MB, Amsterdam, The Netherlands. § Corresponding author 2. Dept. of Neurorehabilitation, Reade Centre of Rehabilitation and Rheumatology, P.O. Box 58271, 1040 HG, Amsterdam, The Netherlands.
SC
Corresponding author: Prof. dr. G. Kwakkel
TE D
phone: +31-20-4440460 Secr.: Helma Kruijk Phone: +31-20-4441940 Fax: +31-20-4440787
M AN U
Chair of Neurorehabilitation Dept. Rehabilitation Medicine VU University Medical Center de Boelelaan 1117 1081 HV Amsterdam PO Box 7057 1007 MB Amsterdam The Netherlands
AC C
EP
E-mail: [email protected]
ACCEPTED MANUSCRIPT Invited Commentary on Comparison of Robotics, FES, and Motor Learning Methods for Treatment of Persistent Upper Extremity Dysfunction after Stroke: a Randomized Controlled Trial Abstract [194 Words] In this issue of Archives of Physical Medicine and Rehabilitation, Jessica McCabe and colleagues report findings
RI PT
from their methodologically sound dose-matched clinical trial in 39 patients beyond 6 months post stroke. In this phase II trial, the effects of 60 treatment sessions, each involving 3.5 hours of intensive practice plus either 1.5 hours of functional electrical stimulation (FES) or a shoulder-arm robotic therapy, were compared with 5 hours of intensive daily practice alone. Although no significant between-group differences were found on the primary outcome measure of Arm Motor Ability Test (AMAT) and the secondary outcome measure of Fugl
SC
Meyer Arm (FMA) motor score, 10 to 15% within-group therapeutic gains were observed regarding AMAT and FMA. These gains are clinically meaningful for patients with stroke. However, the underlying mechanisms that drive these improvements remain poorly understood. The approximately 1000 dollar cost reduction per patient
M AN U
calculated for the use of motor learning (ML) methods alone or combined with FES, compared to the combination of ML and shoulder arm-robotics, further emphasizes the need for cost considerations when making clinical decisions about selecting the most appropriate therapy for the upper paretic limb in clients suffering from chronic stroke.
Keywords:
List of abbreviations: FMA: Fugl-Meyer Arm test
EP
AMAT: Arm Motor Ability Test
TE D
Stroke, Rehabilitation, Upper Extremity, Robotics, Electric Stimulation
FES: Functional Electrical Stimulation
AC C
ML: Motor Learning
(m)CIMT: (modified) Constraint Induced Movement Therapy ARAT: Action Research Arm Test
1
ACCEPTED MANUSCRIPT [1812 Words] We would like to congratulate Dr. Jessica McCabe and her colleagues on their methodologically sound dosematched proof-of-concept trial, in which they showed that motor recovery in chronic stroke is mainly driven by intensity of practice, rather than by differences in the type of intervention applied (i.e., ML methods alone or combined with robotics or functional electrical stimulation [FES]) (1). All three groups received an exceptional high dose of 5 times a week for 5 hours a day, totaling 60 sessions of therapy applied beyond 6 months post
RI PT
stroke. Although no significant differences were found between the three arms of this neutral trial, significant gains were seen within the three groups with respect to the speed of performing the 13 complex tasks of the Arm Motor Ability Test (AMAT), such as opening a jar or putting on a T-shirt. In line with results from the primary outcome measure AMAT, no significant between-group differences were found on the secondary motor outcome, the Fugl-Meyer Arm (FMA) test. However, significant within-group improvements were found,
SC
ranging from 7 to 10 points, irrespective of the type of treatment protocol, i.e., ML methods alone, FES with ML or Robotics with ML. The results of the trial support the notion that even severely affected chronic stroke
M AN U
patients may show clinically meaningful gains ranging from 10 to 15% in their motor performance with daily intensive practice. The observed gains in arm-hand capacity are in line with those of other interventions in which intensity of practice is augmented for a few weeks, such as constraint induced movement therapy (CIMT) or modified versions of CIMT (2).
