Effects of intensive arm training with the rehabilitation robot ARMin II in chronic stroke patients: four single-cases

Stroke remains the leading cause of permanent disability. Recent studies estimate that it affects more than 1 million people in the EU [1, 2] and more than 0.7 million in the U.S. each year [3]. The major symptom of stroke is severe sensory and motor hemiparesis of the contralesional side of the body [4]. The degree of recovery highly depends on the severity and the location of the lesion [5]. However, only 18% of stroke survivors regain full motor function after six months [6]. Restoration of arm and hand functions is essential [6] to cope with tasks of daily living and regain independence in life.

There is evidence that the rehabilitation plateau can be prolonged beyond six months post-stroke and that improvements in motor functions can be achieved even in a chronic stage with appropriate therapy [7, 8]. For this to occur, effective therapy must comprise key factors containing repetitive, functional, and task-specific exercises performed with high intensity and duration [9–12]. Enhancing patients' motivation, cooperation, and satisfaction can reinforce successful therapy [13]. Robot-assisted training can provide such key elements for inducing long-term brain plasticity and effective recovery [14–19].

Robotic devices can objectively and quantitatively monitor patients' progress - an additional benefit since clinical assessments are often subjective and suffer from reliability issues [20]. Patient-cooperative control algorithms [21, 22] can support patients' efforts only as much as needed, thus allowing for intensive robotic intervention.

Several clinical studies have been successfully conducted with endeffector based robots [14, 16, 17, 23]. In these robots, the human arm is connected to the robot at a single (distal) limb only. Consequently, endeffector based robots are easy to use but do not allow single joint torque control over large ranges of motion. In general, they provide less guidance and support than exoskeleton robots [24]. In this study we propose using an exoskeleton-type robot for the intervention. Such a type of robot provides superior guidance and permits individual joint torque control [24]. The device used here is called ARMin and has been developed over the last six years [21, 25].

A first pilot study with three chronic stroke patients showed significant improvements in motor functions with intensive training using the first prototype ARMin I. Since ARMin I provided therapy only to the shoulder and elbow, there were no improvements in distal arm functions [25]. Consequently, the goal was to develop a robot, which enables a larger variability of different (also more complex and functional) training modalities involving proximal and distal joint axes [26, 27].

For this study we used an enhanced prototype, ARMin II, with six independently actuated degrees of freedom (DOF) and one coupled DOF (Figure 1). The robot trains both proximal joints (horizontal and vertical shoulder rotation, arm inner - outer rotation, and elbow flexion - extension) and distal joints (pro - supination of lower arm and wrist flexion - extension). Together with an audiovisual display, ARMin II provides a wide variety of training modes with complex exercises and the possibility of performing motivating games.

The goal of this study was to investigate the effects of ARMin II training on motor function, strength and use in everyday life.

The results of the FMA are presented in Table 1. From baseline to discharge, patients 1, 2, and 3 increased their scores significantly (p < 0.05). They continued to improve in the FMA at the six-month follow-up (see Figure 3).

FMA: Total§ sh/e§ w/h§	Baseline	Post- therapy	Difference†	Follow up (6 mt)	Difference‡	Total change	R2	p
S1: Total	21	38.6	+17.6	50	+11.4	+29	0.943	0.001*
sh/e	20	24.0	+4.0	28	+4.0	+8
w/h	1	14.6	+13.6	22	+7.4	+21
S2: Total	24	27.1	+3.1	29	+1.9	+5	0.800	0.041*
sh/e	21	23.1	+2.1	24	+0.9	+3
w/h	3	4.0	+1.0	5	+1.0	+2
S3: Total	11	17.8	+6.8	19	+1.2	+8	0.908	0.003*
sh/e	10	15.8	+ 5.8	18	+2.2	+8
w/h	1	2.0	+1.0	1	-1.0	+0
S4: Total	10	12.1	+2.1	13	+0.9	+3	0.408	0.172
sh/e	10	12.1	+2.1	12	-0.1	+2
w/h	0	0	+0	1	+1.0	+1

Note: An increase in score indicates improvement. S1 - S4 means subject 1 to 4.

§Fugl-Meyer (FMA), total score, maximum = 66; score for shoulder/elbow (sh/e), max. = 36; score for wrist/hand (w/h), max. = 30

†Difference of score between baseline and post-test.

‡Difference of score between post-test and follow up.

