Subcutaneous Stimulation as Add-on Therapy to Spinal Cord Stimulation in Patients With Persistent Spinal Pain Syndrome Significantly Increases the Total Electrical Charge per Second: Aspects on Stimulation Parameters and Energy Requirements of the Implanted Neurostimulators.

OBJECTIVE: In our previous multicenter randomized controlled trial, we demonstrated the clinical effectiveness of peripheral nerve field stimulation (PNFS) as add-on therapy to spinal cord stimulation (SCS) for the treatment of chronic back pain in patients with persistent spinal pain syndrome (PSPS) or failed back surgery syndrome (FBSS). To our knowledge, no previous study has investigated the effect of PNFS as an add-on to SCS on the energy consumption of the implanted neurostimulators. Therefore, in this study, we compared the specific stimulation parameters and energy requirements of a previously unreported group of patients with only SCS with those of a group of patients with SCS and add-on PNFS. We also investigated differences that might explain the need for PNFS in the treatment of chronic low back pain. MATERIALS AND METHODS: We analyzed 75 patients with complete sets of stimulation parameters, with 21 patients in the SCS-only group and 54 patients in the SCS + PNFS group. Outcome measures were average visual analog scale score, SCS parameters (voltage, frequency, and pulse width), SCS charge per second, and total charge per second. We analyzed baseline characteristics and differences between and within groups over time. RESULTS: Both groups had comparable patient characteristics at baseline and showed a significant decrease in back and leg pain. SCS charge per second did not significantly differ between the groups at baseline or at 12 months. The total charge per second was significantly higher in the active SCS + PNFS group than in the SCS-only group at baseline; in the SCS + PNFS group, this persisted for up to 12 months, and the SCS charge per second and total charge per second increased significantly over time. CONCLUSIONS: Our results show that add-on PNFS increases the total charge per second compared with SCS alone, as expected. However, further research is needed because our results do not directly explain why some patients require add-on PNFS to treat low back pain.

Spinal Cord Stimulation With Additional Peripheral Nerve/Field Stimulation Versus Spinal Cord Stimulation Alone on Back Pain and Quality of Life in Patients With Persistent Spinal Pain Syndrome.

INTRODUCTION: Persistent spinal pain syndrome (PSPS) or failed back surgery syndrome (FBSS) refers to new or persistent pain following spinal surgery for back or leg pain in a subset of patients. Spinal cord stimulation (SCS) is a neuromodulation technique that can be considered in patients with predominant leg pain refractory to conservative treatment. Patients with predominant low back pain benefit less from SCS. Another neuromodulation technique for treatment of chronic low back pain is subcutaneous stimulation or peripheral nerve field stimulation (PNFS). We investigated the effect of SCS with additional PNFS on pain and quality of life of patients with PSPS compared with that of SCS alone after 12 months. MATERIALS AND METHODS: This is a comparative study of patients with PSPS who responded to treatment with either SCS + PNFS or SCS only following a multicenter randomized clinical trial protocol. In total, 75 patients completed the 12-month follow-up: 21 in the SCS-only group and 54 in the SCS + PNFS group. Outcome measures were pain (visual analog scale), quality of life (36-Item Short Form Survey [SF-36]), anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), overall health (EuroQol Five-Dimension [EQ-5D]), disability (Oswestry Disability Index [ODI]), and pain assessed by the McGill questionnaire. RESULTS: There were no significant differences in baseline characteristics between the two groups. Both groups showed a significant reduction in back and leg pain at 12 months compared with baseline measurements. No significant differences were found between the groups in effect on both primary (pain) and secondary parameters (SF-36, HADS, EQ-5D, ODI, and McGill pain). CONCLUSION: In a subgroup of patients with chronic back and leg pain, SCS alone provided similar long-term pain relief and quality-of-life improvement as PNFS in addition to SCS. In patients with refractory low back pain not responding to SCS alone, adding PNFS should be recommended. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT01776749.

Evaluation of the Effectiveness of Percutaneous Octapolar Leads in Pain Treatment with Spinal Cord Stimulation of Patients with Failed Back Surgery Syndrome During a 1-Year Follow-Up: A Prospective Multicenter International Study.

