Neurotechnology-aided Interventions for Upper Limb Motor Rehabilitation in Severe Chronic Stroke

Martina Coscia; Maximilian J. Wessel; Ujwal Chaudary; José del R. Millán; Silvestro Micera; Adrian Guggisberg; Philippe Vuadens; John Donoghue; Niels Birbaumer; Friedhelm C. Hummel


Brain. 2019;142(8):2182-2197. 

In This Article

Abstract and Introduction


Upper limb motor deficits in severe stroke survivors often remain unresolved over extended time periods. Novel neurotechnologies have the potential to significantly support upper limb motor restoration in severely impaired stroke individuals. Here, we review recent controlled clinical studies and reviews focusing on the mechanisms of action and effectiveness of single and combined technology-aided interventions for upper limb motor rehabilitation after stroke, including robotics, muscular electrical stimulation, brain stimulation and brain computer/machine interfaces. We aim at identifying possible guidance for the optimal use of these new technologies to enhance upper limb motor recovery especially in severe chronic stroke patients. We found that the current literature does not provide enough evidence to support strict guidelines, because of the variability of the procedures for each intervention and of the heterogeneity of the stroke population. The present results confirm that neurotechnology-aided upper limb rehabilitation is promising for severe chronic stroke patients, but the combination of interventions often lacks understanding of single intervention mechanisms of action, which may not reflect the summation of single intervention's effectiveness. Stroke rehabilitation is a long and complex process, and one single intervention administrated in a short time interval cannot have a large impact for motor recovery, especially in severely impaired patients. To design personalized interventions combining or proposing different interventions in sequence, it is necessary to have an excellent understanding of the mechanisms determining the effectiveness of a single treatment in this heterogeneous population of stroke patients. We encourage the identification of objective biomarkers for stroke recovery for patients' stratification and to tailor treatments. Furthermore, the advantage of longitudinal personalized trial designs compared to classical double-blind placebo-controlled clinical trials as the basis for precise personalized stroke rehabilitation medicine is discussed. Finally, we also promote the necessary conceptual change from 'one-suits-all' treatments within in-patient clinical rehabilitation set-ups towards personalized home-based treatment strategies, by adopting novel technologies merging rehabilitation and motor assistance, including implantable ones.


Stroke constitutes a major public health problem affecting millions of people worldwide with considerable impacts on socio-economics and health-related costs. It is the second cause of death (Langhorne et al., 2011), and the third cause of disability-adjusted life-years worldwide (Feigin et al., 2014): ~8.2 million people were affected by stroke in Europe in 2010, with a total cost of ~€64 billion per year (Olesen et al., 2012). Due to ageing societies, these numbers might still rise, estimated to increase 1.5–2-fold from 2010 to 2030 (Feigin et al., 2014).

Improving upper limb functioning is a major therapeutic target in stroke rehabilitation (Pollock et al., 2014; Veerbeek et al., 2017) to maximize patients' functional recovery and reduce long-term disability (Nichols-Larsen et al., 2005; Veerbeek et al., 2011; Pollock et al., 2014). Motor impairment of the upper limb occurs in 73–88% first time stroke survivors and in 55–75% of chronic stroke patients (Lawrence et al., 2001). Constraint-induced movement therapy (CIMT), but also standard occupational practice, virtual reality and brain stimulation-based interventions for sensory and motor impairments show positive rehabilitative effects in mildly and moderately impaired stroke victims (Pollock et al., 2014; Raffin and Hummel, 2018). However, stroke survivors with severe motor deficits are often excluded from these therapeutic approaches as their deficit does not allow easily rehabilitative motor training (e.g. CIMT), treatment effects are negligible and recovery unpredictable (Byblow et al., 2015; Wuwei et al., 2015; Buch et al., 2016; Guggisberg et al., 2017).

Recent neurotechnology-supported interventions offer the opportunity to deliver high-intensity motor training to stroke victims with severe motor impairments (Sivan et al., 2011). Robotics, muscular electrical stimulation, brain stimulation, brain computer/machine interfaces (BCI/BMI) can support upper limb motor restoration including hand and arm movements and induce neuro-plastic changes within the motor network (Mrachacz-Kersting et al., 2016; Biasiucci et al., 2018).

The main hurdle for an improvement of the status quo of stroke rehabilitation is the fragmentary knowledge about the physiological, psychological and social mechanisms, their interplay and how they impact on functional brain reorganization and stroke recovery. Positive stimulating and negatively blocking adaptive brain reorganization factors are insufficiently characterized except from some more or less trivial determinants, such as number and time of treatment sessions, pointing towards the more the better (Kwakkel et al., 1997). Even the long accepted model of detrimental interhemispheric inhibition of the overactive contralesional brain hemisphere on the ipsilesional hemisphere is based on an oversimplification and lack of differential knowledge and is thus called into question (Hummel et al., 2008; Krakauer and Carmichael, 2017; Morishita and Hummel, 2017).

Here, we take a pragmatic approach of comparing effectiveness data, keeping this lack of knowledge of mechanisms in mind and providing novel ideas towards precision medicine-based approaches to individually tailor treatments to the characteristics and needs of the individual patient with severe chronic stroke to maximize rehabilitative outcome.