Amplitude synchronization of spontaneous activity of medial and lateral temporal gyri reveals altered thalamic connectivity in patients with temporal lobe epilepsy.

In this study, we examined whether amplitude synchronization of medial (MTL) and lateral (LTL) temporal lobes can detect unique alterations in patients with MTL epilepsy (mTLE) with mesial temporal sclerosis (MTS). This was a retrospective study of preoperative resting-state fMRI (rsfMRI) data from 31 patients with mTLE with MTS (age 23-69) and 16 controls (age 21-35). fMRI data were preprocessed based on a multistep preprocessing pipeline and registered to a standard space. Using each subject's T1-weighted scan, the MTL and LTL were automatically segmented, manually revised and then fit to a standard space using a symmetric normalization registration algorithm. Dual regression analysis was applied on preprocessed rsfMRI data to detect amplitude synchronization of medial and lateral temporal segments with the rest of the brain. We calculated the overlapped volume ratio of synchronized voxels within specific target regions including the thalamus (total and bilateral). A general linear model was used with Bonferroni correction for covariates of epilepsy duration and age of patient at scan to statistically compare synchronization in patients with mTLE with MTS and controls, as well as with respect to whether patients remained seizure-free (SF) or not (NSF) after receiving epilepsy surgery. We found increased ipsilateral positive connectivity between the LTLs and the thalamus and contralateral negative connectivity between the MTLs and the thalamus in patients with mTLE with MTS compared to controls. We also found increased asymmetry of functional connectivity between temporal lobe subregions and the thalamus in patients with mTLE with MTS, with increased positive connectivity between the LTL and the lesional-side thalamus as well as increased negative connectivity between the MTL and the nonlesional-side thalamus. This asymmetry was also seen in NSF patients but was not seen in SF patients and controls. Amplitude synchronization was an effective method to detect functional connectivity alterations in patients with mTLE with MTS. Patients with mTLE with MTS overall showed increased temporal-thalamic connectivity. There was increased functional involvement of the thalamus in MTS, underscoring its role in seizure spread. Increased functional thalamic asymmetry patterns in NSF patients may have a potential role in prognosticating patient response to surgery. Elucidating regions with altered functional connectivity to temporal regions can improve understanding of the involvement of different regions in the disease to potentially target for intervention or use for prognosis for surgery. Future studies are needed to examine the effectiveness of using patient-specific abnormalities in patterns to predict surgical outcome.

Costs Associated with Laser Interstitial Thermal Therapy Are Lower Than Anterior Temporal Lobectomy for Treatment of Temporal Lobe Epilepsy.

BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimally invasive alternative to anterior temporal lobectomy (ATL) for treatment of temporal lobe epilepsy. It has gained popularity as familiarity with technique increases and outcomes are better characterized. There has been no direct cost comparison between the 2 techniques in literature to date. The current study directly compares hospital costs associated with LITT with those of ATL patients and analyzes the factors potentially responsible for those costs. METHODS: Patients who underwent ATL (27) and LITT (15) were retrospectively reviewed for total hospital costs along with demographic, surgical, and postoperative factors potentially affecting cost. T-tests were used to compare costs and independent linear regressions, and hierarchical regressions were used to examine predictors of cost for each procedure. RESULTS: Mean hospital costs of admission for single-trajectory LITT ($104,929.88) were significantly less than for ATL ($134,980.04) (P = 0.001). In addition, length of stay, anesthesia costs, operative room costs, and postoperative hospitalization costs were all significantly lower in LITT. CONCLUSIONS: Given the minimally invasive nature of LITT, it is associated with shorter length of stay and lower hospital costs than ATL in the first head-to-head comparison of procedural costs in literature to date. Long-term efficacy as it relates to these costs associated with LITT and ATL should be further investigated to better characterize the utility of LITT in temporal lobe epilepsy patients.

First-in-human implantation of a mid-field powered neurostimulator at the sacral nerve: Results from an acute study.

