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Virtual reality in multiple sclerosis rehabilitation: A review on cognitive and motor outcomes
Journal of Clinical Neuroscience xxx (xxxx) xxx
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Review article
Virtual reality in multiple sclerosis rehabilitation: A review on cognitive and motor outcomes Maria Grazia Maggio a, Margherita Russo b, Marilena Foti Cuzzola a, Massimo Destro a, Gianluca La Rosa a, Francesco Molonia a, Placido Bramanti a, Giuseppe Lombardo a, Rosaria De Luca a, Rocco Salvatore Calabrò a,⇑ a b
IRCCS Centro Neurolesi ‘‘Bonino Pulejo”, Messina, Italy U.O.C. Neurologia GOM Melacrino-Morelli-Bianchi, Reggio Calabria, Italy
a r t i c l e
i n f o
Article history: Received 26 January 2019 Accepted 11 March 2019 Available online xxxx Keywords: Cognitive rehabilitation Multiple sclerosis Virtual reality training
a b s t r a c t Multiple sclerosis (MS) is a demyelinating neurodegenerative disease with lesions involving the central nervous system. Clinical symptoms consist of disturbances in motor activity (e.g., weakness, spasticity, and tremor), sensory functioning (e.g., pain), visual functions (e.g., diplopia and optic neuritis), besides different cognitive (attention deficit and executive dysfunction) and behavioral abnormalities. This review aims to evaluate the role of VR tools in cognitive and motor rehabilitation of MS patients. Studies performed between 2010 and 2017 and fulfilling the selected criteria were searched on PubMed, Scopus, Cochrane and Web of Sciences databases, by combining the terms ‘‘VR rehabilitation” and ‘‘MS”. Our findings showed that, following the use of VR training, MS patients presented a significant improvement in motor (especially gait and balance) and cognitive function (with regard to executive and visual-spatial abilities, attention and memory skills). This review supports the idea that rehabilitation through new VR tools could positively affect MS patients’ outcomes, by boosting motivation and participation with a better response to treatment. Ó 2019 Elsevier Ltd. All rights reserved.
1. Introduction Multiple sclerosis (MS) is a demyelinating neurodegenerative disease with lesions involving the central nervous system. Indeed, the disease is largely caused by autoimmune processes that produce loss of myelin in the white matter of the cerebral hemispheres, brainstem, cerebellum, spinal cord, and optic nerves [1,2]. MS prevalence varies from 15/100.000 to 250/100.000, and it is estimated that two million people worldwide suffer from MS, and the disease is one of the most common causes of neurological disability in young adults [3]. The prevalence of MS in Italy estimates around 193 cases per 100.000 inhabitants, with the exception of Sardinia (360 cases for 100.000 inhabitants) [4]. The disease typical onset is around at 30 years, and is mostly diagnosed in women between 20 and 40 years. Clinically, most MS patients experience recurrent episodes (relapses) of neurological impairment, but in most cases (60% –80%), the course of the pathology becomes chronic and progressive with time, leading to cumulative ⇑ Corresponding author at: IRCCS Centro Neurolesi ‘‘Bonino-Pulejo”, S.S. 113, Contrada Casazza, 98124 Messina, Italy. E-mail address: [email protected] (R.S. Calabrò).
motor disability and cognitive deficits. MS presents a broad range of symptoms because of the widespread nature of the disease lesions within the CNS. Clinical symptoms consist of disturbances in motor activity (e.g., weakness, spasticity, and tremor), sensory functioning (e.g., pain), visual functions (e.g., diplopia and optic neuritis), besides different cognitive (attention deficit and executive dysfunction) and behavioral abnormalities [2,5,6]. MS therapy aims to slow down the course and treat the symptoms. The drugs used (immunosuppressants, immunomodulators, corticosteroids) are designed to shorten the relapse, reduce its severity and delay the progression of the disease. Instead, rehabilitation is oriented towards the re-education of motor and cognitive dysfunctions, and this is essential to favor the activities of daily life, permitting the strengthening of residual capacities and the learning of new strategies. The motor rehabilitation mainly used are conventional physiotherapy and kinesitherapy that reduce the difficulties related to spasticity, pain and fatigue. Furthermore, the conventional cognitive rehabilitation (CR) i.e. paper-pencil exercises, seems to be useful to increase cognitive abilities. In recent years, the use of VR has been introduced in the field of neurological rehabilitation, especially in patients with stroke, or Parkinson’s disease, and in children with cerebral palsy [7–11]. A recent study
https://doi.org/10.1016/j.jocn.2019.03.017 0967-5868/Ó 2019 Elsevier Ltd. All rights reserved.