The lack of significant between-group differences in the present trial is likely the result of insufficient treatment contrast between the three arms regarding the type of therapy applied, as well as the low numbers recruited in
TE D
this proof-of-concept trial (39 patients randomized over three arms). Probably, the low numbers have resulted in type II error. In fact, only 1.5 of the 5 hours a day over 60 treatment sessions were specifically spent on FES or shoulder-arm robotics, implying only 90 (about 30%) of the total of 300 hours of therapy, whereas the control group received 300 hours of ML methods. The neutral findings of the trial by McCabe and colleagues
EP
are in line with a recent systematic review involving 467 trials in the field of motor rehabilitation after stroke. This review suggests that additional effects of technology-driven exercise therapy such as FES or Robotics are limited, and have so far only been shown in non-dose-matched trials in which the experimental group received
AC C
more repetitions and/or spent more time practicing clinically meaningful tasks (3). In fact, none of the dosematched trials on upper (and lower) limb rehabilitation have so far found an added value of technologysupported devices including robotics (3). Understanding benefits within groups The present study further shows that chronic patients with a severe pre-treatment motor deficit may also benefit from very intensive deliberate practice, in terms of upper limb capacity and motor performance. Interestingly, the within-group gains in all intervention arms of the trial were larger for the FMA wrist and hand function (15–23%) than for the shoulder elbow function (11–12%). Unfortunately, the pre-post measurements used in the present study do not allow any conclusions as to how these improvements emerge over time, due to the lack of data at intermediate time points. The next challenge for scientists will be to unravel the time
2
ACCEPTED MANUSCRIPT course of ML and to determine what exactly patients learn during motor rehabilitation. Both topics are essential to understand the mechanisms that drive the observed meaningful improvements in functional outcome from intensive practice in chronic stroke. As suggested previously (4,5), this urgently requires intensive, repeated measurement designs in which changes in structure and body functions including changes in coordination dynamics are monitored systematically at fixed time points post stroke (4,5).
RI PT
An important question that needs to be addressed will be: Is the time course of therapy-induced improvements in chronic stroke linear over (i.e., parallel to) the 60 treatment sessions or do the therapy-induced gains occur mainly in the first days after starting the ML therapy? Although the literature is rather scarce and inconclusive on this topic, Reinkensmeyer and colleagues showed in their sample of 27 chronic stroke patients that ML follows an exponential time-course of recovery irrespective of robot support (6). In a subsequently derived
SC
neuro-computational model, they showed that the time course of this ML curve depended on patients’ ability to activate the spared portions of the damaged corticospinal tract system (6). Similarly, neuro-computational simulation models based on findings from the Extremity Constraint-Induced Therapy Evaluation (EXCITE) trial
M AN U
suggest that ML induced by CIMT requires a minimum motor performance threshold to accomplish meaningful improvements and to reverse use-dependent phenomena such as learned non-use (7). Remarkably, the present trial suggests that even patients with severe upper limb paresis according to the FMA may benefit from a very high-dose of deliberate practice in the chronic phase post stroke. Above finding puts further emphasis on the need to identify the patient characteristics that may distinguish responders from non-responders to intensive practice in chronic stroke. In fact, the study by McCabe et al provides further evidence that therapy
TE D
dosage should always be carefully considered when research is planned and performed (8). To explain the clinically meaningful within-group gains in the trial of McCabe and colleagues, one may hypothesize that chronic patients with incomplete upper limb recovery are likely to behave at lower motor performance levels than they are potentially able to in terms of capacities. This hypothesis suggests a mismatch
EP
between what patients actually show in Activities of Daily Living, and what their maximal ability is. This phenomenon has already been observed more than a century ago in hemiplegics and classified as “functional
AC C
motor amnesia” and more recently as “learned non-use” (See for an historical view: Andre et al (9)). Obviously, the underperformance in motor control in daily life as a reflection of “learned non-use” is more often seen in patients with an incomplete upper limb paresis, and was in some trials most frequently observed in patients with an incomplete arm-hand capacity (i.e., scores of 10–54 points on the Action Research Arm Test; ARAT). In addition, this mismatch between what stroke patients prefer to do with their upper paretic limb in daily life and what they are actually able to do is more pronounced in those with somatosensory impairments and/or hemi-neglect (10). Unfortunately, the small sample of 39 chronic stroke victims in the present study by McCabe and colleagues does not allow identification of the characteristics of responders and non-responders to intensive practice. Future studies should establish the number of patients that are susceptible for deterioration in upper paretic limb function due to learned non-use as well as the determinants related with learned nonuse.
