Combined Spinal Cord and Peripheral Nerve Field Stimulation for Persistent Post‐Herniorrhaphy Pain

Objectives: Chronic post‐hernia pain is a common complication after inguinal herniorrhaphies. Peripheral nerve field stimulation (PNFS) and spinal cord stimulation (SCS) are two new promising treatment modalities. Four patients with persistent neuropathic post‐hernia pain were recruited for this prospective study. Materials and Methods: Electrodes were inserted into the epidural space of the spinal canal and into the subcutaneous tissue in the inguinal region during a single surgical procedure. During a 14‐day trial, double‐blind stimulation was performed via an external stimulator: three days using the spinal electrode (SCS), three days using the inguinal electrode (PNFS), three days using both (SCS + PNFS), and five days off, with an alternating order from patient to patient. During the trial, pain intensity was assessed thrice daily by the visual analog scale. Additionally, pain intensity and quality of life (QOL) were assessed before and after surgical intervention by the Brief Pain Inventory, SF36 scale, and Pain Disability Index. Results: All patients had a marked pain reduction during the trial phase, and this reduction was more prominent when both electrodes were activated simultaneously (p < 0.001). At the late follow‐up, a significant pain reduction and improvement of QOL was observed in three patients. Conclusions: Both SCS and PNFS are effective in treating post‐hernia pain, but the magnitude of pain reduction was more prominent with concomitant stimulation. Combined PNFS and SCS should be considered for patients with a less than optimal response to either SCS or PNFS. More studies are necessary to address the cost‐effect issues of this new approach to treatment.     

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

IntroductionPersistent 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 MethodsThis 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.ResultsThere 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).ConclusionIn 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 RegistrationThe Clinicaltrials.gov registration number for the study is NCT01776749.     

Efficacy and Safety of Vagus Nerve Stimulation in Patients With Complex Partial Seizures

Summary: A clinical trial of chronic intermittent vagal stimulation in five patients suggests that the procedure may be safe and effective as adjunctive treatment of medically intractable seizures of partial onset. Patients tolerated well the implantation of the neurocybernetic prosthesis and the vagal stimulation without serious physiological or lifestyle changes. Stimulation of the vagus nerve either reduced the seizure frequency or decreased the duration or intensity of seizures. Adverse side effects were limited to a tingling sensation in the throat and hoarseness during stimulation. A major complication was mechanical interruption of the wire-electrode circuitry, with consequent cessation of stimulation. The small number of patients and the relatively short follow-up period make this a pilot study, but the results are promising.     

Continuous Vagus Nerve Stimulation Effects on the Gut‐Brain Axis in Swine

Objectives. This study was designed to assess vagus nerve stimulation effects on the food intake pattern in swine and determine the electrical stimulus direction. Material and Methods. Fifteen Large White pigs were randomly divided into three groups, groups A–C. All animals underwent implantation of a vagus nerve stimulator at the gastro‐esophogeal junction. In group A, the stimulation was switched off, whereas stimulation was switched on in groups B and C. Food intake and body weight were registered in groups A and B, but not in group C, which was used to measure direction of stimulation in the vagus and effect on heart rate and blood pressure. Variables measured in group C included the bispectral index, blood pressure, and heart rate. A Student's t‐test and one‐way analysis of variance were used to detect differences between groups. All animals were sacrificed to identify effects of implantation and stimulation on the vagus nerve. Results. With respect to food intake, there was no difference between groups A and B; however, body weight did register a continuous increase. During stimulation, in group C arterial pressures decreased significantly, whereas the heart rate and bispectral index increased. Conclusion. The stimulation protocol applied in this study was insufficient to cause changes in the feeding behavior of swine; however, it did increase central nervous system activity.     

