Ethical Considerations in the Implantation of Neuromodulatory Devices.

OBJECTIVES: Neuromodulatory devices are increasingly used by neurosurgeons to manage a variety of chronic conditions. Given their potential benefits, it is imperative to create clear ethical guidelines for the use of these devices. We present a tiered ethical framework for neurosurgeon recommendations for the use of neuromodulatory devices. MATERIALS AND METHODS: We conducted a literature review to identify factors neurosurgeons should consider when choosing to offer a neuromodulatory device to a patient. RESULTS: Neurosurgeons must weigh reductions in debilitating symptoms, improved functionality, and preserved quality of life against risks for intraoperative complications and adverse events due to stimulation or the device itself. Neurosurgeons must also evaluate whether patients and families will maintain responsibility for the management of neuromodulatory devices. Consideration of these factors should occur on an axis of resource allocation, ranging from provision of neuromodulatory devices to those with greatest potential benefit in resource-limited settings to provision of neuromodulatory devices to all patients with indications in contexts without resource limitations. Neurosurgeons must also take action to promote device effectiveness throughout the duration of care. CONCLUSIONS: Weighing risks and benefits of providing neuromodulatory devices and assessing ability to remain responsible for the devices on the level of the individual patient indicate which patients are most likely to achieve benefit from these devices. Consideration of these factors on an axis of resource allocation will allow for optimal provision of neuromodulatory devices to patients in settings of varied resources. Neurosurgeons play a primary role in promoting the effectiveness of these devices.

Factors Associated With Implantable Pulse Generator Site Pain: A Multicenter Cross-Sectional Study.

OBJECTIVES: Implantable pulse generator (IPG) site pain following neuromodulation procedures is a recognized complication. The site of the IPG placement varies depending on the neuromodulation type and physician preference. The incidence of IPG site pain as a function of the site of IPG implantation has not been studied systematically. MATERIALS AND METHODS: We performed a multicenter cross-sectional survey of the incidence, severity, and quality of IPG site pain, location of the IPG, the pain management needs, functional impairment, and cosmetic appearance related to the IPG placement. Contingency table analysis was conducted for categorical variables, and logistic regression analysis and linear regression model was used. RESULTS: The survey response rate was 60.5% (n = 510). Overall, 31.0% of patients reported pain at the IPG site in the last 72 hours with 31.4% reporting moderate to severe pain and 7.6% reporting severe pain. Older age was inversely associated with IPG-related pain (OR = 0.97, 95% CI = 0.96-0.99, p = 0.001). IPG implantation site did not have a statistically significant interaction with IPG site pain (p > 0.05). The most important factor for IPG site-associated pain was having a spinal cord stimulator implanted as compared to a deep brain stimulator, or sacral nerve stimulator. Most subjects reported no functional impairment related to IPG site pain (91%), found the IPG site pain as expected (80%), and found IPG site cosmetic appearance as expected (96%). CONCLUSIONS: The incidence of IPG site pain is an important complication of invasive neuromodulation. The anatomic location of the IPG placement does not appear to affect the incidence or severity of IPG site pain. However, the presence of a pre-implant chronic pain disorder does appear to affect the frequency and severity of IPG site pain.

ACR Appropriateness Criteria® Movement Disorders and Neurodegenerative Diseases.

Movement disorders and neurodegenerative diseases are a variety of conditions that involve progressive neuronal degeneration, injury, or death. Establishing the correct diagnosis of a movement disorder or neurodegenerative process can be difficult due to the variable features of these conditions, unusual clinical presentations, and overlapping symptoms and characteristics. MRI has an important role in the initial assessment of these patients, although a combination of imaging and laboratory and genetic tests is often needed for complete evaluation and management. This document summarizes the imaging appropriateness data for rapidly progressive dementia, chorea, Parkinsonian syndromes, suspected neurodegeneration with brain iron accumulation, and suspected motor neuron disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Percutaneous peripheral nerve stimulation for the treatment of chronic neuropathic postamputation pain: a multicenter, randomized, placebo-controlled trial.

