Participants
An electrode cuff for FES of the peroneal nerve (ActiGait®, ©Ottobock) was implanted in two patients suffering from foot drop secondary to MS. Approval by the local ethical review committee and informed consent regarding off-label use of the device was obtained beforehand.
Patient 1
Patient 1 was a 53-year-old lady who was diagnosed with MS in 2002 after developing right-sided hemihypesthesia, and followed a relapsing-remitting course. In retrospect, a transient sensory disturbance caudal from dermatome T10 in 1992 was in fact the first episode. A further episode, involving numbness of the right foot, followed in 2002. A slowly advancing, persistent mild paresis of the left leg affecting dorsiflexion and eversion of the foot began in December 2005. Ankle-twisting with increasing walking distance limited her walking distance to 500 m. The patient also suffered from temporary episodes of general fatigue. The disease evolved into a progressive course without further symptom remission. The Expanded Disability Status Scale (EDSS) [13] score was 3.5/10. The diagnosis of MS was supported by cerebral MRI lesions and delayed somatosensory evoked potentials (SSEP).
Immunomodulatory treatment with Interferon beta-1a (Avonex, Biogen Idec) was administered from 2003–2013, then discontinued following 8 years without exacerbations and increasing needle phobia. Symptomatic treatment of gait disturbance with Fampridine retard 2x 10 mg (Fampyra, Biogen Idec) from 2011 led to a more fluent gait pattern and facilitated stair climbing. Despite weekly physiotherapy, the drop foot remained impairing and walking distance did not improve. Because the movement limitations were only debilitating over longer distances, an AFO or other walking aid were not deemed to offer benefits outweighing their inconvenience.
At referral in April 2013, walking required considerable concentration, with frequent stumbling due to forefoot catching and ankle twisting, especially with increasing walking distance. After walking 500 m, the patient suffered from left leg pain. Neurological examination of motor skills revealed a mild distal left hemiparesis, particularly of the lower limb, with mild spasticity. The passive dorsiflexion/plantar flexion range exceeded 30° with a leg-foot-angle of approximately 90° in maximum passive dorsiflexion in a stretched leg position. Muscle strength in the left leg, rated according to the British Medical Research Council (BMRC) criteria, was as follows: hip flexion 4/5, knee flexion 4/5, other proximal movements 5/5, ankle dorsiflexion 1/5, pronation 2/5, supination 4/5, plantar flexion 5/5. Sensory system examination revealed hypesthesia of the left lower leg and foot, with pallhypesthesia of 5/8 over the left and 8/8 over the right malleolus, measured using a Rydel Seiffer tuning fork, Position-, temperature- and pain sensation were intact. Her gait pattern was spastic-ataxic but narrow-based. The outer edge of the foot dropped during the swing phase, with the forefoot dragging over the floor with increasing walking distance. Mild spasticity of the toes was present, with minimal ankle joint instability and the gait was asymmetrical.
A four-week test phase with surface FES increased walking distance and reduced effort on walking, but sensory side-effects were not well-tolerated. We therefore implanted an electrode cuff for FES of the left peroneal nerve (ActiGait®, ©Ottobock) in September 2013. There were no peri- or post-operative complications. After a healing phase of 3 weeks, we activated the stimulation system.
Patient 2
Patient 2 was a 46-year-old man, diagnosed with MS with a primary progressive course in 2007. He developed a slowly deteriorating paresis of the right leg with a disabling paresis of dorsiflexion (EDSS 6.5). With hindsight, the first symptoms appeared in 1998, with right upper limb weakness and numbness. Also of note is a spinal disc herniation of lumbar disc 4/5 to the right side, surgically treated in 2008.
On initial presentation in 03/2013, he reported a walking distance-dependent physical fatigue with increasing right leg weakness and forefoot catching, with concomitant back, sacral, and pelvic pain. Concentration was necessary to avoid stumbling, and he required a cane and an AFO as walking aids. Fatigue limited walking distance to 50 m using the AFO, and he was unable to walk without the AFO due to ankle twisting with each step.
Clinical examination revealed mild right hemiparesis and moderate lower limb spasticity with contracture of the calcaneal tendon. Passive dorsiflexion/plantar flexion range exceeded 30°, with a leg-foot-angle of approximately 90° on maximum passive dorsiflexion in a stretched leg position. Muscle strength in the right leg, according to BMRC criteria, was as follows: hip flexion 3/5, extension 4+/5, abduction and adduction 5/5, knee flexion 2/5, extension 5/5, ankle dorsiflexion 1/5, pronation and supination 2/5, plantar flexion 4+/5. Sensory examination revealed no sensory deficits in the lower limbs. His gait pattern was spastic-ataxic with circumduction of the right leg, initial forefoot-floor-contact, and dropping of the forefoot and outer edge during the swing phase. After a few steps, he began to drag his right leg, followed by the onset of spasticity of the toes and instability in the ankle and knee joints. As for Patient 1, MRI and electrophysiological findings supported the diagnosis of MS.