INTRODUCTION: Commercially approved implantable systems for sacral neuromodulation require the implantation of a multipolar lead subcutaneously connected to an implantable pulse generator (IPG). Eliminating the need for an IPG would eliminate the need for tunneling of the lead, reduce procedure time, infection risk, and the need for IPG replacement. The objective was to demonstrate the feasibility of implanting the AHLeveeS System in the S3 Foramen to stimulate the S3 sacral nerve. MATERIALS AND METHODS: A first-in-human, prospective, single center, nonrandomized, acute feasibility clinical investigation at the Maastricht University Medical Center+. Patients with refractory overactive bladder underwent acute implantation of the AHLeveeS neurostimulator before the InterStim procedure. Outcome measurements included motor responses, procedural time and a scoring of the difficulty of the implant and explant procedure. Retrospectively, qualitative responses to the stimulation protocol were assessed by video motion analyses. Only descriptive statistics were used. RESULTS: During the stimulation a motor response to stimulation was seen in four of the five subjects. In all implantations the AHLeveeS was correctly placed. The median time for complete procedure was 24 minutes. The implant and explant procedures were successfully performed and no device or procedure related adverse events occurred. CONCLUSIONS: The results from this acute first-in-human study demonstrate the feasibility of implantation and acute stimulation of the sacral nerve with this mid-field powered system. Future clinical studies will focus on safety and efficacy of a chronically implanted device.

Neuronal phase consistency tracks dynamic changes in acoustic spectral regularity.

The brain parses the auditory environment into distinct sounds by identifying those acoustic features in the environment that have common relationships (e.g., spectral regularities) with one another and then grouping together the neuronal representations of these features. Although there is a large literature that tests how the brain tracks spectral regularities that are predictable, it is not known how the auditory system tracks spectral regularities that are not predictable and that change dynamically over time. Furthermore, the contribution of brain regions downstream of the auditory cortex to the coding of spectral regularity is unknown. Here, we addressed these two issues by recording electrocorticographic activity, while human patients listened to tone-burst sequences with dynamically varying spectral regularities, and identified potential neuronal mechanisms of the analysis of spectral regularities throughout the brain. We found that the degree of oscillatory stimulus phase consistency (PC) in multiple neuronal-frequency bands tracked spectral regularity. In particular, PC in the delta-frequency band seemed to be the best indicator of spectral regularity. We also found that these regularity representations existed in multiple regions throughout cortex. This widespread reliable modulation in PC - both in neuronal-frequency space and in cortical space - suggests that phase-based modulations may be a general mechanism for tracking regularity in the auditory system specifically and other sensory systems more generally. Our findings also support a general role for the delta-frequency band in processing the regularity of auditory stimuli.

Automated trajectory planning for laser interstitial thermal therapy in mesial temporal lobe epilepsy.

OBJECTIVE: Surgical resection of the mesial temporal structures brings seizure remission in 65% of individuals with drug-resistant mesial temporal lobe epilepsy (MTLE). Laser interstitial thermal therapy (LiTT) is a novel therapy that may provide a minimally invasive means of ablating the mesial temporal structures with similar outcomes, while minimizing damage to the neocortex. Systematic trajectory planning helps ensure safety and optimal seizure freedom through adequate ablation of the amygdalohippocampal complex (AHC). Previous studies have highlighted the relationship between the residual unablated mesial hippocampal head and failure to achieve seizure freedom. We aim to implement computer-assisted planning (CAP) to improve the ablation volume and safety of LiTT trajectories. METHODS: Twenty-five patients who had previously undergone LiTT for MTLE were studied retrospectively. The EpiNav platform was used to automatically generate an optimal ablation trajectory, which was compared with the previous manually planned and implemented trajectory. Expected ablation volumes and safety profiles of each trajectory were modeled. The implemented laser trajectory and achieved ablation of mesial temporal lobe structures were quantified and correlated with seizure outcome. RESULTS: CAP automatically generated feasible trajectories with reduced overall risk metrics (P < .001) and intracerebral length (P = .007). There was a significant correlation between the actual and retrospective CAP-anticipated ablation volumes, supporting a 15 mm diameter ablation zone model (P < .001). CAP trajectories would have provided significantly greater ablation of the amygdala (P = .0004) and AHC (P = .008), resulting in less residual unablated mesial hippocampal head (P = .001), and reduced ablation of the parahippocampal gyrus (P = .02). SIGNIFICANCE: Compared to manually planned trajectories CAP provides a better safety profile, with potentially improved seizure-free outcome and reduced neuropsychological deficits, following LiTT for MTLE.

Presurgical thalamic "hubness" predicts surgical outcome in temporal lobe epilepsy.