OBJECTIVE: To evaluate the effectiveness and safety of percutaneous octapolar (8-contact) leads in spinal cord stimulation (SCS) treatment of failed back surgery syndrome (FBSS) patients who have not reached their therapy goals with other treatment interventions. METHODS: Our prospective, multicenter, open-label, nonrandomized study included 93 patients ≥ 18 years of age suffering from chronic (≥ 6 months), intractable pain predominantly in the legs. Patients implanted with octapolar lead(s) and a neurostimulator after a successful test trial were followed for 12 months. Patients provided self-reported data on change in visual analog scale (VAS) score for leg pain (primary outcome) and low back pain, quality of life (EuroQol 5 dimensions [EQ-5D] index), sleep, medication use, and paresthesia coverage (secondary outcomes). Adverse events and preferred stimulation settings were documented. RESULTS: Eighty-one (87%) patients had a successful SCS trial. Patients reported significantly improved leg pain relief; average VAS score was 72 ± 17 prior to SCS treatment and 32 ± 24 at 12 months (P < 0.001). Significant decrease in back pain (P < 0.001), improvement in quality of life (P < 0.001), and improvement in sleep (P < 0.05) was observed. Sixty-three percent and 40% of patients were responders (≥ 50% pain reduction) on leg and back pain, respectively, after 12 months. A decrease in medication use was seen for antidepressants and anticonvulsants. Eighty-eight percent of the patients managed with 1 or 2 programs for optimal effect and paresthesia coverage. Twenty-five SCS-related adverse events were registered in 22 patients (24%). Surgical revision due to lead displacement or dysfunction was needed in 6 (6%) of the patients. CONCLUSIONS: Use of percutaneous octapolar SCS leads gives significant long-term pain relief and improvement in quality of life and sleep in FBSS patients. The outcomes are better than reported on 4-contact leads and indicate that the progress in SCS technology that has taken place during the past decade correlates with therapy improvements.

Selectivity for specific cardiovascular effects of vagal nerve stimulation with a multi-contact electrode cuff.

The cardiovascular system can be influenced by electrically stimulating the vagal nerve. Selectivity for specific cardiac fibers may be limited when stimulating at the cervical level. Our objective was to increase effectiveness and selectivity for cardiovascular effects of vagal nerve stimulation by using local bipolar stimulation in one nerve cross section using a multi-contact cuff instead of less localized stimulation using a tripolar ring electrode. Both types of cuff electrodes were compared with respect to their relative effects on R-R interval (RRI), P-Q interval (PQI), left ventricular contractility (LVC), and left ventricular pressure (P(LV)) in seven pigs. Stimulation using the optimal bipolar configuration on the multi-contact cuff significantly affected RRI, PQI, LVC, and P(LV), whereas stimulation with the ring electrode only significantly affected RRI and PQI. The cardiovascular parameters that could be significantly influenced varied between the bipolar configurations. These novel findings may be relevant for optimizing electrode configurations for clinical cardiac applications of vagal nerve stimulation.

An indirect component in the evoked compound action potential of the vagal nerve.

The vagal nerve plays a vital role in the regulation of the cardiovascular system. It not only regulates the heart but also sends sensory information from the heart back to the brain. We hypothesize that the evoked vagal nerve compound action potential contains components that are indirect via the brain stem or coming via the neural network on the heart. In an experimental study of 15 pigs, we identified four components in the evoked compound action potentials. The fourth component was found to be an indirect component, which came from the periphery. The latency of the indirect component increased when heart rate and contractility were decreased by burst stimulation (P = 0.01; n = 7). When heart rate and contractility were increased by dobutamine administration, the latency of the indirect component decreased (P = 0.01; n = 9). This showed that the latency of the indirect component of the evoked compound action potentials may relate to the state of the cardiovascular system.

Electrode contact configuration and energy consumption in spinal cord stimulation.