Please cite this article as: M. G. Maggio, M. Russo, M. F. Cuzzola et al., Virtual reality in multiple sclerosis rehabilitation: A review on cognitive and motor outcomes, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.03.017
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performed by Doniger and colleagues showed the efficacy of a VRbased cognitive-motor training program on a cohort of patients affected by Alzheimer’s Disease [12]. In addition, a recent systematic review concerning computerized and VR cognitive training for individuals with mild cognitive impairment and dementia found consistent improvements in the cognitive domains of attention, executive function, and memory (visual and verbal), as well as significant reductions in depressive symptoms and anxiety, after these innovative interventions [13]. The use BTs-Nirvana on the recovery of cognitive and motor functions in stroke patients, using the Interactive-Semi-Immersive scenarios, has been proven to be effective, especially regarding attention and visual-spatial deficits, besides trunk control [14–16]. The role of VR as rehabilitative tool in MS patients is still under debate. Many studies have confirmed the important role of VR in both motor and cognitive rehabilitation (CR) [17–20]. The virtual interactive experience increases the self-efficacy of the subject affected by MS, and it can play an active role in similar environments with an increased knowledge and self-consciousness, and a higher self-consciousness in the environment and the development of the motor and cognitive components, as well as increasing the Motivation and the Interest [17–20]. Moreover, growing evidence in literature is supporting the idea of the pivotal role of VR coupled to robotic rehabilitation in improving motor and cognitive performances in MS patients [17]. In detail, Calabrò and coworkers showed not only a greater improvement in balance in individuals undergoing VR but also an improvement in the psychological outcomes, as shown by coping strategies improvement (Table 1).
This review aims to evaluate the role of VR in the rehabilitation of MS patients, with regard to motor and cognitive outcome. 2. Search strategy The studies were identified by searching on Scopus, PubMed, Web of Science, and Cochrane database all the studies fulfilling our selected criteria and published between 2007 and 2018 (see Fig. 1). The search combined the following terms: ‘‘virtual reality”[MeSH Terms] OR ‘‘virtual”[All Fields] AND ‘‘reality”[All Fields] OR ‘‘virtual reality”[All Fields] AND ‘‘multiple sclerosis”[MeSH Terms] OR ‘‘multiple”[All Fields] AND ‘‘sclerosis”[All Fields] OR ‘‘multiple sclerosis”[All Fields] AND ‘‘rehabilitation”[Subheading] OR ‘‘rehabilitation”[All Fields] OR ‘‘rehabilitation”[MeSH Terms]. We have only selected texts in English and removed duplicates. All articles have been evaluated according to the title, abstracts and text. We included studies that examined VR in MS patients, excluding studies with patients who had a psychiatric history. 3. VR and cognitive impairment in MS Cognitive dysfunction (CD) is a common feature in patients with MS. It affects 65% of patients, and may be present both during the initial stages of the disease and in the phases of severe disability [21,22]. In MS patients, CD may have a significant negative impact on quality of life and increasing caregiver burden, activities of daily living, and independence [23–25]. The most frequent neuropsychological symptoms include deficit in executive functions,
Table 1 Shows the main studies concerning the effects of virtual reality training in people with multiple sclerosis. Study
Design
Patients
Major findings
Russo M at al. 2018
Explorative Study
The study provides evidence that robotic rehabilitation coupled with two-dimensional VR may be a valuable tool in promoting functional recovery in patients with MS.
Stratton ME et al. 2015
Eftekharsadat B et al., 2015
Explorative Study Explorative Study Explorative Study Explorative Study Explorative Study Pilot Study
45 patients randomized into CG or EG 26 EG 19 CG 56 MS patients
Thomas S et al. 2014
Pilot Study
30 MS patients
Thomas S et al. 2017
Pilot Study
30 MS patients
Leocani L et al., 2007 Jonsdottir J et al.
Pilot Study Pilot Study
Ortiz-Gutierrez R et al. 2013
Pilot Study
Kalron A et al. 2016
Pilot Study
Peruzzi A et al. 2016
Pilot Study
12 EG 10 EG 6 CG 25 EG 25 CG 16 EG 16 CG 8 EG
Prosperini L et al. 2013
Pilot Study
36 MS patients
Brichetto G et al., 2013
Pilot Study
36 MS patients
Calabrò RS et al., 2017
Pilot Study
34 MS patients
Lamargue-Hamel D et al. 2015
Pilot Study
30 MS patients
Robinson S et al. 2015 Gutiérrez RO et. Al. 2013 Behrendt F et al., 2018 Kramer A et al., 2014
25 EG 25 CG 75 patients (PD; MS; Stroke; TBI; GB) 70 MS patients 30 MS patients
VR environment can be a safe and useful tool to improve the ability to perform daily activities, such as street-crossing, in people with MS The study supports the use of Wii FitTM as an effective mean of balance and gait training for people with MS. The authors suggest that the VR program could be a valid and effective alternative to conventional therapy. The study examined the effectiveness of two new developed virtual software modules for the BMT training device. The authors observed that exergames seem to be an effective method to improve balance and gait in patients with MS. The study shows that the VR-based balance training program could improve the balance ability of patients with MS. The study showed that the home-intervention physiotherapist supported by the Wii device (Mii-vitaliSe) is effective in increasing the levels of activity in MS patients. The results suggest that the virtual reality instrument used (Mii-vitaliSe) is accepted by most of the participants and useful for the physiotherapists who provide it. The results show that VR training has promising results on short-term motor learning. The authors showed that serious games with VR are perceived positively by patients, and there have been significant improvements in the functionality of the arms. The study showed that patients have improved processing and integration of sensory information, with positive impact on motor outcomes. The study showed that VR-based balance training (CAREN) is an effective method of balance training for patients with MS. VR is feasible and safe for patients with MS with moderate disabilities, and can positively influence motor and cognitive aspects, such as dual tasking and obstacle negotiation. A home-based VR training could potentially provide a rehabilitation solution for effective, engaging balance for people with MS. The study highlights that interactive exercises with visual feedback, such as Wii, could be more effective than conventional treatment in improving balance disorders in MS. The authors showed that robotic rehabilitation combined with VR in patients with chronic hemiparesis promotes improved gait and balance. VR assessments are promising in identifying cognitive impairment in MS.