OBJECTIVE: To characterize the presurgical brain functional architecture presented in patients with temporal lobe epilepsy (TLE) using graph theoretical measures of resting-state fMRI data and to test its association with surgical outcome. METHODS: Fifty-six unilateral patients with TLE, who subsequently underwent anterior temporal lobectomy and were classified as obtaining a seizure-free (Engel class I, n = 35) vs not seizure-free (Engel classes II-IV, n = 21) outcome at 1 year after surgery, and 28 matched healthy controls were enrolled. On the basis of their presurgical resting-state functional connectivity, network properties, including nodal hubness (importance of a node to the network; degree, betweenness, and eigenvector centralities) and integration (global efficiency), were estimated and compared across our experimental groups. Cross-validations with support vector machine (SVM) were used to examine whether selective nodal hubness exceeded standard clinical characteristics in outcome prediction. RESULTS: Compared to the seizure-free patients and healthy controls, the not seizure-free patients displayed a specific increase in nodal hubness (degree and eigenvector centralities) involving both the ipsilateral and contralateral thalami, contributed by an increase in the number of connections to regions distributed mostly in the contralateral hemisphere. Simulating removal of thalamus reduced network integration more dramatically in not seizure-free patients. Lastly, SVM models built on these thalamic hubness measures produced 76% prediction accuracy, while models built with standard clinical variables yielded only 58% accuracy (both were cross-validated). CONCLUSIONS: A thalamic network associated with seizure recurrence may already be established presurgically. Thalamic hubness can serve as a potential biomarker of surgical outcome, outperforming the clinical characteristics commonly used in epilepsy surgery centers.

JOURNAL CLUB: Longitudinal Qualitative Characterization of MRI Features After Laser Interstitial Thermal Therapy in Drug-Resistant Epilepsy.

OBJECTIVE: Laser interstitial thermal therapy (LITT), a method for ablating brain tissue under real-time MR thermometry, has been used more frequently in recent years to treat nonmalignant lesions. The purpose of this study is to longitudinally characterize MRI features after LITT in patients with drug-resistant epilepsy, primarily in the setting of mesial temporal sclerosis. MATERIALS AND METHODS: MR images from 23 consecutive patients who underwent LITT were retrospectively reviewed. All patients had images obtained immediately after the ablation. Multiple patients had follow-up imaging at various time points after treatment, from postoperative days 7 through 1539. A total of 54 MRI studies were reviewed. RESULTS: Immediately after LITT, MR images showed a ring-enhancing lesion at the ablation site with minimal surrounding edema. Seven images showed increased enhancement of the ipsilateral choroid plexus. Images in the subacute phase showed a mild increase in edema with similar enhancement. Images in the transitional phase showed a decrease in edema with variable enhancement. Images in the chronic phase showed minimal gliosis with or without cavity formation or cavity formation alone, with either decreased or no enhancement. CONCLUSION: This report describes the time course of the imaging findings after LITT for drug-resistant epilepsy. The typical stages include rim-enhancing lesion with minimal edema, followed by an increase in edema, to eventual gliosis and nonenhancing cavity formation. Radiologists need to be familiar with the postablation findings to minimize misdiagnosis and prevent unnecessary workup.

Long-Term Pain Reduction Does Not Imply Improved Functional Outcome in Patients Treated With Combined Supraorbital and Occipital Nerve Stimulation for Chronic Migraine.

BACKGROUND: Dual supraorbital and occipital nerve stimulation (SONS and ONS) have shown promising efficacy in treating primary headaches. However, its functional outcome is not well studied. OBJECTIVE: To present functional outcome studies of combined SONS and ONS for chronic migraine using verified metrics. METHOD: Consecutive patients with both SONS and ONS assessed with Migraine Disability Assessment (MIDAS) and Beck Depression Index (BDI) both preoperatively and postoperatively were studied. Selected predictor variables included patients with ≥50% improvement of pain, disability status, number of years from diagnosis to implantation, and narcotic use. Functional outcome variables included net improvement of ranked MIDAS and BDI scores. Multivariate analysis of variance was performed to assess the correlation between the outcome and predictor variables. RESULTS: Sixteen patients (12 female; average age 52 years old) were studied. Follow-up ranged from 5 to 80 months (average 44.5; σ = 21.4 months). At most recent follow-up, eight patients had a positive response (≥50% improvement in headache), which was the only predictor of functional outcome (total MIDAS, MIDAS-B, and BDI) (p = 0.021). Of note, improvement in functional outcome was only significant during the perioperative 3-6 months period and not throughout long-term follow-up. Among the predictor variables, a strong inverse correlation was found between disability status and positive response to stimulation (r = -0.582). CONCLUSION: There is a paucity of studies in quality of life, productivity, and psychosocial aspects with peripheral nerve stimulation therapy for headache. Patients with a positive response to SONS and ONS also reported overall improvement in their functional status as reflected by MIDAS and BDI in the perioperative period. Unfortunately, this effect waned over the long-term follow-up.

