Functional electrical stimulation through direct 4-channel nerve stimulation to improve gait in multiple sclerosis: a feasibility study

Multiple sclerosis (MS) is an autoimmune-mediated disorder leading to progressive neurodegeneration, with increasing disability in many patients despite modern treatment approaches. Although recent surveys have demonstrated the importance of walking for MS patients [1], gait dysfunction occurs in 80 % of all MS patients after a 10 to 15 year disease duration [2], often due to central paralysis of the lower limbs, and commonly involving a drop foot. Gait disturbances can lead to frequent falls [3] and a pathological compensatory gait [4]. Common treatment options such as walking aids, ankle foot orthoses (AFO) to prevent forefoot floor contact during the swing phase of walking, and pharmacological treatments (such as the potassium channel blocker fampridine and local or systemic antispastic therapy) show only limited efficacy, with benefits only in individual cases.

Functional electrical stimulation (FES) was first proposed in the 1960s as a stroke therapy [5]. It describes application of an electric current to a nerve in order to induce muscle contraction and thereby assist in performance of a functional activity such as walking. The ActiGait® System (details of the operation mode are described below) was officially approved in Germany in 2007 for hemiplegia following ischaemic or hemorrhagic stroke. Because the ActiGait System has been recently introduced, many studies investigating its use have not yet reached publication. We therefore enquired directly with Ottobock, who reported that the device has been implanted in approximately 400 post-stroke patients (effective July 2015), but that implantation for other indications remains rare.

Therapeutic success may be anticipated, however, in upper motor neuron damage regardless of etiology [6]. Moreover, benefits have been reported in MS patients either receiving surface FES [7–11] or by use of a 2-channel implanted system that stimulates the two branches of the common peroneal nerve [12]. Difficulties reported by some of our patients in handling a surface FES system, and sensory side-effects resulting from external attachment of the electrodes, led us to investigate whether the advantages offered by an implantable system could include reduced sensory side-effects. We provide here the first report of successful implementation of FES applied directly to the peroneal nerve via an implanted 4-channel cuff electrode to aid dorsiflexion in MS in two patients. Both patients, suffering from progressive disease and central drop foot, experienced considerable improvement in gait physiology, with significantly increased walking distance, as well as significant enhancement of quality of life (QoL).

Dropping of the forefoot in the swing phase of gait can cause stumbling and falling [18]. A central drop foot is often accompanied by ankle instability simply during standing, as well as in the stance phase of the gait, increasing the risk of the ankle twisting, as commonly observed clinically. Moreover, walking becomes effortful and slow, potentially shortening walking distance [19, 20]. Degenerative joint or back pain due to compensatory weight shift may develop in the long term, as observed in Patient 1.

Patients with drop foot often depend on walking aids such as an AFO, which acts passively as a cast. The main disadvantage in using an AFO is that it does not cause muscle contraction and can thus lead to further joint immobilization. It also lacks the sensory feedback of muscle contraction compared with FES. Moreover, spasticity of the toe flexors, as experienced by Patient 2, can cause pressure sores. FES via surface or implantable electrodes offers a means of compensating for these issues. The few studies reported evaluating implantable FES systems found improvements in gait parameters and QoL in post-stroke patients [21–23]. The ActiGait® system has been employed in a number of studies to date, and few adverse events have occurred [21, 24]. Although the motor response is similar using surface compared with implanted FES [12], the potential risks of surgery may be outweighed by several advantages offered by implanted over surface FES. Firstly, the electrode cuff, with its 4 channels placed circularly around the target nerve, generates the required motor response more precisely than surface stimulation. Because 4 potential channels are available for treatment, an optimum balance between dorsiflexion and eversion for the individual patient can be achieved. In some cases, for instance, a better orthotic effect, with greater ankle joint stability, can be obtained by distinct eversion. Secondly, the patient is not required to apply the electrode to the leg, which takes time, and moreover can be difficult to perform correctly, as reported by patient 2. The use of an implantable system could thus potentially lead to more consistent use of the device, with a concomitant increase in the therapeutic effect. Thirdly, discomfort due to electrical stimulation is minimal, because applying the current directly to the nerve avoids stimulation of non-target nerves, eliminating sensory side-effects, which cannot be achieved using a skin- mounted electrode. FES with an implantable multichannel system can therefore be more comfortable, as experienced by patient 1.