*Indicate significant p-values < 0.05

Patient 1 gained +17.6 points in the FMA (from 21 to 38.6 points), while at the follow-up, six months later, he demonstrated even further impressive progress, without having received additional therapy in the mean time. Overall, patient 1 showed an absolute improvement of +29 points (from 21 to 50 points), particularly due to high recovery in distal arm functions (+21 points).

The FMA gains of patients 2 and 3 were +5 points (from 24 to 29 points) and +8 points (from 11 to 19 points). These findings were in line with other investigations about the effects of robot-assisted therapy in chronic stroke patients that demonstrated changes between 3.2 and 6.8 points [14, 23, 39–43]. However, one must note that such comparisons have to be done with care since studies often differ in methods and criteria (e.g. intervention time, number of training sessions per week, duration of training sessions, type of stroke, affected brain side, time post-stroke, and severity of lesion). Patient 4 showed an increase of +3 points (from 10 to 13 points) in the FMA; however, this increase was statistically not significant.

Typical arm functions that are relevant for activities of daily life can be expressed by the WMFT (Table 2). During the therapy, the WMFT scores of patients 1, 2 and 3 increased by +1.00, +0.5, and +0.86 points, respectively. Patients 2 and 3 slightly diminished at follow-up. Nevertheless, these three patients achieved significant progress (p < 0.05), in contrast to patient 4, who showed no significant improvement. However, at the follow-up examination, patient 4 was the only one who further improved in the WMFT (see Figure 4).

WMFT§	Baseline	Post- therapy	Difference†	Follow up (6 mt)	Difference‡	Total change	R2	p
S1:	1.86	2.86	+1.00	2.86	0	+1.00	0.911	0.003*
S2:	2.07	2.57	+0.50	2.50	-0.07	+0.43	0.891	0.005*
S3:	1.07	1.93	+0.86	1.79	-0.14	+0.72	0.831	0.011*
S4:	0.93	1.07	+0.14	1.29	+0.22	+0.36	0.577	0.080

Note: An increase in score indicates functional improvement. S1 - S4 means subject 1 to 4.

§Wolf Motor Function Test (WMFT), 5 = normal motor functions.

*Indicate significant p-values < 0.05

A questionnaire was used to obtain further information about patient status. The patients reported progress of the affected upper extremity in everyday life activities (e.g. the arm can be lifted higher and better, is more integrated, feels lighter and is less stiff, able to lift glass, fold laundry, use index finger, and control motions better). The grades of patients 1 to 4 regarding the use of their impaired arm during ADLs after the intervention (scale range 1 to 10, no better use = 1, much better use = 10) were 5, 7, 4 and 3, respectively. Furthermore, they described to be more motivated and willing to try to engage their arm in diverse daily activities.

Patients 1, 2 and 3 completed measurements and therapy sessions, except for patient 4, who missed one measurement date and two therapy sessions for reasons that are not related to the study.

In this study, intensive therapy using the robot ARMin II was administered to four chronic stroke patients during eight weeks of training. Patients 1 and 4 received 32 and 30 hours of therapy respectively, while patients 2 and 3 received 24 hours.

The results of these single-case series underline prior findings with robotic therapy, namely that intensive, repetitive, task-specific, and goal-directed training can significantly improve motor functions in chronic stroke patients - even years post-stroke [14, 23, 44]. All four patients demonstrated improvements in motor and functional activities, but to various degrees. Overall, they sustained their functional gains at the six-month follow-up or even continued to improve after the end of treatment, indicating potential long-term benefits of robot-assisted therapy.

Patient 4 had the lowest motor functions at study entrance and hardly any sensation in the clinical pinprick test. Such neurological deficits can make functional therapy very difficult as feedback functions are not, or hardly, available. This might explain why patient 4 could only profit little from the training with ARMin II. For stroke individuals with little sensory functions, as e.g. patient 4, a sensory intervention is suggested to be a more effective approach [45]. In general, it can be said that stroke patients with severe sensory loss benefited less from treatment than moderately impaired patients [10, 46].

The different responses of this pilot research could be explained by patients' heterogeneity, as patients differed in terms of age, time post-stroke, affected brain areas, sensation, muscle tone, etc. (Table 4) - all factors that influence motor relearning. The highest motor recoveries were experienced by patient 1, the youngest and least chronic patient. But note that patient 1 like patient 4 received more intensive intervention than the other two patients. It seems that treatment, with additional therapy hours, is primarily fruitful and beneficial for patients with a certain level of remaining sensory functions and motor abilities.

In a comparable study that has been conducted with the robot ARMin I, patients I and II received 24 hours of therapy, while patient III received 40 hours. The improvement of patients I, II and III were +3.1, +3.0, and +4.2 points (initial FMA scores were 14, 26 and 15).