OBJECTIVE: To test the hypothesis that in spinal cord stimulation, an increase in the number of cathodes increases the energy per pulse, contrary to an increase in the number of anodes, which decreases energy consumption per pulse. METHODS: Patients with an Itrel III (7425; Medtronic, Inc., Minneapolis, MN) implantable pulse generator and a Pisces-Quad (3487A; Medtronic, Inc.) implantable quadripolar lead were selected for this study. A set of 7 standard contact configurations was used for each patient. Resistor network models mimicking these configurations were constructed. The University of Twente's Spinal Cord Stimulation software was used to simulate the effect of these contact configurations on large spinal nerve fibers. To allow a comparison of the measured and modeled energy per pulse, all values were normalized. RESULTS: Both the empirical and the modeling results showed an increase in energy consumption with an increasing number of cathodes. Although the patient data with 1 and 2 cathodes did not differ significantly, energy consumption was significantly higher when 3 cathodes were used instead of 1 or 2 cathodes. The average energy consumption was significantly higher when bipolar stimulation was used instead of monopolar cathodal stimulation. An increasing number of anodes caused a decrease in energy consumption. CONCLUSION: When the paresthesia area can be covered with several configurations, it will be beneficial for the patient to program a configuration with 1 cathode and either no or multiple anodes.

Effect and safety of spinal cord stimulation for treatment of chronic pain caused by diabetic neuropathy.

AIM: Spinal cord stimulation (SCS) has been shown effective as a therapy for different chronic painful conditions, but the effectiveness of this treatment for pain as a result of peripheral diabetic neuropathy is not well established. The primary objectives of this study were to evaluate the effect and safety of SCS for treatment of pain and the effects on microcirculatory blood flow in the affected areas in patients with refractory peripheral diabetic neuropathy. METHOD: The study was designed as a prospective, open-label study. Data were collected during screening, at implant and at regular intervals, after initiation of therapy. Eleven diabetic patients with chronic pain in their lower limbs and no response to conventional treatment were studied. The SCS electrode was implanted in the thoracic epidural space. Neuropathic pain relief was assessed by Visual Analogue Scale (VAS) and microcirculatory skin perfusion was measured with Laser Doppler flowmetry. RESULTS: Nine subjects had significant pain relief with the percutaneous electrical stimulator. Average pain score for all nine patients was 77 at baseline and 34 at 6 months after implantation. At the end of the study, eight of nine patients continued to experience significant pain relief and have been able to significantly reduce their pain medication. For six of them, the stimulator was the sole treatment for their neuropathic pain. No significant changes in microcirculatory perfusion were recorded. CONCLUSION: Spinal cord stimulation offers an effective and safe therapy for chronic diabetic neuropathic pain.

A randomized controlled trial of an implantable 2-channel peroneal nerve stimulator on walking speed and activity in poststroke hemiplegia.

OBJECTIVE: To determine the effect of a new implantable 2-channel peroneal nerve stimulator on walking speed and daily activities, in comparison with the usual treatment in chronic stroke survivors with a drop foot. DESIGN: Randomized controlled trial. SETTING: All subjects were measured 5 times in the gait laboratory. PARTICIPANTS: Twenty-nine stroke survivors with chronic hemiplegia with drop foot who fulfill the predefined inclusion and exclusion criteria were included in the study. INTERVENTION: The intervention group received an implantable 2-channel peroneal nerve stimulator for correction of their drop foot. The control group continued using their conventional walking device, consisting of an ankle-foot orthosis, orthopedic shoes, or no device. MAIN OUTCOME MEASURES: Walking speed, assessed both by a six-minute walk test (6MWT) and by using a 10-m walkway, was selected as primary outcome measure and activity monitoring data, consisting of percentage time spent on stepping, standing, and sitting/lying were selected as secondary outcome measure. RESULTS: Functional electric stimulation (FES) resulted in a 23% improvement of walking speed measured with the 6MWT, whereas the improvement in the control group was only 3% (P=.010). Comfortable walking speed measured on a 10-m walkway was also significantly improved in favor of FES (P=.038). The percentage time spent on stepping deteriorated with 3% in the intervention and 0.8% in control group, which was not statistically significant between both groups (P=.13). CONCLUSIONS: The present study shows a clinically relevant effect of the implantable 2-channel peroneal nerve stimulator on walking speed in the sample of stroke survivors included in our study.

Two cases of autosomal recessive generalized dystonia in childhood: 5 year follow-up and bilateral globus pallidus stimulation results.