3
ACCEPTED MANUSCRIPT Mechanisms that drive deliberate practice in chronic stroke. A major challenge for scientists will be to uncover the underlying mechanisms of therapy-induced improvements. Based on the current data it remains unclear whether these changes signify true motor recovery towards a pre-morbid, healthy state (i.e. restitution) or whether they reflect the invocation of adaptive control strategies by which patients learn to compensate for existing neurological deficits (i.e. substitution) (5). For example, in a controlled proof of concept study, Kitago and colleagues found no
RI PT
significant changes in coordinative measures of the paretic arm and wrist after modified CIMT in chronic stroke, despite clinically meaningful functional improvements in ARAT scores (11). This finding suggests that improvements introduced by deliberate practice after chronic stroke are mainly based on learning to optimize the use of intact end-effectors (ie, compensation strategies). This finding is likely not to be different from
SC
therapy-induced gains observed early post stroke, despite the growing evidence of increased levels of (homeostatic) neuroplasticity within in the first weeks post stroke (12). Similar to the chronic phase, there is growing evidence that also in the acute phase patients learn to optimize their motor performance by using,
M AN U
whether or not, spontaneously returned intact end-effectors in a more efficient way (13,14). This latter assumption suggests that irrespective of the rather proportional fixed amount of spontaneous neurological recovery (15), the therapy-induced improvements due to deliberate practice in the first weeks are likely not to be different from the adaptive strategies seen in the chronic stage after stroke (11). It should be noted however, that studies that started very early post stroke are scarce and in most cases are underpowered (2,3)
TE D
Costs considerations
Important from a health-care perspective is that the present trial shows that the mean costs of intensive daily practice applied in a 1 to 3 staff:patient ratio was about $1000 less for the ML methods and FES groups than for the group treated with the commercially available InMotion2-Shoulder-Elbow-Robot. This important finding
EP
further emphasizes the need for cost considerations when making clinical decisions about selecting evidencebased therapies with a clinically meaningful impact in patients with chronic stroke. For example, a recently published single-blinded trial involving 77 chronic stroke patients showed that 24 sessions of 45 minute training
AC C
with the most advanced commercially available exoskeleton arm robot (ARMin), was not more effective in terms of FM-arm scores than equally dosed conventional care (16). Although the authors found statistically significant effects favoring the ARMin robot on their primary measurement of outcome FMA, the betweengroup difference of 0.78 points was clinically meaningless when compared to conventional care (17). Unfortunately, none of the dose-matched trials that investigated upper limb robotics, have shown a surplus value when compared to dose-matched conventional practice (3). This finding seems independent from complexity of the robot tested and accompanying costs. This observation suggests that bio-engineers that aim to develop commercial available shoulder-arm robotics should take costs into consideration.
References:
4
ACCEPTED MANUSCRIPT 1.
2. 3.
RI PT
4. 5.