CG Control Group; EG Experimental Group; MS Multiple Sclerosis; VR Virtual Reality.
Please cite this article as: M. G. Maggio, M. Russo, M. F. Cuzzola et al., Virtual reality in multiple sclerosis rehabilitation: A review on cognitive and motor outcomes, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.03.017
M.G. Maggio et al. / Journal of Clinical Neuroscience xxx (xxxx) xxx
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Fig. 1. Shows the search strategy we used to select motor and cognitive studies in patients with MS.
working memory, visual-spatial abilities, and verbal fluency. These impairments are often associated with psychological disorders, such as anxiety and depression. To date, despite the intense research to understand the pathophysiology of MS no effective pharmacological treatment to improve or delay cognitive decline in MS has been established [26–29]. Neurobehavioral interventions using CR have shown favorable effects on the cognitive performance of MS patients and other related skills and, in some cases, have succeeded in generalizing these positive effects on the functioning capacity of an individual’s daily life [30–32]. For this reason, among the methods used for rehabilitation, a promising tool is VR [33–35]. Leocani et al. found impaired motor learning in MS patients for task features requiring a more complex integration of visual and sensory-motor information, such as moving in the depth planes (patients, using their right arms, with the wrist and right index finger extended, had to track a target object projected on the screen), and they showed a significant motor learning also after a single training session of interactive VR rehabilitative system in 12 patients [36]. Other studies have confirmed the important role of VR in cognitive rehabilitation in patients with MS [37,38]. Gaming through virtual scenarios is already being used in neurorehabilitation. Two distinctive approaches exist: i) gaming through serious games, which refers to games that are conceived and developed with the expressed purpose of being rehabilitative of a limited function; and ii) gaming through exergames that refers to the use of games already existing as entertainment for the general population but then applied in the context of rehabilitation [37,38]. According to two recent reviews on interactive gaming technology, serious and exergaming could both be promising approaches to facilitate rehabilitation of patients affected by MS. The study by Jonsdottir et al. involved 16 persons with MS (10 participants used a serious games platform, i.e. Rehab@Home, while 6
participants played with the Wii platform) [37–39]. Serious games were perceived positively in terms of user experience and motivation. However, only the exergaming group perceived a beneficial impact on their health [19]. Peruzzi et al. observed that VR is feasible and safe for patients with MS with moderate disabilities and can positively influence motor and cognitive aspects, such as dual tasking and obstacle negotiation [40]. Indeed, Lamargue-Hamel et al. have carried out a study with 30 MS individuals with a moderate cognitive impairment, demonstrating how assessment of deficits in a VR environment (Urban DailyCogÒ) was promising to identify the cognitive decline [20]. Moreover, Stratton et al. highlighted that the VR environment can be a safe and useful tool for employing the ability to perform daily activities, such as streetcrossing, in people with MS [41].
4. VR and motor dysfunction in MS Motor impairment is the most common symptom in multiple sclerosis (MS). Indeed, gait, coordination, and balance may be severely compromised, with considerable consequences on the patient’s daily living activities and psychological status [17]. Ambulation may be compromised early, even in people with mild disability, independently of the relapsing or progressive onset [42]. Specific gait abnormalities in ambulatory MS patients include reduced velocity and stride length, increased double-limb support time, and gait asymmetries. Balance impairment is frequently observed in people with MS and is considered to be one of the most disabling symptoms because it reduces mobility and independence, and affects overall quality of life [43]. Impaired balance and gait has also been associated with increased risk of falling [44]. Thus, a variety of new rehabilitative strategies have been
Please cite this article as: M. G. Maggio, M. Russo, M. F. Cuzzola et al., Virtual reality in multiple sclerosis rehabilitation: A review on cognitive and motor outcomes, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.03.017
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implemented showing their effectiveness. Moreover, specific rehabilitation programs for balance and gait improvement have shown small but significant effects in this population [3]. In recent years, the effectiveness of VR as a therapeutic tool has become an interesting topic of research in neurorehabilitation [45]. From a motor learning approach, VR offers the possibility of high intensity, task-oriented, multisensorial feedback training and represents a valid tool to promote visual, auditory and tactile input, and to strengthen feedback about performance [46]. VR provides immediate feedback to performance, thus assisting with the learning of new motor strategies of movement [47]. Moreover, VR is thought to entrain mirror neuron system thanks to the visuo-motor information coming from the virtual ‘‘scenarios”, such information recall stored motor plans, thus contributing to potentiate the motor performance [17]. Despite these evidences, the clinical effectiveness of VR for balance and gait training in multiple sclerosis remains unclear. Concerning this topic, only two bibliographic reviews focusing on general motor rehabilitation benefits have been published [48,49]. Most of the interventions consisted in a one-to-one tailored training regime supervised by a physiotherapist [50,51]. Two home-based interventions and one intervention based on telerehabilitation were also included [34,47,51]. Longterm