https://doi.org/10.1177/1073858417737486 The Neuroscientist 1–17 © The Author(s) 2017 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1073858417737486 journals.sagepub.com/home/nro Review Introduction In Europe every year, more than 1.5 million people suffer a stroke (World Health Organization, 2016). Despite con- siderable improvement in primary prevention, diagnostic workup, and treatment, such as stroke units, thrombolysis and thrombectomy, stroke still remains second or third place on the mortality list. Projections indicate that stroke events in European Union countries are likely to increase by 30% between 2000 and 2025 (Truelsen and others 2006). The overall global burden of stroke, in terms of functional, psychological, social, and also socioeconomic impact, is reaching epidemic proportions in Western industrialized countries (Feigin and others 2017). In fact, stroke is the leading cause of disability in the adult population with 25% to 30% of patients younger than 55 years (Smajlovic 2015). Even though acute stroke care and intensive rehabilitation have significantly improved, two-thirds of stroke survivors have to cope with persisting neurologic deficits and less than 20% of the patients are able to go back to their normal professional and private life (Di Carlo 2009). The most common impairments after stroke are motor deficits, such as hemiparesis of the contralateral limb, affecting more than 80% of stroke survivors and more than 40% of the patients in the chronic stage (Lee and others 2015). Upper extremity motor deficiencies include muscle weakness, changes in muscle tone (spasticity), joint contrac- ture, laxity, or impaired motor control. These impairments affect common daily-life activities such as reaching, picking up objects, holding onto objects or using tools such as a cell phone (Lang and others 2013). The main clinical predictor of whether a patient comes back to work or not is the degree of upper extremity function (Coupar and others 2012). 737486NRO XX X 10.1177/1073858417737486The NeuroscientistRaffn and Hummel review-article 2017 1 Defitech Chair of Clinical Neuroengineering, Center for Neuroprosthetics (CNP) and Brain Mind Institute (BMI), Swiss Federal Institute of Technology (EPFL), Geneva, Switzerland 2 Defitech Chair of Clinical Neuroengineering, Center for Neuroprosthetics (CNP) and Brain Mind Institute (BMI), Swiss Federal Institute of Technology (EPFL Valais), Clinique Romande de Réadaptation, Sion, Switzerland 3 Clinical Neuroscience, University of Geneva Medical School, Geneva, Switzerland Corresponding Author: Friedhelm Hummel, Defitech Chair of Clinical Neuroengineering, Center for Neuroprosthetics (CNP), Swiss Federal Institute of Technology (EPFL), Campus Biotech, Room H4.3.132.084, 9, Chemin des Mines, 1202 Geneva, Switzerland. Email: friedhelm.hummel@epfl.ch Restoring Motor Functions After Stroke: Multiple Approaches and Opportunities Estelle Raffin 1,2 and Friedhelm C. Hummel 1,2,3 Abstract More than 1.5 million people suffer a stroke in Europe per year and more than 70% of stroke survivors experience limited functional recovery of their upper limb, resulting in diminished quality of life. Therefore, interventions to address upper-limb impairment are a priority for stroke survivors and clinicians. While a significant body of evidence supports the use of conventional treatments, such as intensive motor training or constraint-induced movement therapy, the limited and heterogeneous improvements they allow are, for most patients, usually not sufficient to return to full autonomy. Various innovative neurorehabilitation strategies are emerging in order to enhance beneficial plasticity and improve motor recovery. Among them, robotic technologies, brain-computer interfaces, or noninvasive brain stimulation (NIBS) are showing encouraging results. These innovative interventions, such as NIBS, will only provide maximized effects, if the field moves away from the “one-fits all” approach toward a “patient-tailored” approach. After summarizing the most commonly used rehabilitation approaches, we will focus on NIBS and highlight the factors that limit its widespread use in clinical settings. Subsequently, we will propose potential biomarkers that might help to stratify stroke patients in order to identify the individualized optimal therapy. We will discuss future methodological developments, which could open new avenues for poststroke rehabilitation, toward more patient-tailored precision medicine approaches and pathophysiologically motivated strategies. Keywords neuroplasticity, brain stimulation, neurorehabilitation, precision medicine, stroke recovery