McCabe J, Monkiewicz M, Holcomb J, Pundik S, Daly J. Comparison of Robotics, FES, and Motor Learning Methods for Treatment of Persistent Upper Extremity Dysfunction after Stroke: a Randomized Controlled Trial Manuscript Number: ARCHIVES-PMR-D-14-00993R1 Kwakkel Veerbeek JM, van Wegen EEH, Wolf SL. Constraint-induced movement therapy after stroke. Lancet Neurology 2015 S1474-4422(14)70160-7. Veerbeek JM, van Wegen E, van Peppen R, van der Wees PJ, Hendriks E, Rietberg M, Kwakkel G. What is the evidence for physical therapy poststroke? A systematic review and meta-analysis. PLoS One. 2014 Feb 4;9(2):e87987. Langhorne P, Bernhardt J, Kwakkel G. Stroke rehabilitation. Lancet. 2011 May 14;377(9778):1693-702. Buma F, Kwakkel G, Ramsey N. Understanding upper limb recovery after stroke. Restor Neurol Neurosci. 2013;31(6):707-22. doi: 10.3233/RNN-130332. Review.PubMed PMID: 23963341. Reinkensmeyer DJ, Maier MA, Guigon E, Chan V, Akoner O, Wolbrecht ET, Cramer SC, Bobrow JE. Do robotic and non-robotic arm movement training drive motor recovery after stroke by a common neural mechanism? Experimental evidence and a computational model. Conf Proc IEEE Eng Med Biol Soc. 2009;2009:2439-41. Schweighofer N, Han CE, Wolf SL, Arbib MA, Winstein CJ. A functional threshold for long-term use of hand and arm function can be determined: predictions from a computational model and supporting data from the Extremity Constraint-Induced Therapy Evaluation (EXCITE) Trial. Phys Ther. 2009 Dec;89(12):1327-36. Pollock A, Farmer SE, Brady MC, Langhorne P, Mead GE, Mehrholz J, van Wijck F. Interventions for improving upper limb function after stroke. Cochrane Database of Systematic Reviews 2014, Issue 11. Art. No.: CD010820. André JM, Didier JP, Paysant J. "Functional motor amnesia" in stroke (1904) and "learned non-use phenomenon" (1966). J Rehabil Med. 2004 May;36(3):138-40. Van der Lee, J. H., Wagenaar, R. C., Lankhorst, G. J., Vogelaar, T. W., Deville, W. L., & Bouter, L. M. (1999). Forced use of the upper extremity in chronic stroke patients: Results from a single-blind randomized clinical trial. Stroke, 30(11), 2369–2375. Kitago T, Liang J, Huang VS, Hayes S, Simon P, Tenteromano L, Lazar RM, Marshall RS, Mazzoni P, Lennihan L, Krakauer JW. Improvement after constraint-induced movement therapy: recovery of normal motor control or task-specific compensation? Neurorehabil Neural Repair. 2013 Feb;27(2):99109. Murphy TH, Corbett D. Plasticity during stroke recovery: from synapse to behaviour. Nat Rev Neurosci. 2009;10:861–72. van Kordelaar J, van Wegen EE, Nijland RH, Daffertshofer A, Kwakkel G.Understanding adaptive motor control of the paretic upper limb early poststroke: the EXPLICIT-stroke program. Neurorehabil Neural Repair. 2013 Nov-Dec;27(9):854-63. van Kordelaar J, van Wegen E, Kwakkel G. Impact of time on quality of motor control of the paretic upper limb after stroke. Arch Phys Med Rehabil. 2014 Feb;95(2):338-44. Winters C, van Wegen EE, Daffertshofer A, Kwakkel G. Generalizability of the Proportional Recovery Model for the Upper Extremity After an Ischemic Stroke. Neurorehabil Neural Repair. 2014 Dec 11. pii: 1545968314562115. [Epub ahead of print] PubMed PMID: 25505223. Klamroth-Marganska V, Blanco J, Campen K, Curt A, Dietz V, Ettlin T, Felder M, Fellinghauer B, Guidali M, Kollmar A, Luft A, Nef T, Schuster-Amft C, Stahel W, Riener R. Three-dimensional, task-specific robot therapy of the arm after stroke: a multicentre, parallel-group randomised trial. Lancet Neurol. 2014 Feb;13(2):159-66. Kwakkel G, Meskers CG. Effects of robotic therapy of the arm after stroke. Lancet Neurol. 2014 Feb;13(2):132-3.
6.
10.
11.
12. 13.
14.
AC C
15.
TE D
9.
EP
8.
M AN U
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7.
16.
17.