We provide here the first report of an implantable 4-channel FES system in patients with MS. A 2-channel system was implanted in 46 patients with central drop foot of mixed etiology, including 17 MS patients, and provided promising results, which have thus far been presented as preliminary findings [12]; gait performance improvement was similar to that provided in the same patients using a surface stimulation system. The method of fixation, however, whereby the electrode is sewn directly onto the nerve, resulted in considerable adverse effects, with temporary nerve dysfunction in 10 cases, implant failure in 6 cases, and one infection resulting in 4 explantations [12]. The authors report improved results with reduced sutures [12], and preliminary long-term findings were reported in a recent conference, whose proceedings are not yet available [25]. The benefits in terms of gait parameters, QoL, and fatigue reduction found in the few studies investigating surface FES in MS patients were similar to those reported in stroke studies [7–11]. Moreover, the approach compared favorably with the current gold standard of AFO, both in terms of subjective patient reporting and measureable outcomes of improved walking distance and gait symmetry. These findings are consistent with randomized controlled trials comparing AFO with implanted FES post-stroke that demonstrated comparable improvement in gait and QoL [26] as well as superiority of FES for obstacle avoidance [27].

Our patients demonstrate that implantable FES can lead to considerable improvements in gait parameters and QoL. Over the short 3-month observation period, the patients showed an orthotic effect as well as a rehabilitation benefit on walking distance, and increased walking distance impacted QoL considerably. The second patient was able to walk over 500 m with the stimulation system switched on, compared with 50 m before implantation, enabling the patient to walk outside the home and to resume employment. Both patients reported decreased pain, which may result from reduced abnormal joint loading due to pathological compensatory gait patterns and effort in ambulation. In patient 1, although the more balanced and centered gait pattern was observable clinically, the improvement in gait symmetry measurement was less marked than in patient 2. With temporospatial gait analysis, we sought to quantify our clinical observations using a readily measurable component of gait symmetry and found a small but nonetheless statistically significant reduction in drift of center of mass to each side. In patient 1, the increase in walking distance was the more pronounced improvement. In patient 2, the more marked reduction in drift is likely to be because this patient showed a more pronounced asymmetry of gait before the intervention. The difference in findings between these two patients, both of whom reported gait improvement following stimulation treatment, underlines the importance of using a range of outcome measures in quantitative outcome assessment.

Both patients experienced reduced fatigue despite being more active. Social factors also improved, possibly due to increased self-sufficiency and participation, resulting from increased mobility. The current standard therapy for drop foot is an AFO. Our second patient reported an improved walking experience over longer distances with FES in comparison with the AFO, resulting in increased walking distance and gait symmetry. Recent randomized controlled trials comparing AFO with FES, including both surface as well as implanted FES in post-stroke patients, showed FES to provide equivalent improvement in gait and QoL to AFO [26] and enhanced obstacle avoidance ability [27]. In another study, stroke patients evaluated surface FES in a structured interview as generally superior to different kinds of AFO [28], but MS patients only reported advantages from FES in terms of increased walking distance, fitness and physical activity [29]. These findings are consistent with the statements from our second patient, who used an AFO before receiving FES.

After 3 months using the FES, the second patient was able to walk a distance without technical assistance that he could only achieve with the use of an AFO pre-operatively. This improvement is consistent with findings using surface FES, which show that stimulation may lead to enhancement of motor cortex neuroplasticity [30]. It is moreover likely that the regular muscle contraction brought about during the use of the FES led to improvements in muscle strength, which do not occur when the ankle is held in a fixed position with an AFO.

The progressive character of MS may be considered as a critical difference between post-stroke and MS patients. However, patients who have suffered a stroke are recognized to be at risk of further cerebrovascular events due to the persistence of the underlying pathology, such as arteriosclerosis or atrial fibrillation. Even if a further episode leads to persisting or additional deficits, the patient may still benefit from assisted dorsiflexion of the foot. If motor function of the ipsilateral leg diminishes, ActiGait® allows adaptation of stimulation parameters, for example to increase the amplitude of dorsiflexion. Many MS patients also remain stable for long time periods due to new and effective immunomodulatory basis treatment [31], and may therefore also be suitable candidates to receive an implantable FES system. The disadvantages of surface over implantable FES, such as poor tolerance of sensory effects, and difficulties with electrode placement, thus support the use of implantable rather than surface FES, even in progressive disorders.

We conclude that implantable FES systems are a feasible new option for treating central foot drop in MS patients. We demonstrate improvements in gait parameters, and reduction of pain and fatigue, as well as positive changes in quality of life in two individuals suffering from progressive MS treated with an implantable device for FES of the peroneal nerve. The 4 channel cuff FES system appears to offer the recognized advantages of an implantable system compared with surface stimulation and moreover offers the possibility of achieving these benefits with fewer side-effects and complications than those encountered using a system in which the electrodes are sewn directly onto the nerve. The success of the therapy in this preliminary study paves the way for a larger trial to evaluate the benefits and general safety of the approach.