Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy.

OBJECTIVE: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years. METHODS: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory. RESULTS: Of 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-tailed χ2). CONCLUSIONS: Adjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low. CLINICALTRIALSGOV IDENTIFIER: NCT00572195. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.

Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

OBJECTIVE: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin. METHODS: Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. RESULTS: There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.

Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy.

OBJECTIVE: Evaluate the seizure-reduction response and safety of mesial temporal lobe (MTL) brain-responsive stimulation in adults with medically intractable partial-onset seizures of mesial temporal lobe origin. METHODS: Subjects with mesial temporal lobe epilepsy (MTLE) were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. RESULTS: There were 111 subjects with MTLE; 72% of subjects had bilateral MTL onsets and 28% had unilateral onsets. Subjects had one to four leads placed; only two leads could be connected to the device. Seventy-six subjects had depth leads only, 29 had both depth and strip leads, and 6 had only strip leads. The mean follow-up was 6.1 ± (standard deviation) 2.2 years. The median percent seizure reduction was 70% (last observation carried forward). Twenty-nine percent of subjects experienced at least one seizure-free period of 6 months or longer, and 15% experienced at least one seizure-free period of 1 year or longer. There was no difference in seizure reduction in subjects with and without mesial temporal sclerosis (MTS), bilateral MTL onsets, prior resection, prior intracranial monitoring, and prior vagus nerve stimulation. In addition, seizure reduction was not dependent on the location of depth leads relative to the hippocampus. The most frequent serious device-related adverse event was soft tissue implant-site infection (overall rate, including events categorized as device-related, uncertain, or not device-related: 0.03 per implant year, which is not greater than with other neurostimulation devices). SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including patients with unilateral or bilateral MTLE who are not candidates for temporal lobectomy or who have failed a prior MTL resection.

Long-term outcome in occipital nerve stimulation patients with medically intractable primary headache disorders.

INTRODUCTION: €‚ Occipital nerve stimulation (ONS) may provide relief for refractory headache disorders. However, scant data exist regarding long-€term ONS outcomes. METHODS: €‚ The methods used were retrospective review of the medical records of all (nonindustry study) patients who were trialed and implanted with occipital nerve stimulator systems at our institution, followed by a phone interview. Up to three attempts were made to contact each patient, and those who were contacted were given the opportunity to participate in a brief phone interview regarding their ONS experience. Data for analysis were gleaned from both the phone interview and the patient's medical records. RESULTS: €‚ Twenty-nine patients underwent a trial of ONS during the 8.5-€year study period. Three patients did not go on to permanent implant, 12 could not be contacted, and 14 participated in the phone interview. Based upon the phone interview (if the patient was contacted) or chart review, ONS was deemed successful in five of the 12 migraine, four of the five cluster headache, and five of the eight miscellaneous headache patients, and therapy was documented as long as 102 months. In one of the 26 patients, success of ONS could not be determined. Among patients deemed to have successful outcomes, headache frequency decreased by 18%, severity by 27%, and migraine disability score by 50%. Fifty-€eight percent of patients required at least one lead revision. DISCUSSION: €‚ These results, although limited by their retrospective nature, suggest that ONS can be effective long term despite technical challenges. The number of patients within each headache subtype was insufficient to draw conclusions regarding the differential effect of ONS. CONCLUSIONS: €‚ Randomized controlled long-€term studies in specific, intractable, primary headache disorders are indicated.

Revision of occipital nerve stimulator leads: technical note of two techniques.

OBJECTIVE: Occipital nerve stimulation can be effective therapy for recalcitrant headache disorders. Lead migration remains the primary technical adverse event associated with this therapy. Revision surgery for occipital nerve stimulator leads sometimes requires exposure of all components including internal pulse generator, extension cables, connectors, and leads with multiple incisions. However, minimizing the invasiveness of revision surgery reduces the time, infection risk, and discomfort associated with the procedure. We describe two techniques that attempt to minimize the extent of revision surgery necessary for lead migration. MATERIALS AND METHODS: We describe two minimally invasive revision techniques. One uses a 14-gauge Tuohy needle converted to a slotted needle. The other uses a standard Tuohy needle inserted subcutaneously into the anchor site along the desired course of the lead. RESULTS: Both techniques allow replacement of a migrated occipital nerve stimulator lead while eliminating the need to access connector or battery sites with multiple incisions. CONCLUSIONS: When migration occurs, the techniques described can simplify lead revision while minimizing the invasiveness of the procedure.