Occipital Nerve Stimulation for the Treatment of Patients With Medically Refractory Occipital Neuralgia: Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline.

BACKGROUND: Occipital neuralgia (ON) is a disorder characterized by sharp, electrical, paroxysmal pain, originating from the occiput and extending along the posterior scalp, in the distribution of the greater, lesser, and/or third occipital nerve. Occipital nerve stimulation (ONS) constitutes a promising therapy for medically refractory ON because it is reversible with minimal side effects and has shown continued efficacy with long-term follow-up. OBJECTIVE: To conduct a systematic literature review and provide treatment recommendations for the use of ONS for the treatment of patients with medically refractory ON. METHODS: A systematic literature search was conducted using the PubMed database and the Cochrane Library to locate articles published between 1966 and April 2014 using MeSH headings and keywords relevant to ONS as a means to treat ON. A second literature search was conducted using the PubMed database and the Cochrane Library to locate articles published between 1966 and June 2014 using MeSH headings and keywords relevant to interventions that predict response to ONS in ON. The strength of evidence of each article that underwent full text review and the resulting strength of recommendation were graded according to the guidelines development methodology of the American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Guidelines Committee. RESULTS: Nine studies met the criteria for inclusion in this guideline. All articles provided Class III Level evidence. CONCLUSION: Based on the data derived from this systematic literature review, the following Level III recommendation can be made: the use of ONS is a treatment option for patients with medically refractory ON.

Reduced thalamocortical functional connectivity in temporal lobe epilepsy.

OBJECTIVE: In temporal lobe epilepsy (TLE), the thalamus is well known for its role in the propagation and spread of epileptiform activity. However, the integrity of thalamocortical functional connectivity (FC) in TLE and its relation to specific seizure patterns have not yet been determined. We address these issues with resting-state functional magnetic resonance imaging (fMRI). METHODS: Resting-state fMRI was performed on two groups of unilateral TLE patients: those with focal seizures only (16 left TLE, 16 right TLE) and those with additional generalized seizures (16 left TLE, 10 right TLE), and 16 matched controls. A thalamic parcellation based on FC between five nonoverlapping cortical seeds (prefrontal, motor, somatosensory, parietal-occipital, and temporal) and the ipsilateral thalamus was carried out to parcel each thalamus into five corresponding segments. FCs between each segment and its ipsilateral cortical seed were extracted and compared across groups using analyses of variance (ANOVAs). RESULTS: Compared to healthy controls, patients with TLE displayed decreased thalamocortical FC in multiple posterior and ventromedial thalamic segments of both the ictal and nonictal hemispheres. Our parcellation analysis revealed that these thalamic regions were functionally connected to the parietal/occipital and temporal lobes. In patients with TLE with focal seizures these regional thalamocortical FC decreases were limited to the ictal hemisphere. In contrast, TLE patients with both focal and generalized epileptiform activity displayed FC decreases in both the ictal and nonictal thalamus involving the dorsolateral pulvinar, a region preferentially connected to the parietal and occipital lobes. SIGNIFICANCE: Our data provide the first evidence of regional specific thalamocortical FC decreases in patients with unilateral TLE. Furthermore, our results demonstrate that patients with different seizure types present different thalamoparietal/occipital FC decrease patterns. While patients with focal seizures present thalamocortical FC decreases in the ictal hemisphere only, patients with additional generalized seizure activity also show thalamocortical FC decreases involving the thalamus in the nonictal hemisphere.

Analysis of adverse events in the management of chronic migraine by peripheral nerve stimulation.

