Open Access Study protocol

Impact of early applied upper limb stimulation: The EXPLICIT-stroke programme design

Gert Kwakkel14*, Carel GM Meskers2, Erwin E van Wegen1, Guus J Lankhorst1, Alexander CH Geurts3, Annet A van Kuijk3, Eline Lindeman4, Anne Visser-Meily45, Erwin de Vlugt6 and J Hans Arendzen2

Author Affiliations

1 Dept. Rehabilitation Medicine, VU University Medical Centre, PO Box 7057, 1007 MB, Amsterdam, The Netherlands

2 Dept. Rehabilitation Medicine, Leiden University Medical Centre, PO Box 9600, 2300 RC, Leiden, The Netherlands

3 Dept. Rehabilitation Medicine, Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands

4 Dept. Rehabilitation Medicine, University Medical Centre and Rudolf Magnus Institute of Neuroscience, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands

5 Rehabilitation Centre "De Hoogstraat", PO Box 85238, 3508 AE, Utrecht, The Netherlands

6 Department of Biomechanical Engineering, Faculty of Mechanical Engineering, Delft University of Technology, Mekelweg 2, 2628 CD, Delft, The Netherlands

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BMC Neurology 2008, 8:49  doi:10.1186/1471-2377-8-49

Published: 17 December 2008



Main claims of the literature are that functional recovery of the paretic upper limb is mainly defined within the first month post stroke and that rehabilitation services should preferably be applied intensively and in a task-oriented way within this particular time window. EXplaining PLastICITy after stroke (acronym EXPLICIT-stroke) aims to explore the underlying mechanisms of post stroke upper limb recovery. Two randomized single blinded trials form the core of the programme, investigating the effects of early modified Constraint-Induced Movement Therapy (modified CIMT) and EMG-triggered Neuro-Muscular Stimulation (EMG-NMS) in patients with respectively a favourable or poor probability for recovery of dexterity.


180 participants suffering from an acute, first-ever ischemic stroke will be recruited. Functional prognosis at the end of the first week post stroke is used to stratify patient into a poor prognosis group for upper limb recovery (N = 120, A2 project) and a group with a favourable prognosis (N = 60, A1 project). Both groups will be randomized to an experimental arm receiving respectively modified CIMT (favourable prognosis) or EMG-NMS (poor prognosis) for 3 weeks or to a control arm receiving usual care. Primary outcome variable will be the Action Research Arm Test (ARAT), assessed at 1,2,3,4,5, 8, 12 and 26 weeks post stroke. To study the impact of modified CIMT or EMG-NMS on stroke recovery mechanisms i.e. neuroplasticity, compensatory movements and upper limb neuromechanics, 60 patients randomly selected from projects A1 and A2 will undergo TMS, kinematical and haptic robotic measurements within a repeated measurement design. Additionally, 30 patients from the A1 project will undergo fMRI at baseline, 5 and 26 weeks post stroke.


EXPLICIT stroke is a 5 year translational research programme which main aim is to investigate the effects of early applied intensive intervention for regaining dexterity and to explore the underlying mechanisms that are involved in regaining upper limb function after stroke. EXPLICIT-stroke will provide an answer to the key question whether therapy induced improvements are due to either a reduction of basic motor impairment by neural repair i.e. restitution of function and/or the use of behavioural compensation strategies i.e. substitution of function.

EXPLICIT is registered at the Netherlands Trial Register (NTR, webcite., TC 1424)