Occipital nerve stimulation: technical and surgical aspects of implantation.

Occipital nerve stimulation may provide pain relief for patients with otherwise refractory primary headache disorders. While this treatment modality remains an off-label use of spinal cord stimulator technology, a growing body of literature documents surgical techniques, stimulation parameters, complications, and outcome of this novel form of neuromodulation. This chapter will review occipital nerve stimulation, including surgical techniques and complications noted in the literature. A discussion of stimulation parameters used for occipital stimulation will be included. Prospective, blinded studies of occipital nerve stimulation may clarify the role of occipital stimulation in chronic headache management.

Occipital nerve stimulator placement via a retromastoid to infraclavicular approach: a technical report.

Occipital nerve stimulation is a form of peripheral nerve stimulation used to treat refractory headache disorders. Various techniques have been described for occipital nerve stimulator implantation; these include midline cervical or retromastoid lead insertion with internal pulse generator placement in the infraclavicular, gluteal or low abdominal regions. Lead migration is one of the most common complications of occipital nerve stimulators. Implantation approaches that include remote battery sites may contribute to mechanical stress on the components, as the leads or extensions may traverse highly mobile body regions. In this technical report, we describe an occipital stimulator implantation technique that may be advantageous in terms of patient positioning, ease of surgical approach and minimization of mechanical stress on components.

Occipital nerve stimulator lead pathway length changes with volunteer movement: an in vitro study.

BACKGROUND: Occipital nerve stimulation is a modality reserved for refractory headache disorders. Leads (wires) are inserted subcutaneously in the occipital region to stimulate the distal C1-3 nerves; lead migration may result from repeated mechanical forces on the lead associated with patient movement. The primary aim of this study was to determine implantation pathways associated with the least pathway length change secondary to body movement in an in vitro model of an occipital stimulator system. METHODS: After institutional review board approval, 10 volunteers were recruited. The expected pathway of an occipital stimulator system was identified and measured externally, and then changes in pathway length were measured during various volunteer movements, including neck and low back flexion, extension, rotation, and lateral flexion. The pathways studied included those that connect internal pulse generators in the gluteal, low abdominal, and infraclavicular regions to occipital leads inserted via a cervical or retromastoid approach. RESULTS: The flexion/extension pathway length changes associated with midline occipital and retromastoid sites to the infraclavicular site were significantly less than those pathways to the periscapular site. Also, the abdominal site was associated with less pathway length change during flexion/extension than the gluteal site. CONCLUSIONS: Internal pulse generators in sites other than the buttock, including infraclavicular or low abdomen, may be associated with lower lead migration risk. There are many considerations when selecting insertion sites and lead pathways for occipital nerve stimulation. Implanters and patients may consider these results when contemplating surgical approaches to this challenging form of peripheral nerve stimulation.

Occipital nerve stimulator placement under general anesthesia: initial experience with 5 cases and review of the literature.

Anesthesiologists support nerve stimulator insertion procedures, including occipital nerve stimulator placement for refractory headache disorders. Sedation during these cases can be challenging on account of variable surgical stimuli and surgery positioning that contribute to neck flexion, potentially compromising the airway. Greater patient comfort and safety may be found in performing permanent occipital stimulator placement procedures entirely under general anesthesia, assuming that appropriate stimulation patterns can be achieved in patients who are unable to provide intraoperative feedback. The purpose of this study is to describe our initial experience with occipital nerve stimulator placement performed entirely under general anesthesia and the resulting stimulation patterns, and to review the medical literature regarding the anesthetic techniques used during these novel neurosurgical procedures. After institutional review board approval, we reviewed the records of 5 patients who underwent permanent occipital nerve stimulator placement under general anesthesia. Appropriateness of the postoperative stimulation patterns was noted in addition to complications. The medical literature was searched for occipital stimulation surgery studies that also described the anesthetic technique. We found that all 5 patients underwent uncomplicated general anesthetics. Postoperative occipital stimulation was nonpainful and symmetrical for all. The literature search provided little information on the anesthetic technique; most procedures were performed at least in part under local anesthesia with sedation. On the basis of this small case series, we conclude that the occipital nerve stimulator systems can be successfully placed under general anesthesia while still achieving the desired occipital region stimulation. Further studies are needed to correlate occipital nerve stimulator placement under general anesthesia and long-term headache control.