The reason for the less distinctive improvements with the former version ARMin I and other previous robots might be due to the limited movement capabilities (only proximal [14, 47, 48] or distal [49] arm involvement) or the missing control of proximal joints (endeffector-based robots). In contrast, ARMin II allows for authentic motion sequences, including coordinated interactions between wrist, elbow and shoulder joints. This seems to be an important feature since most everyday activities are composed of inter-joint coordination. ARMin II is an exoskeleton-based robot and, in general, better suited to train ADL-tasks than an endeffector-based robot. This is because, in an exoskeleton robot, the human arm is very well supported and guided by the robot, movements with large ROM can be trained, and the interaction torques that the robot apply to each joint of the human arm can be controlled individually.

Complex movements also enable patients to break abnormal synergy patterns that are limiting arm motor functions [50–52]. As ARMin II provides support against gravity, abnormal synergy patterns in hemiparetic limbs can progressively be learned to be overcome, a matter that was observed in patients 1, 2 and 3. For this therapy issue, the labyrinth scenario seemed to be particularly suitable, as the parameters can be highly varied and adapted individually to the patient's needs. Similar to these findings, Sukal et al. [53] have shown in their research that a reduced range of motion in stroke patients was a result of pathologic synergies during arm lifting. By de-weighting and supporting the impaired arm in training sessions, the effect of gravity could be overcome.

Another approach by Ellis et al. [52] demonstrated that abnormal joint torque coupling could be modified by 'multi-DOF progressive resistance training' in severely impaired chronic stroke individuals. Patients gained strength and simultaneously improved in multi-DOF joint torque combinations. The same relationship could also be observed in the patients that participated in this pilot study. An increase in muscle strength was associated with a larger active range of motion as well as improved muscle coordination. Patients dissociated from synergistic co-activation in the FMA and WMFT.

A distinct finding of the ARMin II study was that post-treatment further progress was achieved in the FMA. These continuing improvements might be due to therapy of distal arm functions since neither the ARMin I study showed such additional effects at follow-up nor any other proximal robotic study in literature that the authors are aware of. Krebs et al. [41] found that training of the more distal limb segments led to twice as much carryover effect to the proximal segments than vice-versa. Moreover, they observed that improvement in more distal segments continued significantly even without further training for that particular limb segment. This finding supports our assumption that the patients were better able to use their arm in daily activities after robotic treatment, allowing them to further improve at the six-month follow up.

With eight weeks of robot training, patient 1 enhanced his performance to such an extent (from initially 21 points to 50 points in the follow-up in the FMA) that he reached a higher functional state - opening up new therapy approaches like constrained induced movement therapy CIMT.

In the present study the two game scenarios (labyrinth and ball game), were particularly suitable to create an enjoyable, efficient and motivating intervention. Patients' interests could be incorporated into therapy by choosing different game settings and levels with miscellaneous arm positions and various joint axes. Nevertheless, complementary therapy modes focusing on specific ADL-tasks and/or virtual reality scenarios might additionally help to facilitate a transfer to ADLs [26, 27]. An additional hand module for opening and closing hand function and/or single finger functions would enable more specific and individualized therapy of hand and fingers, allowing for the implementation of more authentic ADL-tasks.

So far, treatment with robotic devices [17, 19, 54] shows no consistent improvement in functional abilities of daily activities. Although high functional improvements and a transfer to ADLs were achieved in this investigation, these findings are limited to single cases. The pilot study included only four, rather heterogeneous chronic stroke patients. Despite the fact that functional stability could be verified in all patients at baseline, no separate control group was used. All patients continued with their conventional outpatient therapies (maximum 1 hour of physical and occupational therapy per week, focusing on the gait and posture only). However, the patients were encouraged to continue their standard therapies on a constant level, so that possible improvements due to this small amount of conventional therapy can be excluded from the study. Overall, these encouraging results definitely justify starting a large randomized clinical trial.

This paper presents preliminary results of a pilot study with four heterogeneous, chronic stroke patients using the robotic device ARMin II. The findings support the assumption that robot therapy can significantly influence therapy outcomes. A robot that includes proximal and distal joints, such as ARMin II, allows for a wide field of specific training modalities with natural and complex motions.

In this study it was noted that a subgroup of patients could achieve a transfer to ADLs after performing the training phase. This finding is of great importance since treatment with robotic devices to date did not result in consistent improvement in activities of daily living. A transfer to everyday life should be indeed a central intention of rehabilitation as it brings independence and improve quality of life.