OBJECTIVE: In this study, we analyze device- and procedure-related adverse events (AEs) from a recent prospective, multicenter, double-blinded controlled study that utilized peripheral nerve stimulation (PNS) of occipital nerves for management of chronic migraine. METHODS: PNS device characteristics (lead length and spacing), surgical techniques including lead orientation (parallel or perpendicular to the nerve), and implantable pulse generator (IPG) placement (upper buttock, abdomen, infraclavicular, or lower axilla) in 157 patients were analyzed to identify any relationship with the AE incidence rate. Number of prior PNS implants performed (NPPIP) by the implanter and its relationship with different AE categories (hardware-related, biological, and stimulation-related events) and frequently observed device/procedure-related AEs (lead migration/fracture/breakage, persistent pain at the lead/IPG location, unintended/undesirable changes in stimulation, infection) were also evaluated. Three-way ANOVA tests were utilized to evaluate the dependence of AE occurrence on the variables described above. RESULTS: IPG pocket locations closer to the lead (e.g. infraclavicular region) were associated with a lower AE incidence rate (p < 0.05). Higher NPPIP was related to lower stimulation- and hardware-related AEs (p < 0.05), frequently observed AEs like lead migration, pain, and infection (p < 0.05), and procedure-related additional surgeries (p < 0.05). CONCLUSION: Implantation of the IPG closer to the lead location was associated with reduced AEs. PNS is a relatively new procedure, and the skill and precision in performing these procedures improves with experience. Our results demonstrate that as the implanter gains more experience with these procedures, a significant reduction in device- and procedure-related AEs may be expected.

Safety and efficacy of peripheral nerve stimulation of the occipital nerves for the management of chronic migraine: long-term results from a randomized, multicenter, double-blinded, controlled study.

BACKGROUND: Recent studies evaluated short-term efficacy and safety of peripheral nerve stimulation (PNS) of the occipital nerves for managing chronic migraine. We present 52-week safety and efficacy results from an open-label extension of a randomized, sham-controlled trial. METHODS: In this institutional review board-approved, randomized, multicenter, double-blinded study, patients were implanted with a neurostimulation system, randomized to an active or control group for 12 weeks, and received open-label treatment for an additional 40 weeks. Outcomes collected included number of headache days, pain intensity, migraine disability assessment (MIDAS), Zung Pain and Distress (PAD), direct patient reports of headache pain relief, quality of life, satisfaction and adverse events. Statistical tests assessed change from baseline to 52 weeks using paired t-tests. Intent-to-treat (ITT) analyses of all patients (N = 157) and analyses of only patients who met criteria for intractable chronic migraine (ICM; N = 125) were performed. RESULTS: Headache days were significantly reduced by 6.7 (±8.4) days in the ITT population (p < 0.001) and by 7.7 (±8.7) days in the ICM population (p < 0.001). The percentages of patients who achieved a 30% and 50% reduction in headache days and/or pain intensity were 59.5% and 47.8%, respectively. MIDAS and Zung PAD scores were significantly reduced for both populations. Excellent or good headache relief was reported by 65.4% of the ITT population and 67.9% of the ICM population. More than half the patients in both cohorts were satisfied with the headache relief provided by the device. A total of 183 device/procedure-related adverse events occurred during the study, of which 18 (8.6%) required hospitalization and 85 (40.7%) required surgical intervention; 70% of patients experienced an adverse event. CONCLUSION: Our results support the 12-month efficacy of PNS of the occipital nerves for headache pain and disability associated with chronic migraine. More emphasis on adverse event mitigation is needed in future research. TRIAL REGISTRATION: Clinical trials.gov (NCT00615342).

Dual occipital and supraorbital nerve stimulation for chronic migraine: a single-center experience, review of literature, and surgical considerations.

Occipital nerve stimulation (ONS) has been studied in a few clinical trials for the treatment of chronic migraine (CM) with failure to prove sufficient efficacy. To date, peripheral nerve stimulation for the treatment of primary headache is limited to off-label use only. The authors report their institutional experience in CM therapy with combined ONS and supraorbital nerve stimulation (SONS). Fourteen patients treated with dual ONS and SONS for CM were studied with follow-up ranging from 3 to 60 months. Seventy-one percent achieved successful stimulation as defined by a 50% or greater decrease in pain severity. The mean reduction in headache-related visual analog scale (VAS) score was 3.92 ± 2.4. Half of the patients also had resolution of migraine-associated neurological symptoms and returned to normal functional capacity. The main adverse events included lead migration (42.8%), supraorbital lead allodynia (21.4%), and infection (14.2%) with a resulting high reoperation rate (35.7%). The authors' stimulation efficacy was superior to the combined 33% positive response rates (≥ 50% pain reduction) in the published studies of ONS for CM. This is likely due to the fact that topographical paresthesia induced by combined ONS and SONS covers the area of migraine pain better than ONS alone. The authors also discuss effective surgical techniques to prevent patient morbidity.