Immunomodulatory therapy was conducted with Interferon beta-1b 0.25 mg/ml (Betaferon, Bayer Health Care) every other day from diagnosis. He received no antispastic treatment. A temporary treatment with Fampridine retard 2x 10 mg (Fampyra, Biogen Idec) did not improve walking with the cane and AFO.
Although we observed a clinical benefit following a 4-week test phase with surface FES, the patient experienced difficulties with exact electrode positioning, and moreover, the electrodes were easily dislodged during walking. Surface FES was therefore deemed unsuitable for daily use, resulting in the decision to employ an implanted FES system for direct stimulation of the right peroneal nerve. We implanted the ActiGait® system in November 2013 without complications and activated it 5 weeks later.
FES system
ActiGait® (©Ottobock) is a semi-implantable closed-loop FES system generating dorsiflexion in drop foot (see Fig. 1). The system is adapted to individual gait phase and velocity by registering the patient’s heel lift through an externally placed heel switch. The control unit worn around the patient’s waist receives this trigger signal wirelessly and generates a variable electromagnetic field in the coiled antenna, which is connected to it. Transcutaneous electromagnetic induction is used to transfer the power and control signals to the implanted stimulator, which generates the stimulation pulses in 4 independent current sources. These impulses are then delivered through a dual lumen cable to 4 circularly arranged sets of electrodes embedded within a 23 mm silicone cuff. Each of the 4 channels can be controlled independently of the other channels, thus enabling the programmer to control the volume of tissue activated within the nerve. The fascicles of the common peroneal nerve can thus be selectively stimulated to trigger a balanced dorsiflexion of the foot while avoiding stimulation of sensory fascicles.
Assessment tools
Evaluation of gait symmetry, comprising walking distance measurement and gait velocity, as well as quality of life (QoL), using the SF-36 questionnaire [14], were performed before implantation of the electrode, after the stimulation was first commenced (referred to as “activation day”), and again 3 months later.
We used the 3D-Kinematicsystem from “Vicon Motion Systems, Oxford UK” to capture the kinematics, required for gait velocity measurement and for calculation of the patient’s center of mass to quantify gait symmetry. Markers were placed on the head, trunk, and limbs in accordance with the Plug-In Gait software package, which corresponds with the clinical gold standard in gait analysis. To avoid inclusion of acceleration and braking phases in the gait velocity measurements, the walking space provided for patients had a total length of 8 meters, suitable for recording a walking distance of at least 4 meters. In order to maintain balance with an asymmetric gait, trunk, limb and head movements may be employed, stabilizing the gait by shifting the center of mass [15]. The change in gait resulting from stimulation can be quantified by calculating the shift in the patient’s center of mass after stimulation. The motion capture system allows the patient’s center of mass to be calculated, based on the position locations of the markers in 3-D space, thus providing a holistic view of the body as a single moving system in equilibrium in the transverse plane [16] and thereby a measurement of the effect of the stimulation on gait. Total walking distance in meters was measured in the clinic corridor. The patients were asked to walk until they no longer felt able to continue. Gait velocity was defined as speed over a distance of 10 meters, measured three times with and without stimulation. Both examinations took place on different days to avoid bias of results by fatigue. Gait velocity and gait analysis were performed successively with a pause of at least 30 min for recovery.
Statistics
T-tests were applied to provide a quantitative indicator of the significance of the changes in the assessment measures following stimulation treatment. The two measurements of walking distance on activation day, first without, then during stimulation, were compared with the two measurements performed 3 months later. The three measurements of gait velocity performed on activation day before stimulation was commenced were compared with three measurements made 3 months later during stimulation. The difference between these values reflects both the efficacy of the device and the improvement made over the time of its use. Simulation supports the validity of T-tests with low sample numbers, defined as N = 2 to 5. [17]. The QoL questionnaire, completed before stimulation commencement and repeated following 3 months of stimulation treatment, consists of 36 items, each rated on a scale from 0 to 100. In order to provide an indication of whether QoL was generally improved following treatment, each of the 36 items was taken as a separate indicator, providing 35° of freedom.
We measured the maximum deviations of center of mass to each side from the midline for each gait cycle pre-operatively and 3 months post-operatively. For Patient 1, two gait cycles were completed at each assessment (N = 4, including both sides), and Patient 2 completed 3 gait cycles (N = 6, including each side). The absolute difference between the two sets of distance measures was subjected to a T-test of the null hypothesis that the deviations from the midline post-operatively did not differ from those measured pre-operatively.