We report two brothers with an unknown form of early-onset familiar dystonia. Characteristic clinical features are (1) childhood-onset; (2) extrapyramidal motor symptoms; (3) dysarthria; and (4) mental retardation. Additional findings include loss of D(2)-receptors in both basal ganglia and hypoplasia of the cerebellar vermis with dilatation of the fourth ventricle and cisterna magna. There seems to be a progressive and non-progressive form of this clinical entity. Dystonic symptoms of the progressive form that occurred in one of the brothers were alleviated dramatically by bilateral internal globus pallidus (Gpi) stimulation, and the improvement has lasted now for 5 years.

Heart rate control via vagus nerve stimulation.

Objectives. There is ample and well-established evidence that direct electrical stimulation of the vagus nerve can change heart rate in animals and humans. Since tachyarrhythmias cannot always be controlled through medication, we sought, in this pilot study, to elucidate whether a clinical implantable lead system that is used in cervical vagus nerve stimulation therapy (VNS therapy) also can be used for control of heart rate, and tachycardia in particular. Materials and Methods. Experiments were carried out in three pigs (weight 21-26 kg) under general anesthesia. The right and left vagus nerves in the neck region were exposed by dissection, and bipolar, multiturn, helical, silicone leads were wrapped around the vagus nerves. Stimulation was applied by an external device with multivariable settings: frequency 10-100 Hz, pulse duration 100-700 µsec; delay 0-0.5 msec; current 0.5-14 mA. Measurements were performed under normal sinus rhythm (RR-interval 501 ± 30 msec) and during isoprenaline-induced tachycardia (RR-interval 284 ± 11 msec). Results. VNS, under optimal pacing conditions (100 Hz; 5 mA; 0.2 msec; 70 msec delay), in an electrocardiogram-triggered (ECG-triggered) pacing mode, increased RR-intervals by approximately 40%, irrespective of the duration of the RR-interval preceding VNS. The maximum effect on heart rate was established within approximately 5 sec after the onset of stimulation and was reversible and reproducible. No differences were found between stimulation of the right or left vagus nerve. Conclusion. VNS can be used effectively and rapidly to decrease heart rate, in acute settings, when connected to an external pacing system. Future devices that are fully implantable may be used for nonpharmacological treatment of illnesses in which tachycardia results in deterioration of cardiac function.

The sensitivity and selectivity of an implantable two-channel peroneal nerve stimulator system for restoration of dropped foot.

The objective of this study was to evaluate the stimulation responses on each channel of an implantable two-channel stimulator that stimulates the peroneal nerve branches innervating the muscles for dorsiflexion and eversion movements. Currently five Dutch patients and five English patients have been implanted with this system. Isometric ankle torque measurements were carried out in the patient with the longest follow-up period (1 y). A force sensor measured the three components of moment generated at the ankle joint. Stimulation intensity can be adjusted with great accuracy. Dorsiflexion moments are almost entirely determined by the setting of channel 1. Eversion moments are determined mainly by channel 2 and to a lesser extent by channel 1. Both channels determined abduction/adduction moments. We conclude that stimulation responses in both dorsiflexion and eversion direction can be set individually and with great accuracy and are reproducible over a prolonged period.

Laryngeal and vocal changes during vagus nerve stimulation in epileptic patients.

Left vagus nerve stimulation (VNS) by means of an implanted electrode has proven to reduce seizure frequency in epileptic patients with medically refractory seizures. This technique is now widely applied over the world. Voice changes appear to be one of the major side effects. The morphodynamic changes in the larynx and the acoustic impacts have been analyzed in detail in 7 implanted patients. Basic vagus stimulation is well tolerated. Extra stimulation induces an adductory spasm of either the ipsilateral vocal fold or the vestibular fold. The result, when the patient phonates, consists of a slight increase of F0 as well as a moderate increase of random period perturbation, but there is no evidence for the occurrence of "bifurcations." Further, as the glottic closure remains sufficient, there is no increase in turbulent noise. The lack of increase in turbulent noise and the lack of "bifurcations" appears to clearly differentiate a spasmodic contraction of the vocal cord from a unilateral vocal fold paralysis.