effects were only assessed in one study [34]. However, when VR balance training was compared with conventional training, significant differences were only observed in two studies, and no differences between groups were reported in three studies [47–51]. Functional balance was only compared with no intervention in two studies and no significant differences were observed between the VR and control groups [54,55]. When VR training was compared with standard balance training, significant differences in balance improvements in favor of the VR group were found in two studies, [52,56]. while no differences between groups were reported by Lozano-Quilis et al. and Gutiérrez et al. [18–53]. Notably, a significant balance improvement after intervention only for the experimental group was demonstrated by Brichetto and coworkers [52]. Calabrò et al. showed that robotic rehabilitation combined with VR is an effective therapeutic option in MS patients with walking disability as compared to robotic gait training without VR. They demonstrated a greater improvement in balance in individuals undergoing VR, further supporting the idea of the VR pivotal role in motor rehabilitation of MS patients, maybe thanks to the involvement of mirror neuron system [17]. Moreover, Lokomat with VR may be useful in boosting motor recovery in MS patients undergoing traditional motor training [33]. Peruzzi and coworkers evaluated the effects of a rehabilitation intervention based on the combined use of VR and treadmill on gait of MS subjects (participants walked on the treadmill while watching a VR environment representing a tree-lined-trail), suggesting that intensive and progressive VR-based treadmill training program may be a viable approach in MS and may positively affect complex gait conditions, such as dual tasking and obstacle negotiation [40]. Regarding walking speed, no significant differences between groups were reported when VR was compared with standard gait therapy [18,53,58]. However, Peruzzi et al. observed significant walking speed improvements only in their VR training group [40]. Probably, considering that upper limb remains difficult to achieve, only one paper performed by Jonsdottir investigated the feasibility and showed preliminary evidence for efficacy of a serious games platform compared to exergaming using the Wii for arm rehabilitation in persons with MS. Sixteen patients with MS participated to the study: 10 participants used a serious-game platform (Rehab@Home), while 6 participants played with the commercial Wii platform, for four weeks (40 min, 12 sessions/4 weeks). Serious games were perceived positively in terms of user experience and motivation. There were clinically significant improvements in arm function in the serious games group, but
only the exergaming group perceived themselves as having improved their health [39].
5. Discussion The ineffectiveness or poor efficacy of pharmacological treatments on cognitive and motor disabilities in MS has highlighted the need for non-pharmacological interventions. Thus, neurorehabilitation programs are among the most popular therapies aimed at reducing the disabilities and social disadvantages that result from MS. Our results suggest that VR has additional benefits for cognitive and motor rehabilitation, especially when combined with other interventions. However, most studies presented poor methodologic quality and intervention programs lacked a clear rationale, in particular regarding treatment intensity, personalized training, and task variation. In addition, most studies were relatively small and without a comparison group. Generally, our results resemble several trials performed on other neurological populations such as stroke survivors, people with Parkinson’s disease, and elderly fallers [7–16]. To date, it is still undetermined as to which VR characteristics are most important for cognitive and/ or motor training and whether these effects are sustained over an extended period of time. Worth noting, due to the wide variety of VR rehabilitation systems, comparisons between studies are confusing and could be misleading. It is hypothesizable that VR provides the patient with multisensory feedbacks that can potentiate the use-dependent plasticity processes within the sensorymotor cortex, thus promoting/enhancing functional motor recovery. Furthermore, VR can increase patients’ motivation during rehabilitation by decreasing the perception of exertion, thus allowing patients to exercise more effortlessly and regularly. In virtual scenarios, it is possible to magnify the sense of presence by manipulating the characteristics of the VR, including screen size, duration of exposure, the realism of the presentation, and the use of animated avatar. About that, the use of an avatar may strengthen the use-dependent plastic changes within higher sensory-motor areas belonging to the mirror neuron system [57,38]. Indeed, the observation of an action, even simulated (on a screen, as in the case of VR), allows the recruitment of stored motor programs that would promote, in turn, movement execution recovery. It is important to note that commercial exergaming devices (considered in some studies as VR) do not allow scenario adjustments that in many cases are necessary to meet the physical abilities and treatment goals of the patient. In contrast, VR system training scenarios can be set up according to the patient’s abilities and progress during the intervention program. Additionally, VR training can be conducted in a controlled environment in order to regulate mechanical and visual cues. As such, rehabilitation outcomes may be specifically investigated without the risk of confounding variables. On the assumption that more engaging training might be more effective, combining cognitive VR training with others rehabilitative techniques should augment training efficacy, given the greater cognitive demands of combined physical and cognitive activity, particularly in a dual-tasking context, as it requires greater allocation of attention in healthy and neurologically impaired individuals [59–61].