Long-term measurement of impedance in chronically implanted depth and subdural electrodes during responsive neurostimulation in humans.

Long-term stability of the electrode-tissue interface may be required to maintain optimal neural recording with subdural and deep brain implants and to permit appropriate delivery of neuromodulation therapy. Although short-term changes in impedance at the electrode-tissue interface are known to occur, long-term changes in impedance have not previously been examined in detail in humans. To provide further information about short- and long-term impedance changes in chronically implanted electrodes, a dataset from 191 persons with medically intractable epilepsy participating in a trial of an investigational responsive neurostimulation device (the RNS(®) System, NeuroPace, Inc.) was reviewed. Monopolar impedance measurements were available for 391 depth and subdural leads containing a total of 1564 electrodes; measurements were available for median 802 days post-implant (range 28-1634). Although there were statistically significant short-term impedance changes, long-term impedance was stable after one year. Impedances for depth electrodes transiently increased during the third week after lead implantation and impedances for subdural electrodes increased over 12 weeks post-implant, then were stable over the subsequent long-term follow-up. Both depth and subdural electrode impedances demonstrated long-term stability, suggesting that the quality of long-term electrographic recordings (the data used to control responsive brain stimulation) can be maintained over time.

The functional anatomy of non-verbal (pitch memory) function in left and right anterior temporal lobectomy patients.

An fMRI pitch memory task was administered to left and right anterior temporal lobectomy (ATL) patients. The goal was to verify the neuroanatomical correlates of non-verbal memory, and to determine if pitch memory tasks can identify cognitive risk prior to ATL. The data showed that the bilateral posterior superior temporal lobes implement pitch memory in both ATL patients and NCs (normal controls), indicating that the task can be accomplished with either anterior temporal lobe resected. NCs activate the posterior temporal lobes more strongly than ATL patients during highly accurate performance. In contrast, both ATL groups activate the anterior cingulate in association with accuracy. While our data clarifies the functional neuroanatomy of pitch memory, it also indicates that such tasks do not serve well to lateralize and functionally map potentially "at risk" non-verbal memory skills prior to ATL.

Neurostimulation for the treatment of epilepsy: a review of current surgical interventions.

OBJECTIVES: Epilepsy continues to provide challenges to clinicians, as a significant proportion of patients continue to suffer from seizures despite medical and surgical treatments. Neurostimulation has emerged as a new treatment modality that has the potential to improve quality of life and occasionally be curative for patients with medically refractory epilepsy who are not surgical candidates. In order to continue to advance the frontier of this field, it is imperative to have a firm grasp of the current body of knowledge. METHODS: We performed a thorough review of the current literature regarding the three main modalities of vagus nerve stimulation, deep brain stimulation, and closed-loop stimulation (responsive neurostimulator [RNS]) for the treatment of refractory epilepsy. For each of these forms of treatment, we discuss the current understanding of the underlying mechanism of action, patient selection, outcomes to date, and associated side effects or adverse reactions. We also provide an overview of related ongoing clinical trials. RESULTS: A total of 189 sources from 1938 to 2012 pertaining to neuromodulation for the treatment of epilepsy were reviewed. Sources included review articles, clinical trials, case reports, conference proceedings, animal studies, and government data bases. CONCLUSIONS: This review shows us how neurostimulation provides us with yet another tool with which to treat the complex disease of medically refractory epilepsy.

Impedance variations over time for a closed-loop neurostimulation device: early experience with chronically implanted electrodes.