The Effects of Temporary Spinal Cord Stimulation (or Spinal Nerve Root Stimulation) on the Management of Early Postherpetic Neuralgia from One to Six Months of Its Onset

Objective: We examined the efficacy of temporary spinal cord stimulation involving the insertion of only a needle and quadripolar lead into the epidural space and applied using an extracorporeal stimulation generator for a few weeks of early postherpetic neuralgia from one to six months of its onset. Materials and Methods: Temporary spinal cord stimulation was applied in 33 patients with postherpetic neuralgia and in whom epidural block was effective. Temporary spinal cord stimulation was applied over seven days, and analgesic effects was evaluated based on visual analog scale (VAS) values before and after one, three, and six months following treatment. An analgesic effect was defined as a decrease of over 50% in the VAS value compared with before treatment. Results: VAS values decreased significantly from 68.1 mm (standard deviation [SD]± 15.2) before treatment to 37.5 mm (SD ± 20.4) after one month, to 38.0 mm (SD ± 18.7) after three months, and to 35.0 mm (SD ± 21.3) after six months. In 21/33 (63.6%) cases, an analgesic effect, defined as a decrease in the VAS value of greater than 50%, was observed one month after treatment, in 20/33 (60.6%) cases such an effect was observed three months after treatment, and in 21/33 (63.6%) cases the effect was still observed six months after treatment. Conclusions: Temporary spinal cord stimulation is an effective analgesic method for early postherpetic neuralgia from one to six months of its onset.     

Impact of Cardiac-Based Vagus Nerve Stimulation Closed-Loop Stimulation on the Seizure Outcome of Patients With Generalized Epilepsy: A Prospective,Individual-Control Study

ObjectivesWe designed a prospective, individual-controlled study to evaluate the effect of cardiac-based VNS (cbVNS) in a cohort of patients with generalized epilepsy (GE).Materials and MethodsTwenty patients were included. They were followed up for six months under regular VNS (rVNS) and subsequently for six months during cbVNS. Stimulation parameters were 500 μsec, 30 Hz, and up to 2.5 mA. Seizure frequency was documented after two, four, and six months during the rVNS and cbVNS phases. Patients with at least 50% seizure frequency reduction were considered responders. The total and relative amount of stimulation cycles generated by both rVNS and cbVNS activation were documented. Findings during rVNS were compared to baseline and cbVNS data were compared to those during rVNS.ResultsThere was a significant decrease in mean seizure frequency (61% [95% CI, 48-74]; p < 0.001) during the rVNS phase compared to baseline. There was no additional significant (16% [95% CI, 4-35]; p = 0.097) mean seizure frequency reduction during cbVNS compared to the rVNS phase. Fifteen patients (75%) were considered responders after rVNS. Four patients (20%) were considered responders after six months of cbVNS. During the cbVNS phase, the mean total number of cycles/day was 346, 354, and 333 for months two, four, and six, respectively; the cycles generated by rVNS were 142, 138, and 146 for months two, four, and six, respectively; and cycles generated by cbVNS were 204, 215, and 186 for months two, four, and six, respectively. There was no relationship between the mean total number of cycles (−6[95% CI, −85 to 72]; p = 0.431), the mean number of auto-stimulation cycles (27[95% CI,−112 to 166]; p = 0.139), the mean number of regular cycles (−33[95% CI,−123 to 57]; p = 0.122), or the mean percentage of auto-stimulation cycles (13[95% CI,19- 45]; p = 0.109) and outcome during the cbVNS phase. Eight patients showed some decrease in seizure frequency during cbVNS.ConclusionsrVNS was effective in reducing seizure frequency in patients with generalized epilepsy, but activation of the cbVNS feature did not add significantly to rVNS efficacy. On the other hand, although not statistically significant, 40% of the patients showed some reduction in seizure frequency, which might prove useful at an individual level.     

Transcutaneous Vagus Nerve Stimulation in Humans Induces Pupil Dilation and Attenuates Alpha Oscillations