6. Conclusions VR is a motivational and effective tool that could improve the traditional motor and cognitive rehabilitation for MS patients. The results of this narrative review showed that VR has positive effects in different cognitive and/or motor deficits. However, further larger sample studies are needed to investigate the real impact
Please cite this article as: M. G. Maggio, M. Russo, M. F. Cuzzola et al., Virtual reality in multiple sclerosis rehabilitation: A review on cognitive and motor outcomes, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.03.017
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Please cite this article as: M. G. Maggio, M. Russo, M. F. Cuzzola et al., Virtual reality in multiple sclerosis rehabilitation: A review on cognitive and motor outcomes, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.03.017
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Please cite this article as: M. G. Maggio, M. Russo, M. F. Cuzzola et al., Virtual reality in multiple sclerosis rehabilitation: A review on cognitive and motor outcomes, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.03.017
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Review article
Virtual reality in multiple sclerosis rehabilitation: A review on cognitive and motor outcomes Maria Grazia Maggio a, Margherita Russo b, Marilena Foti Cuzzola a, Massimo Destro a, Gianluca La Rosa a, Francesco Molonia a, Placido Bramanti a, Giuseppe Lombardo a, Rosaria De Luca a, Rocco Salvatore Calabrò a,⇑ a b
IRCCS Centro Neurolesi ‘‘Bonino Pulejo”, Messina, Italy U.O.C. Neurologia GOM Melacrino-Morelli-Bianchi, Reggio Calabria, Italy
a r t i c l e
i n f o
Article history: Received 26 January 2019 Accepted 11 March 2019 Available online xxxx Keywords: Cognitive rehabilitation Multiple sclerosis Virtual reality training
a b s t r a c t Multiple sclerosis (MS) is a demyelinating neurodegenerative disease with lesions involving the central nervous system. Clinical symptoms consist of disturbances in motor activity (e.g., weakness, spasticity, and tremor), sensory functioning (e.g., pain), visual functions (e.g., diplopia and optic neuritis), besides different cognitive (attention deficit and executive dysfunction) and behavioral abnormalities. This review aims to evaluate the role of VR tools in cognitive and motor rehabilitation of MS patients. Studies performed between 2010 and 2017 and fulfilling the selected criteria were searched on PubMed, Scopus, Cochrane and Web of Sciences databases, by combining the terms ‘‘VR rehabilitation” and ‘‘MS”. Our findings showed that, following the use of VR training, MS patients presented a significant improvement in motor (especially gait and balance) and cognitive function (with regard to executive and visual-spatial abilities, attention and memory skills). This review supports the idea that rehabilitation through new VR tools could positively affect MS patients’ outcomes, by boosting motivation and participation with a better response to treatment. Ó 2019 Elsevier Ltd. All rights reserved.
1. Introduction Multiple sclerosis (MS) is a demyelinating neurodegenerative disease with lesions involving the central nervous system. Indeed, the disease is largely caused by autoimmune processes that produce loss of myelin in the white matter of the cerebral hemispheres, brainstem, cerebellum, spinal cord, and optic nerves [1,2]. MS prevalence varies from 15/100.000 to 250/100.000, and it is estimated that two million people worldwide suffer from MS, and the disease is one of the most common causes of neurological disability in young adults [3]. The prevalence of MS in Italy estimates around 193 cases per 100.000 inhabitants, with the exception of Sardinia (360 cases for 100.000 inhabitants) [4]. The disease typical onset is around at 30 years, and is mostly diagnosed in women between 20 and 40 years. Clinically, most MS patients experience recurrent episodes (relapses) of neurological impairment, but in most cases (60% –80%), the course of the pathology becomes chronic and progressive with time, leading to cumulative ⇑ Corresponding author at: IRCCS Centro Neurolesi ‘‘Bonino-Pulejo”, S.S. 113, Contrada Casazza, 98124 Messina, Italy. E-mail address: [email protected] (R.S. Calabrò).
motor disability and cognitive deficits. MS presents a broad range of symptoms because of the widespread nature of the disease lesions within the CNS. Clinical symptoms consist of disturbances in motor activity (e.g., weakness, spasticity, and tremor), sensory functioning (e.g., pain), visual functions (e.g., diplopia and optic neuritis), besides different cognitive (attention deficit and executive dysfunction) and behavioral abnormalities [2,5,6]. MS therapy aims to slow down the course and treat the symptoms. The drugs used (immunosuppressants, immunomodulators, corticosteroids) are designed to shorten the relapse, reduce its severity and delay the progression of the disease. Instead, rehabilitation is oriented towards the re-education of motor and cognitive dysfunctions, and this is essential to favor the activities of daily life, permitting the strengthening of residual capacities and the learning of new strategies. The motor rehabilitation mainly used are conventional physiotherapy and kinesitherapy that reduce the difficulties related to spasticity, pain and fatigue. Furthermore, the conventional cognitive rehabilitation (CR) i.e. paper-pencil exercises, seems to be useful to increase cognitive abilities. In recent years, the use of VR has been introduced in the field of neurological rehabilitation, especially in patients with stroke, or Parkinson’s disease, and in children with cerebral palsy [7–11]. A recent study
https://doi.org/10.1016/j.jocn.2019.03.017 0967-5868/Ó 2019 Elsevier Ltd. All rights reserved.