5
S0003-9993(15)00111-2
DOI:
10.1016/j.apmr.2015.02.004
Reference:
YAPMR 56108
To appear in:
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
Received Date: 6 December 2014 Revised Date:
8 January 2015
Accepted Date: 4 February 2015
Please cite this article as: Kwakkel G, van Wegen EEH, Meskers C, Invited Commentary on Comparison of Robotics, FES, and Motor Learning Methods for Treatment of Persistent Upper Extremity Dysfunction after Stroke: a Randomized Controlled Trial, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2015), doi: 10.1016/j.apmr.2015.02.004. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Invited Commentary on Comparison of Robotics, FES, and Motor Learning Methods for Treatment of Persistent Upper Extremity Dysfunction after Stroke: a Randomized Controlled Trial Gert Kwakkel (1,2) Erwin E. H. van Wegen (1) C. Meskers (1)
RI PT
1. Dept. of Rehabilitation Medicine, VU University Medical Centre, MOVE Research Institute Amsterdam, PO Box 7057, 1007 MB, Amsterdam, The Netherlands. § Corresponding author 2. Dept. of Neurorehabilitation, Reade Centre of Rehabilitation and Rheumatology, P.O. Box 58271, 1040 HG, Amsterdam, The Netherlands.
SC
Corresponding author: Prof. dr. G. Kwakkel
TE D
phone: +31-20-4440460 Secr.: Helma Kruijk Phone: +31-20-4441940 Fax: +31-20-4440787
M AN U
Chair of Neurorehabilitation Dept. Rehabilitation Medicine VU University Medical Center de Boelelaan 1117 1081 HV Amsterdam PO Box 7057 1007 MB Amsterdam The Netherlands
AC C
EP
E-mail: [email protected]
ACCEPTED MANUSCRIPT Invited Commentary on Comparison of Robotics, FES, and Motor Learning Methods for Treatment of Persistent Upper Extremity Dysfunction after Stroke: a Randomized Controlled Trial Abstract [194 Words] In this issue of Archives of Physical Medicine and Rehabilitation, Jessica McCabe and colleagues report findings
RI PT
from their methodologically sound dose-matched clinical trial in 39 patients beyond 6 months post stroke. In this phase II trial, the effects of 60 treatment sessions, each involving 3.5 hours of intensive practice plus either 1.5 hours of functional electrical stimulation (FES) or a shoulder-arm robotic therapy, were compared with 5 hours of intensive daily practice alone. Although no significant between-group differences were found on the primary outcome measure of Arm Motor Ability Test (AMAT) and the secondary outcome measure of Fugl
SC
Meyer Arm (FMA) motor score, 10 to 15% within-group therapeutic gains were observed regarding AMAT and FMA. These gains are clinically meaningful for patients with stroke. However, the underlying mechanisms that drive these improvements remain poorly understood. The approximately 1000 dollar cost reduction per patient
M AN U
calculated for the use of motor learning (ML) methods alone or combined with FES, compared to the combination of ML and shoulder arm-robotics, further emphasizes the need for cost considerations when making clinical decisions about selecting the most appropriate therapy for the upper paretic limb in clients suffering from chronic stroke.
Keywords:
List of abbreviations: FMA: Fugl-Meyer Arm test
EP
AMAT: Arm Motor Ability Test
TE D
Stroke, Rehabilitation, Upper Extremity, Robotics, Electric Stimulation
FES: Functional Electrical Stimulation
AC C
ML: Motor Learning
(m)CIMT: (modified) Constraint Induced Movement Therapy ARAT: Action Research Arm Test
1
ACCEPTED MANUSCRIPT [1812 Words] We would like to congratulate Dr. Jessica McCabe and her colleagues on their methodologically sound dosematched proof-of-concept trial, in which they showed that motor recovery in chronic stroke is mainly driven by intensity of practice, rather than by differences in the type of intervention applied (i.e., ML methods alone or combined with robotics or functional electrical stimulation [FES]) (1). All three groups received an exceptional high dose of 5 times a week for 5 hours a day, totaling 60 sessions of therapy applied beyond 6 months post
RI PT
stroke. Although no significant differences were found between the three arms of this neutral trial, significant gains were seen within the three groups with respect to the speed of performing the 13 complex tasks of the Arm Motor Ability Test (AMAT), such as opening a jar or putting on a T-shirt. In line with results from the primary outcome measure AMAT, no significant between-group differences were found on the secondary motor outcome, the Fugl-Meyer Arm (FMA) test. However, significant within-group improvements were found,
SC
ranging from 7 to 10 points, irrespective of the type of treatment protocol, i.e., ML methods alone, FES with ML or Robotics with ML. The results of the trial support the notion that even severely affected chronic stroke
M AN U
patients may show clinically meaningful gains ranging from 10 to 15% in their motor performance with daily intensive practice. The observed gains in arm-hand capacity are in line with those of other interventions in which intensity of practice is augmented for a few weeks, such as constraint induced movement therapy (CIMT) or modified versions of CIMT (2).