Vagus nerve stimulation (VNS) is widely used to treat drug-resistant epilepsy and depression. While the precise mechanisms mediating its long-term therapeutic effects are not fully resolved, they likely involve locus coeruleus (LC) stimulation via the nucleus of the solitary tract, which receives afferent vagal inputs. In rats, VNS elevates LC firing and forebrain noradrenaline levels, whereas LC lesions suppress VNS therapeutic efficacy. Noninvasive transcutaneous VNS (tVNS) uses electrical stimulation that targets the auricular branch of the vagus nerve at the cymba conchae of the ear. However, the extent to which tVNS mimics VNS remains unclear. Here, we investigated the short-term effects of tVNS in healthy human male volunteers (n = 24), using high-density EEG and pupillometry during visual fixation at rest. We compared short (3.4 s) trials of tVNS to sham electrical stimulation at the earlobe (far from the vagus nerve branch) to control for somatosensory stimulation. Although tVNS and sham stimulation did not differ in subjective intensity ratings, tVNS led to robust pupil dilation (peaking 4–5 s after trial onset) that was significantly higher than following sham stimulation. We further quantified, using parallel factor analysis, how tVNS modulates idle occipital alpha (8–13Hz) activity identified in each participant. We found greater attenuation of alpha oscillations by tVNS than by sham stimulation. This demonstrates that tVNS reliably induces pupillary and EEG markers of arousal beyond the effects of somatosensory stimulation, thus supporting the hypothesis that tVNS elevates noradrenaline and other arousal-promoting neuromodulatory signaling, and mimics invasive VNS.SIGNIFICANCE STATEMENT Current noninvasive brain stimulation techniques are mostly confined to modulating cortical activity, as is typical with transcranial magnetic or transcranial direct/alternating current electrical stimulation. Transcutaneous vagus nerve stimulation (tVNS) has been proposed to stimulate subcortical arousal-promoting nuclei, though previous studies yielded inconsistent results. Here we show that short (3.4 s) tVNS pulses in naive healthy male volunteers induced transient pupil dilation and attenuation of occipital alpha oscillations. These markers of brain arousal are in line with the established effects of invasive VNS on locus coeruleus–noradrenaline signaling, and support that tVNS mimics VNS. Therefore, tVNS can be used as a tool for studying how endogenous subcortical neuromodulatory signaling affects human cognition, including perception, attention, memory, and decision-making; and also for developing novel clinical applications.     

Effect of Temporary Spinal Cord Stimulation on Postherpetic Neuralgia in the Thoracic Nerve Area

Objectives. The pain associated with herpes zoster can be classified as acute phase, persistent phase, or chronic phase, but if it is prolonged, it becomes resistant to treatment. It is clinically important to prevent transition to postherpetic neuralgia after the onset of herpes zoster, and the outcome depends on whether continuous and potent pain management can be achieved between the acute and persistent phases. We evaluated the effect of pain management leading to quick termination of pain using temporary spinal cord stimulation (SCS) which does not require implantation of a device. Materials and Methods. We performed continuous epidural blocks (CEB) on 52 patients with severe persistent pain of postherpetic neuralgia in the thoracic nerve area, and also inserted spinal stimulation leads in 14 who showed no improvement in the severe pain with concomitant pharmacotherapy. We expected to see the termination of pain with adequate analgesic effects mainly with SCS, and secondarily with the epidural analgesia as rescue therapy. Results. Severe pain accompanied by sensory dysfunction remained in 14 cases. By introducing SCS to the CEB, the visual analog scale baseline was rapidly reduced. Less epidural analgesia was required and the adverse reactions of lowered blood pressure in three cases and urinary retention in seven cases disappeared soon. The self‐rated satisfaction was higher with SCS than with CEB in all 14 cases, because it is highly controllable and has minimal activities of daily living–lowering effects. Conclusion. Temporary SCS, which does not require implantation of a device, may have a potent analgesic effect on severe pain in patients in the persistent phase after herpes zoster, and prevent transition to postherpetic neuralgia.     

Prospective,Two-part Study of the Interaction Between Spinal Cord Stimulation and Peripheral Nerve Field Stimulation in Patients with Low Back Pain: Development of a New Spinal-Peripheral Neurostimulation Method

Objective: The goal of the study was to assess the efficacy of interaction between spinal cord stimulation (SCS) and peripheral nerve field stimulation (PNFS) and to evaluate a new spinal‐peripheral neuromodulation method for low back pain. Materials and Methods: The prospective two‐part study included patients with low back pain due to failed back surgery syndrome and/or spinal stenosis. In the first part 20 patients were implanted with SCS and PNFS. They selected the best program out of three: SCS alone, PNFS alone, or both together. In the second part another 20 patients with the same implanted leads were selecting between three programs: SCS and PNFS separately, SCS as anode and PNFS as cathode, or in reverse. Results: In the first part 79% of the patients selected simultaneous use of SCS and PNFS. The overall success of the trials was 85%. In the second part communication between SCS and PNFS provided wider coverage of axial pain. The overall success of the trials was 90%. Conclusion: Simultaneous use of SCS and PNFS increase efficacy of both methods for axial back pain. The new SPN method showed great potential in providing coverage for back pain.