Please cite this article as: M. G. Maggio, M. Russo, M. F. Cuzzola et al., Virtual reality in multiple sclerosis rehabilitation: A review on cognitive and motor outcomes, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.03.017
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performed by Doniger and colleagues showed the efficacy of a VRbased cognitive-motor training program on a cohort of patients affected by Alzheimer’s Disease [12]. In addition, a recent systematic review concerning computerized and VR cognitive training for individuals with mild cognitive impairment and dementia found consistent improvements in the cognitive domains of attention, executive function, and memory (visual and verbal), as well as significant reductions in depressive symptoms and anxiety, after these innovative interventions [13]. The use BTs-Nirvana on the recovery of cognitive and motor functions in stroke patients, using the Interactive-Semi-Immersive scenarios, has been proven to be effective, especially regarding attention and visual-spatial deficits, besides trunk control [14–16]. The role of VR as rehabilitative tool in MS patients is still under debate. Many studies have confirmed the important role of VR in both motor and cognitive rehabilitation (CR) [17–20]. The virtual interactive experience increases the self-efficacy of the subject affected by MS, and it can play an active role in similar environments with an increased knowledge and self-consciousness, and a higher self-consciousness in the environment and the development of the motor and cognitive components, as well as increasing the Motivation and the Interest [17–20]. Moreover, growing evidence in literature is supporting the idea of the pivotal role of VR coupled to robotic rehabilitation in improving motor and cognitive performances in MS patients [17]. In detail, Calabrò and coworkers showed not only a greater improvement in balance in individuals undergoing VR but also an improvement in the psychological outcomes, as shown by coping strategies improvement (Table 1).
This review aims to evaluate the role of VR in the rehabilitation of MS patients, with regard to motor and cognitive outcome. 2. Search strategy The studies were identified by searching on Scopus, PubMed, Web of Science, and Cochrane database all the studies fulfilling our selected criteria and published between 2007 and 2018 (see Fig. 1). The search combined the following terms: ‘‘virtual reality”[MeSH Terms] OR ‘‘virtual”[All Fields] AND ‘‘reality”[All Fields] OR ‘‘virtual reality”[All Fields] AND ‘‘multiple sclerosis”[MeSH Terms] OR ‘‘multiple”[All Fields] AND ‘‘sclerosis”[All Fields] OR ‘‘multiple sclerosis”[All Fields] AND ‘‘rehabilitation”[Subheading] OR ‘‘rehabilitation”[All Fields] OR ‘‘rehabilitation”[MeSH Terms]. We have only selected texts in English and removed duplicates. All articles have been evaluated according to the title, abstracts and text. We included studies that examined VR in MS patients, excluding studies with patients who had a psychiatric history. 3. VR and cognitive impairment in MS Cognitive dysfunction (CD) is a common feature in patients with MS. It affects 65% of patients, and may be present both during the initial stages of the disease and in the phases of severe disability [21,22]. In MS patients, CD may have a significant negative impact on quality of life and increasing caregiver burden, activities of daily living, and independence [23–25]. The most frequent neuropsychological symptoms include deficit in executive functions,
Table 1 Shows the main studies concerning the effects of virtual reality training in people with multiple sclerosis. Study
Design
Patients
Major findings
Russo M at al. 2018
Explorative Study
The study provides evidence that robotic rehabilitation coupled with two-dimensional VR may be a valuable tool in promoting functional recovery in patients with MS.
Stratton ME et al. 2015
Eftekharsadat B et al., 2015
Explorative Study Explorative Study Explorative Study Explorative Study Explorative Study Pilot Study
45 patients randomized into CG or EG 26 EG 19 CG 56 MS patients
Thomas S et al. 2014
Pilot Study
30 MS patients
Thomas S et al. 2017
Pilot Study
30 MS patients
Leocani L et al., 2007 Jonsdottir J et al.
Pilot Study Pilot Study
Ortiz-Gutierrez R et al. 2013
Pilot Study
Kalron A et al. 2016
Pilot Study
Peruzzi A et al. 2016
Pilot Study
12 EG 10 EG 6 CG 25 EG 25 CG 16 EG 16 CG 8 EG
Prosperini L et al. 2013
Pilot Study
36 MS patients
Brichetto G et al., 2013
Pilot Study
36 MS patients
Calabrò RS et al., 2017
Pilot Study
34 MS patients
Lamargue-Hamel D et al. 2015
Pilot Study
30 MS patients
Robinson S et al. 2015 Gutiérrez RO et. Al. 2013 Behrendt F et al., 2018 Kramer A et al., 2014
25 EG 25 CG 75 patients (PD; MS; Stroke; TBI; GB) 70 MS patients 30 MS patients
VR environment can be a safe and useful tool to improve the ability to perform daily activities, such as street-crossing, in people with MS The study supports the use of Wii FitTM as an effective mean of balance and gait training for people with MS. The authors suggest that the VR program could be a valid and effective alternative to conventional therapy. The study examined the effectiveness of two new developed virtual software modules for the BMT training device. The authors observed that exergames seem to be an effective method to improve balance and gait in patients with MS. The study shows that the VR-based balance training program could improve the balance ability of patients with MS. The study showed that the home-intervention physiotherapist supported by the Wii device (Mii-vitaliSe) is effective in increasing the levels of activity in MS patients. The results suggest that the virtual reality instrument used (Mii-vitaliSe) is accepted by most of the participants and useful for the physiotherapists who provide it. The results show that VR training has promising results on short-term motor learning. The authors showed that serious games with VR are perceived positively by patients, and there have been significant improvements in the functionality of the arms. The study showed that patients have improved processing and integration of sensory information, with positive impact on motor outcomes. The study showed that VR-based balance training (CAREN) is an effective method of balance training for patients with MS. VR is feasible and safe for patients with MS with moderate disabilities, and can positively influence motor and cognitive aspects, such as dual tasking and obstacle negotiation. A home-based VR training could potentially provide a rehabilitation solution for effective, engaging balance for people with MS. The study highlights that interactive exercises with visual feedback, such as Wii, could be more effective than conventional treatment in improving balance disorders in MS. The authors showed that robotic rehabilitation combined with VR in patients with chronic hemiparesis promotes improved gait and balance. VR assessments are promising in identifying cognitive impairment in MS.