The lack of significant between-group differences in the present trial is likely the result of insufficient treatment contrast between the three arms regarding the type of therapy applied, as well as the low numbers recruited in
TE D
this proof-of-concept trial (39 patients randomized over three arms). Probably, the low numbers have resulted in type II error. In fact, only 1.5 of the 5 hours a day over 60 treatment sessions were specifically spent on FES or shoulder-arm robotics, implying only 90 (about 30%) of the total of 300 hours of therapy, whereas the control group received 300 hours of ML methods. The neutral findings of the trial by McCabe and colleagues
EP
are in line with a recent systematic review involving 467 trials in the field of motor rehabilitation after stroke. This review suggests that additional effects of technology-driven exercise therapy such as FES or Robotics are limited, and have so far only been shown in non-dose-matched trials in which the experimental group received
AC C
more repetitions and/or spent more time practicing clinically meaningful tasks (3). In fact, none of the dosematched trials on upper (and lower) limb rehabilitation have so far found an added value of technologysupported devices including robotics (3). Understanding benefits within groups The present study further shows that chronic patients with a severe pre-treatment motor deficit may also benefit from very intensive deliberate practice, in terms of upper limb capacity and motor performance. Interestingly, the within-group gains in all intervention arms of the trial were larger for the FMA wrist and hand function (15–23%) than for the shoulder elbow function (11–12%). Unfortunately, the pre-post measurements used in the present study do not allow any conclusions as to how these improvements emerge over time, due to the lack of data at intermediate time points. The next challenge for scientists will be to unravel the time
2
ACCEPTED MANUSCRIPT course of ML and to determine what exactly patients learn during motor rehabilitation. Both topics are essential to understand the mechanisms that drive the observed meaningful improvements in functional outcome from intensive practice in chronic stroke. As suggested previously (4,5), this urgently requires intensive, repeated measurement designs in which changes in structure and body functions including changes in coordination dynamics are monitored systematically at fixed time points post stroke (4,5).
RI PT
An important question that needs to be addressed will be: Is the time course of therapy-induced improvements in chronic stroke linear over (i.e., parallel to) the 60 treatment sessions or do the therapy-induced gains occur mainly in the first days after starting the ML therapy? Although the literature is rather scarce and inconclusive on this topic, Reinkensmeyer and colleagues showed in their sample of 27 chronic stroke patients that ML follows an exponential time-course of recovery irrespective of robot support (6). In a subsequently derived
SC
neuro-computational model, they showed that the time course of this ML curve depended on patients’ ability to activate the spared portions of the damaged corticospinal tract system (6). Similarly, neuro-computational simulation models based on findings from the Extremity Constraint-Induced Therapy Evaluation (EXCITE) trial
M AN U
suggest that ML induced by CIMT requires a minimum motor performance threshold to accomplish meaningful improvements and to reverse use-dependent phenomena such as learned non-use (7). Remarkably, the present trial suggests that even patients with severe upper limb paresis according to the FMA may benefit from a very high-dose of deliberate practice in the chronic phase post stroke. Above finding puts further emphasis on the need to identify the patient characteristics that may distinguish responders from non-responders to intensive practice in chronic stroke. In fact, the study by McCabe et al provides further evidence that therapy
TE D
dosage should always be carefully considered when research is planned and performed (8). To explain the clinically meaningful within-group gains in the trial of McCabe and colleagues, one may hypothesize that chronic patients with incomplete upper limb recovery are likely to behave at lower motor performance levels than they are potentially able to in terms of capacities. This hypothesis suggests a mismatch
EP
between what patients actually show in Activities of Daily Living, and what their maximal ability is. This phenomenon has already been observed more than a century ago in hemiplegics and classified as “functional
AC C
motor amnesia” and more recently as “learned non-use” (See for an historical view: Andre et al (9)). Obviously, the underperformance in motor control in daily life as a reflection of “learned non-use” is more often seen in patients with an incomplete upper limb paresis, and was in some trials most frequently observed in patients with an incomplete arm-hand capacity (i.e., scores of 10–54 points on the Action Research Arm Test; ARAT). In addition, this mismatch between what stroke patients prefer to do with their upper paretic limb in daily life and what they are actually able to do is more pronounced in those with somatosensory impairments and/or hemi-neglect (10). Unfortunately, the small sample of 39 chronic stroke victims in the present study by McCabe and colleagues does not allow identification of the characteristics of responders and non-responders to intensive practice. Future studies should establish the number of patients that are susceptible for deterioration in upper paretic limb function due to learned non-use as well as the determinants related with learned nonuse.
