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 IRCCS Centro Neurolesi ‘‘Bonino Pulejo”, Messina, Italy b U.O.C. Neurologia GOM Melacrino-Morelli-Bianchi, Reggio Calabria, Italy article info Article history: Received 26 January 2019 Accepted 11 March 2019 Available online xxxx Keywords: Cognitive rehabilitation Multiple sclerosis Virtual reality training abstract 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 partic- ipation 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 pro- duce loss of myelin in the white matter of the cerebral hemi- spheres, 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 neurolog- ical 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 impair- ment, but in most cases (60% –80%), the course of the pathology becomes chronic and progressive with time, leading to cumulative 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 execu- tive 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 conven- tional 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. ⇑ Corresponding author at: IRCCS Centro Neurolesi ‘‘Bonino-Pulejo”, S.S. 113, Contrada Casazza, 98124 Messina, Italy. E-mail address: salbro77@tiscali.it (R.S. Calabrò). Journal of Clinical Neuroscience xxx (xxxx) xxx Contents lists available at ScienceDirect Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn 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