CG Control Group; EG Experimental Group; MS Multiple Sclerosis; VR Virtual Reality.
Please cite this article as: M. G. Maggio, M. Russo, M. F. Cuzzola et al., Virtual reality in multiple sclerosis rehabilitation: A review on cognitive and motor outcomes, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.03.017
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Fig. 1. Shows the search strategy we used to select motor and cognitive studies in patients with MS.
working memory, visual-spatial abilities, and verbal fluency. These impairments are often associated with psychological disorders, such as anxiety and depression. To date, despite the intense research to understand the pathophysiology of MS no effective pharmacological treatment to improve or delay cognitive decline in MS has been established [26–29]. Neurobehavioral interventions using CR have shown favorable effects on the cognitive performance of MS patients and other related skills and, in some cases, have succeeded in generalizing these positive effects on the functioning capacity of an individual’s daily life [30–32]. For this reason, among the methods used for rehabilitation, a promising tool is VR [33–35]. Leocani et al. found impaired motor learning in MS patients for task features requiring a more complex integration of visual and sensory-motor information, such as moving in the depth planes (patients, using their right arms, with the wrist and right index finger extended, had to track a target object projected on the screen), and they showed a significant motor learning also after a single training session of interactive VR rehabilitative system in 12 patients [36]. Other studies have confirmed the important role of VR in cognitive rehabilitation in patients with MS [37,38]. Gaming through virtual scenarios is already being used in neurorehabilitation. Two distinctive approaches exist: i) gaming through serious games, which refers to games that are conceived and developed with the expressed purpose of being rehabilitative of a limited function; and ii) gaming through exergames that refers to the use of games already existing as entertainment for the general population but then applied in the context of rehabilitation [37,38]. According to two recent reviews on interactive gaming technology, serious and exergaming could both be promising approaches to facilitate rehabilitation of patients affected by MS. The study by Jonsdottir et al. involved 16 persons with MS (10 participants used a serious games platform, i.e. Rehab@Home, while 6
participants played with the Wii platform) [37–39]. Serious games were perceived positively in terms of user experience and motivation. However, only the exergaming group perceived a beneficial impact on their health [19]. Peruzzi et al. observed that VR is feasible and safe for patients with MS with moderate disabilities and can positively influence motor and cognitive aspects, such as dual tasking and obstacle negotiation [40]. Indeed, Lamargue-Hamel et al. have carried out a study with 30 MS individuals with a moderate cognitive impairment, demonstrating how assessment of deficits in a VR environment (Urban DailyCogÒ) was promising to identify the cognitive decline [20]. Moreover, Stratton et al. highlighted that the VR environment can be a safe and useful tool for employing the ability to perform daily activities, such as streetcrossing, in people with MS [41].
4. VR and motor dysfunction in MS Motor impairment is the most common symptom in multiple sclerosis (MS). Indeed, gait, coordination, and balance may be severely compromised, with considerable consequences on the patient’s daily living activities and psychological status [17]. Ambulation may be compromised early, even in people with mild disability, independently of the relapsing or progressive onset [42]. Specific gait abnormalities in ambulatory MS patients include reduced velocity and stride length, increased double-limb support time, and gait asymmetries. Balance impairment is frequently observed in people with MS and is considered to be one of the most disabling symptoms because it reduces mobility and independence, and affects overall quality of life [43]. Impaired balance and gait has also been associated with increased risk of falling [44]. Thus, a variety of new rehabilitative strategies have been
Please cite this article as: M. G. Maggio, M. Russo, M. F. Cuzzola et al., Virtual reality in multiple sclerosis rehabilitation: A review on cognitive and motor outcomes, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.03.017
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implemented showing their effectiveness. Moreover, specific rehabilitation programs for balance and gait improvement have shown small but significant effects in this population [3]. In recent years, the effectiveness of VR as a therapeutic tool has become an interesting topic of research in neurorehabilitation [45]. From a motor learning approach, VR offers the possibility of high intensity, task-oriented, multisensorial feedback training and represents a valid tool to promote visual, auditory and tactile input, and to strengthen feedback about performance [46]. VR provides immediate feedback to performance, thus assisting with the learning of new motor strategies of movement [47]. Moreover, VR is thought to entrain mirror neuron system thanks to the visuo-motor information coming from the virtual ‘‘scenarios”, such information recall stored motor plans, thus contributing to potentiate the motor performance [17]. Despite these evidences, the clinical effectiveness of VR for balance and gait training in multiple sclerosis remains unclear. Concerning this topic, only two bibliographic reviews focusing on general motor rehabilitation benefits have been published [48,49]. Most of the interventions consisted in a one-to-one tailored training regime supervised by a physiotherapist [50,51]. Two home-based interventions and one intervention based on telerehabilitation were also included [34,47,51]. Longterm effects were only assessed in one study [34]. However, when VR balance training was compared with conventional training, significant differences were only observed in two studies, and no differences between groups were reported in three studies [47–51]. Functional balance was only compared with no intervention in two studies and no significant differences were observed between the VR and control groups [54,55]. When VR training was compared with standard balance training, significant differences in balance improvements in favor of the VR group were found in two studies, [52,56]. while no differences