Electrical somatosensory stimulation followed by motor training of the paretic upper limb in acute stroke: study protocol for a randomized controlled trial

Stroke is ranked as the third largest cause of disease burden globally [1], causing substantial physical, psychological and financial demands on patients, families, and societies at large [2‐4]. Upper limb paresis is one of the most frequent impairments following stroke and affects 48–77% of patients in the acute stroke phase [5‐7]. Moreover, upper limb paresis has been identified as a major obstacle to regaining independence in activities of daily living (ADLs) [8]. In fact, only 12–34% of the patients achieve full functional recovery of the affected upper limb at 6 months post stroke [9, 10]. This represents a considerable challenge since near complete functional recovery is required to routinely involve the affected upper limb in performing ADLs [11].

Recovery of upper limb functioning is typically pronounced during the first month and subsequently levels off by 6 months post stroke [12‐14]. Regaining hand dexterity (i.e., motor skills such as reaching, grasping, gripping, moving and releasing objects) is often achieved already within the first 4 weeks, implying that there may be a critical time window for recovery of upper limb functioning [9, 10] during which rehabilitation efforts may maximize functional recovery. However, there are few studies investigating the effect of motor rehabilitation methods in the initial weeks after stroke.

Electrical stimulation (ES) is one of the methods that have been used to facilitate recovery of upper limb functioning following stroke. ES can induce a muscle contraction, or it can be a somatosensory stimulation below the motor threshold [15]. The majority of studies using ES have been conducted in chronic stroke and, therefore, it remains unknown to what extent ES applied in the acute phase after stroke could affect the recovery of upper limb functioning. Also, these investigations have largely focused on ES that induces muscle contraction. In healthy persons, the application of low-intensity ES with no or small motor responses to peripheral hand nerves [16‐20], forearm muscles [21] or the whole hand [22, 23] elicits an increase in the cortical excitability of the representations that control the stimulated body parts, which seems to outlast the stimulation period itself [18, 21, 23]. It has been hypothesized that increasing the amount of somatosensory input may enhance the motor recovery of patients following stroke [24]. Recent data on acute, subacute and mostly chronic stroke patients suggest that a single 2-h session of ESS to the peripheral hand nerves leads to transient improvement of pinch force, movement kinematics and upper limb motor skills required for ADL performance [25‐31]. However, ESS was only used in conjunction with motor training in one of these studies [29]. Interestingly, there is some evidence that multiple sessions of ESS to the peripheral hand nerves, in conjunction with motor training, might improve motor skills of the paretic upper limb in subacute [32, 33] and chronic stroke patients [34], and, moreover, that these positive results seems to be long lasting [34]. However, the effect of ESS in conjunction with motor training has never been investigated in acute stroke patients. It is noteworthy that ESS is benign in nature, causes patients minimal discomfort and adverse effects (itch and blushing), is relatively inexpensive and can easily be incorporated into clinical practice [35]. Therefore, it would be valuable to establish the effect of multiple sessions of ESS in conjunction with motor training in the restoration of upper limb functioning in the acute stroke phase.

The purpose of the present trial is to investigate the effect of multiple sessions of ESS treatment accompanied by motor training on the recovery of the affected upper limb following stroke. The ESS treatment is initiated in the acute stroke phase and each ESS session is immediately followed by motor training of the paretic upper limb. Specifically, we wish to address the following:

Our hypothesis is that ESS treatment initiated in the acute stroke phase will improve paretic upper limb functioning as measured by the Box and Block Test (BBT) (primary outcome measure) at 6 months post stroke.

To our knowledge, this is the first trial investigating the effect of multiple sessions of ESS treatment in the acute stroke phase on the recovery of upper limb paresis. Several studies have shown that the process of upper limb recovery, and especially that of hand dexterity, is most pronounced during the first 4 weeks post stroke after which the recovery gradually levels off before reaching a plateau around 6 months post stroke. Therefore, initiation of rehabilitation in the early weeks post stroke may be essential for achieving successful upper limb recovery at the end of the rehabilitation process. Our trial intends to evaluate the effect of ESS – a rehabilitation method with the potential of applicability in clinical practice. ESS is easy to administer, inexpensive, free of patient discomfort and probably highly acceptable to frail patients in the early days post stroke.

Contrary to previous studies that primarily focused on the stimulation of the peripheral hand nerves at wrist level, we use two sets of large electrodes (see “Intervention” section) to stimulate somatosensory receptors in the shoulder, elbow and wrist regions. We believe that the larger area covered may be beneficial, but because we do not have a third trial arm receiving ESS at wrist level only, we will not be able to identify the effect of increasing the stimulation areas per se.

The eligibility criteria for participation in this trial are very broad. Basically, we include all adult stroke patients living in the hospital’s catchment area, except those with remaining upper limb paresis from a previous stroke, contraindications to ESS, severe prestroke disability or inability to provide informed consent. Based on this nonrestrictive participant selection, the results can be generalized to the larger population of patients with a first-ever stroke or successful recovery after a previous stroke and who present an upper limb paresis of varying degrees of severity. However, since our trial is not powered to perform subgroup analyses, we may encounter challenges in detecting the effect of ESS in such a heterogeneous sample. The possibility of overlooking a treatment effect on a specific subgroup of stroke patients (type II error) is a limitation of the study.

Designing the control ESS treatment was challenging since the intervention can be perceived by the trial participants who may also interact with each other during hospitalization. Since a completely inactive ESS treatment gave rise to concerns about high dropout rates in the control group, we designed a sham ESS treatment with an extremely low treatment dose. It is unlikely that the total amount of sham ESS treatment (1.2 min) is sufficient to induce any training effects. However, we are unable to verify this since we do not have a trial arm receiving completely inactive or no ESS. As a consequence, our trial results can be biased towards an underestimation of the effect of ESS treatment. It is noteworthy that both the control and the intervention group receive the same amount of attention from the personnel during the ESS sessions. Although some participants might figure out their group allocation, we hope that they would be motivated to continue in the trial due to fact that they are offered upper limb training in addition to the usual rehabilitation.

The recruitment of participants was initiated on 13 October 2014 and will continue until complete sample size is achieved which is expected in March 2017. At the submission time of this protocol article, patients are still being recruited for the trial.