Quality: the Mayo Clinic approach.

Developing highly reliable care for patients requires changes in some traditional beliefs of medical practice, an evolution toward a "system" of health care, the disciplined application of scientific principles, modifications in the way all future providers are trained, and a fundamental understanding by leadership that quality must become a business strategy and core work, not an expense or regulatory requirement. Quality at Mayo is defined as a composite of outcomes, safety, and service. A 4-part strategic construct focusing on Culture, Infrastructure, Engineering, and Execution has been developed to guide improvement activities and to ensure a comprehensive approach to better patient care. The Mayo Clinic experience has led to a greater understanding of the leadership commitment, organizational challenges, and the breadth of initiatives necessary to achieve highly reliable care.

Greater occipital nerve stimulation via the Bion microstimulator: implantation technique and stimulation parameters. Clinical trial: NCT00205894.

BACKGROUND: Millions of patients suffer from medically refractory and disabling primary headache disorders. This problem has led to a search for new and innovative treatment modalities, including neuromodulation of the occipital nerves. OBJECTIVES: The primary aim of this study is to describe an implantation technique for the Bion microstimulator and document stimulation parameters and stimulation maps after Bion placement adjacent to the greater occipital nerve. The secondary aim is to document outcome measures one year post-implant. DESIGN: Prospective, observational feasibility study. METHODS: Nine patients with medically refractory primary headache disorders participated in this study. Approximately 6 months after Bion insertion, stimulation parameters and maps were documented for all patients. At one year, outcome measures were collected including the Migraine Disability Assessment Score. RESULTS: At 6 months, the mean perception threshold was 0.47 mA, while the mean discomfort threshold was 6.8 mA (stimulation range 0.47-6.8 mA). The mean paresthesia threshold was 1.64 mA and the mean usage range was 16.0. There were no major complications reported such as device migration, infection, or erosion. One patient stopped using her Bion before the 12-month follow-up visit. At one year, 7 of the 8 patients were judged as having obtained fair or better results in terms of reduction of disability; 5 patients had greater than a 90% reduction in disability. LIMITATIONS: Small, heterogeneous patient population without control group. Not blinded or randomized. CONCLUSION: The Bion can be successfully inserted adjacent to the greater occipital nerve in an effort to treat refractory primary headache disorders. This microstimulator may provide effective occipital stimulation and headache control while minimizing the risks associated with percutaneous or paddle leads implanted subcutaneously in the occipital region.

Percutaneous occipital stimulator lead tip erosion: report of 2 cases.

Occipital nerve stimulation is an emerging treatment modality for refractory headache disorders like migraine and cluster headache. Either percutaneous or surgical leads are implanted subcutaneously in the occipital region in an effort to stimulate the distal branches of the occipital nerves (C2-3). A number of complications of this technique have been reported, such as painful direct muscle stimulation and lead migration. We report the first 2 cases of occipital lead erosion. In both cases, the lead erosion occurred many months after implantation. One patient lost a significant amount of weight between the time of implant and lead erosion, while the other patient had no obvious risk factors. One patient underwent lead removal with reimplantation 1 month later; the other was managed with excision of a granuloma at the erosion site and prophylactic antibiotics. Both patients returned to excellent headache control. Lead erosion is a possible complication of occipital stimulation; strategies to reduce the risk of lead erosion are discussed, although further studies are needed to clarify the best surgical techniques.

Occipital nerve stimulation: technical and surgical aspects of implantation.

The objective of this article is to review the surgical aspects of occipital stimulation. Since 1999 there has been a growing interest in neuromodulation of the distal branches of C2-3 in an effort to treat refractory headache disorders. This is accomplished via implantation of subcutaneous electrodes to stimulate peripheral nerves in the occipital region. "Occipital nerve stimulation" is a term generically used to describe the technique. Mechanisms and outcome of this modality are beyond the scope of this review, which will focus on the technical aspects of the procedure with its associated complications such as lead migration, localized pain, and infection. The history of peripheral nerve and spinal cord stimulation as pain treatment modalities will be briefly reviewed. The equipment and surgical technique for both trial and permanent implantation of occipital nerve stimulators will be described, in addition to patient selection considerations. The available literature will be summarized and a discussion of future directions will be provided. Occipital nerve stimulation may be an effective minimally invasive treatment modality for refractory headache disorders; clearly, further studies are needed.