between groups were reported by Lozano-Quilis et al. and Gutiérrez et al. [18–53]. Notably, a significant balance improvement after intervention only for the experimental group was demonstrated by Brichetto and coworkers [52]. Calabrò et al. showed that robotic rehabilitation combined with VR is an effective therapeutic option in MS patients with walking disability as compared to robotic gait training without VR. They demonstrated a greater improvement in balance in individuals undergoing VR, further supporting the idea of the VR pivotal role in motor rehabilitation of MS patients, maybe thanks to the involvement of mirror neuron system [17]. Moreover, Lokomat with VR may be useful in boosting motor recovery in MS patients undergoing traditional motor training [33]. Peruzzi and coworkers evaluated the effects of a rehabilitation intervention based on the combined use of VR and treadmill on gait of MS subjects (participants walked on the treadmill while watching a VR environment representing a tree-lined-trail), suggesting that intensive and progressive VR-based treadmill training program may be a viable approach in MS and may positively affect complex gait conditions, such as dual tasking and obstacle negotiation [40]. Regarding walking speed, no significant differences between groups were reported when VR was compared with standard gait therapy [18,53,58]. However, Peruzzi et al. observed significant walking speed improvements only in their VR training group [40]. Probably, considering that upper limb remains difficult to achieve, only one paper performed by Jonsdottir investigated the feasibility and showed preliminary evidence for efficacy of a serious games platform compared to exergaming using the Wii for arm rehabilitation in persons with MS. Sixteen patients with MS participated to the study: 10 participants used a serious-game platform (Rehab@Home), while 6 participants played with the commercial Wii platform, for four weeks (40 min, 12 sessions/4 weeks). Serious games were perceived positively in terms of user experience and motivation. There were clinically significant improvements in arm function in the serious games group, but
only the exergaming group perceived themselves as having improved their health [39].
5. Discussion The ineffectiveness or poor efficacy of pharmacological treatments on cognitive and motor disabilities in MS has highlighted the need for non-pharmacological interventions. Thus, neurorehabilitation programs are among the most popular therapies aimed at reducing the disabilities and social disadvantages that result from MS. Our results suggest that VR has additional benefits for cognitive and motor rehabilitation, especially when combined with other interventions. However, most studies presented poor methodologic quality and intervention programs lacked a clear rationale, in particular regarding treatment intensity, personalized training, and task variation. In addition, most studies were relatively small and without a comparison group. Generally, our results resemble several trials performed on other neurological populations such as stroke survivors, people with Parkinson’s disease, and elderly fallers [7–16]. To date, it is still undetermined as to which VR characteristics are most important for cognitive and/ or motor training and whether these effects are sustained over an extended period of time. Worth noting, due to the wide variety of VR rehabilitation systems, comparisons between studies are confusing and could be misleading. It is hypothesizable that VR provides the patient with multisensory feedbacks that can potentiate the use-dependent plasticity processes within the sensorymotor cortex, thus promoting/enhancing functional motor recovery. Furthermore, VR can increase patients’ motivation during rehabilitation by decreasing the perception of exertion, thus allowing patients to exercise more effortlessly and regularly. In virtual scenarios, it is possible to magnify the sense of presence by manipulating the characteristics of the VR, including screen size, duration of exposure, the realism of the presentation, and the use of animated avatar. About that, the use of an avatar may strengthen the use-dependent plastic changes within higher sensory-motor areas belonging to the mirror neuron system [57,38]. Indeed, the observation of an action, even simulated (on a screen, as in the case of VR), allows the recruitment of stored motor programs that would promote, in turn, movement execution recovery. It is important to note that commercial exergaming devices (considered in some studies as VR) do not allow scenario adjustments that in many cases are necessary to meet the physical abilities and treatment goals of the patient. In contrast, VR system training scenarios can be set up according to the patient’s abilities and progress during the intervention program. Additionally, VR training can be conducted in a controlled environment in order to regulate mechanical and visual cues. As such, rehabilitation outcomes may be specifically investigated without the risk of confounding variables. On the assumption that more engaging training might be more effective, combining cognitive VR training with others rehabilitative techniques should augment training efficacy, given the greater cognitive demands of combined physical and cognitive activity, particularly in a dual-tasking context, as it requires greater allocation of attention in healthy and neurologically impaired individuals [59–61].
6. Conclusions VR is a motivational and effective tool that could improve the traditional motor and cognitive rehabilitation for MS patients. The results of this narrative review showed that VR has positive effects in different cognitive and/or motor deficits. However, further larger sample studies are needed to investigate the real impact
Please cite this article as: M. G. Maggio, M. Russo, M. F. Cuzzola et al., Virtual reality in multiple sclerosis rehabilitation: A review on cognitive and motor outcomes, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.03.017
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Please cite this article as: M. G. Maggio, M. Russo, M. F. Cuzzola et al., Virtual reality in multiple sclerosis rehabilitation: A review on cognitive and motor outcomes, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.03.017
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Please cite this article as: M. G. Maggio, M. Russo, M. F. Cuzzola et al., Virtual reality in multiple sclerosis rehabilitation: A review on cognitive and motor outcomes, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.03.017