OBJECTIVE: Responsive neurostimulation (RNS®) is an investigational treatment modality for intractable focal epilepsy. We analyzed impedance values over time to gain a better understanding of RNS device stability, potential differences between depth and strip electrodes, and general implications of long-term electrode implantation. MATERIALS AND METHODS: Impedance measurements were retrospectively reviewed from seven patients over a 3-year period. Statistical analysis was performed to investigate trends in impedance values over time and to determine if any differences existed between the means and variances of impedance values for the two different electrodes. RESULTS: Intraparenchymal depth electrodes demonstrated lower mean impedances and had less variation over time when compared to subdural strip electrodes. There was no significant change in mean impedance over time for depth electrodes, while that of subdural electrodes increased over time to peak at 16-20 months and returned to baseline by 2 years. CONCLUSION: The RNS device provides unique long-term data for both depth and subdural electrodes in human subjects. Although changes in impedance were observed with respect to time after implantation and electrode type, these variations were of a clinically insignificant magnitude. As a constant-current system, the device is ultimately able to administer stable therapeutic doses in the setting such minor variability. While further animal research and post mortem investigations in human subjects are necessary to broaden our understanding of the mechanisms occurring at the electrode-neural interface and the biocompatibility of chronically implanted electrodes, the relative stability of impedances seen in this cohort of chronic implants brings promise to future implementations of chronic intracranial neural implants.

Safety and efficacy of peripheral nerve stimulation of the occipital nerves for the management of chronic migraine: results from a randomized, multicenter, double-blinded, controlled study.

BACKGROUND: Chronic migraine (CM) is a debilitating neurological disorder with few treatment options. Peripheral nerve stimulation (PNS) of the occipital nerves is a potentially promising therapy for CM patients. METHODS: In this randomized, controlled multicenter study, patients diagnosed with CM were implanted with a neurostimulation device near the occipital nerves and randomized 2:1 to active (n = 105) or sham (n = 52) stimulation. The primary endpoint was a difference in the percentage of responders (defined as patients that achieved a ≥50% reduction in mean daily visual analog scale scores) in each group at 12 weeks. RESULTS: There was not a significant difference in the percentage of responders in the Active compared with the Control group (95% lower confidence bound (LCB) of -0.06; p = 0.55). However, there was a significant difference in the percentage of patients that achieved a 30% reduction (p = 0.01). Importantly, compared with sham-treated patients, there were also significant differences in reduction of number of headache days (Active Group = 6.1, baseline = 22.4; Control Group = 3.0, baseline = 20.1; p = 0.008), migraine-related disability (p = 0.001) and direct reports of pain relief (p = 0.001). The most common adverse event was persistent implant site pain. CONCLUSION: Although this study failed to meet its primary endpoint, this is the first large-scale study of PNS of the occipital nerves in CM patients that showed significant reductions in pain, headache days, and migraine-related disability. Additional controlled studies using endpoints that have recently been identified and accepted as clinically meaningful are warranted in this highly disabled patient population with a large unmet medical need. TRIAL REGISTRATION: Clinical trials.gov (NCT00615342).

Spinal cord injury induced by a cervical spinal cord stimulator.

OBJECTIVE: The use of cervical spinal cord stimulators for the treatment of refractory neck and upper extremity pain is widely accepted and growing in use as a treatment modality. This case highlights a previously unreported potential complication of spinal cord stimulators. METHODS: Analysis of a patient with a cervical spinal cord stimulator presenting with a spinal cord injury. Patient was followed from presentation in the emergency room until 1-year follow-up in the office. RESULTS: The patient in this case presented after a fall and sustained a cervical spinal cord injury induced by the electrodes of her spinal cord stimulator working as a space occupying mass. CONCLUSION: As more patients are undergoing implantation of spinal cord stimulators we must be aware of the long-term risks that can be encountered.

Awake vs. asleep placement of spinal cord stimulators: a cohort analysis of complications associated with placement.

INTRODUCTION: Patients will typically undergo awake surgery for permanent implantation of spinal cord stimulation (SCS) in an attempt to optimize electrode placement using patient feedback about the distribution of stimulation-induced paresthesia. The present study compared efficacy of first-time electrode placement under awake conditions with that of neurophysiologically guided placement under general anesthesia. METHODS: A retrospective review was performed of 387 SCS surgeries among 259 patients which included 167 new stimulator implantation to determine whether first time awake surgery for placement of spinal cord stimulators is preferable to non-awake placement. RESULTS: The incidence of device failure for patients implanted using neurophysiologically guided placement under general anesthesia was one-half that for patients implanted awake (14.94% vs. 29.7%). CONCLUSION: Non-awake surgery is associated with fewer failure rates and therefore fewer re-operations, making it a viable alternative. Any benefits of awake implantation should carefully be considered in the future.