3
ACCEPTED MANUSCRIPT Mechanisms that drive deliberate practice in chronic stroke. A major challenge for scientists will be to uncover the underlying mechanisms of therapy-induced improvements. Based on the current data it remains unclear whether these changes signify true motor recovery towards a pre-morbid, healthy state (i.e. restitution) or whether they reflect the invocation of adaptive control strategies by which patients learn to compensate for existing neurological deficits (i.e. substitution) (5). For example, in a controlled proof of concept study, Kitago and colleagues found no
RI PT
significant changes in coordinative measures of the paretic arm and wrist after modified CIMT in chronic stroke, despite clinically meaningful functional improvements in ARAT scores (11). This finding suggests that improvements introduced by deliberate practice after chronic stroke are mainly based on learning to optimize the use of intact end-effectors (ie, compensation strategies). This finding is likely not to be different from
SC
therapy-induced gains observed early post stroke, despite the growing evidence of increased levels of (homeostatic) neuroplasticity within in the first weeks post stroke (12). Similar to the chronic phase, there is growing evidence that also in the acute phase patients learn to optimize their motor performance by using,
M AN U
whether or not, spontaneously returned intact end-effectors in a more efficient way (13,14). This latter assumption suggests that irrespective of the rather proportional fixed amount of spontaneous neurological recovery (15), the therapy-induced improvements due to deliberate practice in the first weeks are likely not to be different from the adaptive strategies seen in the chronic stage after stroke (11). It should be noted however, that studies that started very early post stroke are scarce and in most cases are underpowered (2,3)
TE D
Costs considerations
Important from a health-care perspective is that the present trial shows that the mean costs of intensive daily practice applied in a 1 to 3 staff:patient ratio was about $1000 less for the ML methods and FES groups than for the group treated with the commercially available InMotion2-Shoulder-Elbow-Robot. This important finding
EP
further emphasizes the need for cost considerations when making clinical decisions about selecting evidencebased therapies with a clinically meaningful impact in patients with chronic stroke. For example, a recently published single-blinded trial involving 77 chronic stroke patients showed that 24 sessions of 45 minute training
AC C
with the most advanced commercially available exoskeleton arm robot (ARMin), was not more effective in terms of FM-arm scores than equally dosed conventional care (16). Although the authors found statistically significant effects favoring the ARMin robot on their primary measurement of outcome FMA, the betweengroup difference of 0.78 points was clinically meaningless when compared to conventional care (17). Unfortunately, none of the dose-matched trials that investigated upper limb robotics, have shown a surplus value when compared to dose-matched conventional practice (3). This finding seems independent from complexity of the robot tested and accompanying costs. This observation suggests that bio-engineers that aim to develop commercial available shoulder-arm robotics should take costs into consideration.
References:
4
ACCEPTED MANUSCRIPT 1.
2. 3.
RI PT
4. 5.
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