BACKGROUND AND OBJECTIVES: Chronic neuropathic pain is a common challenging condition following amputation. Recent research demonstrated the feasibility of percutaneously implanting fine-wire coiled peripheral nerve stimulation (PNS) leads in proximity to the sciatic and femoral nerves for postamputation pain. A multicenter, double-blinded, randomized, placebo-controlled study collected data on the safety and effectiveness of percutaneous PNS for chronic neuropathic pain following amputation. METHODS: Twenty-eight lower extremity amputees with postamputation pain were enrolled. Subjects underwent ultrasound-guided implantation of percutaneous PNS leads and were randomized to receive PNS or placebo for 4 weeks. The placebo group then crossed over and all subjects received PNS for four additional weeks. The primary efficacy endpoint evaluated the proportion of subjects reporting ≥50% pain reduction during weeks 1-4. RESULTS: A significantly greater proportion of subjects receiving PNS (n=7/12, 58%, p=0.037) demonstrated ≥50% reductions in average postamputation pain during weeks 1-4 compared with subjects receiving placebo (n=2/14, 14%). Two subjects were excluded from efficacy analysis due to eligibility changes. Significantly greater proportions of PNS subjects also reported ≥50% reductions in pain (n=8/12, 67%, p=0.014) and pain interference (n=8/10, 80%, p=0.003) after 8 weeks of therapy compared with subjects receiving placebo (pain: n=2/14, 14%; pain interference: n=2/13, 15%). Prospective follow-up is ongoing; four of five PNS subjects who have completed 12-month follow-up to date reported ≥50% pain relief. CONCLUSIONS: This work demonstrates that percutaneous PNS therapy may provide enduring clinically significant pain relief and improve disability in patients with chronic neuropathic postamputation pain. TRIAL REGISTRATION NUMBER: NCT01996254.

Human olfactory-auditory integration requires phase synchrony between sensory cortices.

Multisensory integration is particularly important in the human olfactory system, which is highly dependent on non-olfactory cues, yet its underlying neural mechanisms are not well understood. In this study, we use intracranial electroencephalography techniques to record neural activity in auditory and olfactory cortices during an auditory-olfactory matching task. Spoken cues evoke phase locking between low frequency oscillations in auditory and olfactory cortices prior to odor arrival. This phase synchrony occurs only when the participant's later response is correct. Furthermore, the phase of low frequency oscillations in both auditory and olfactory cortical areas couples to the amplitude of high-frequency oscillations in olfactory cortex during correct trials. These findings suggest that phase synchrony is a fundamental mechanism for integrating cross-modal odor processing and highlight an important role for primary olfactory cortical areas in multisensory integration with the olfactory system.

The Neurostimulation Appropriateness Consensus Committee (NACC) Safety Guidelines for the Reduction of Severe Neurological Injury.

INTRODUCTION: Neurostimulation involves the implantation of devices to stimulate the brain, spinal cord, or peripheral or cranial nerves for the purpose of modulating the neural activity of the targeted structures to achieve specific therapeutic effects. Surgical placement of neurostimulation devices is associated with risks of neurologic injury, as well as possible sequelae from the local or systemic effects of the intervention. The goal of the Neurostimulation Appropriateness Consensus Committee (NACC) is to improve the safety of neurostimulation. METHODS: The International Neuromodulation Society (INS) is dedicated to improving neurostimulation efficacy and patient safety. Over the past two decades the INS has established a process to use best evidence to improve care. This article updates work published by the NACC in 2014. NACC authors were chosen based on nomination to the INS executive board and were selected based on publications, academic acumen, international impact, and diversity. In areas in which evidence was lacking, the NACC used expert opinion to reach consensus. RESULTS: The INS has developed recommendations that when properly utilized should improve patient safety and reduce the risk of injury and associated complications with implantable devices. CONCLUSIONS: On behalf of INS, the NACC has published recommendations intended to reduce the risk of neurological injuries and complications while implanting stimulators.

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.

Placebo-Controlled Trial of Familiar Auditory Sensory Training for Acute Severe Traumatic Brain Injury: A Preliminary Report.

BACKGROUND: Sensory stimulation is often provided to persons incurring severe traumatic brain injury (TBI), but therapeutic effects are unclear. OBJECTIVE: This preliminary study investigated neurobehavioral and neurophysiological effects related to sensory stimulation on global neurobehavioral functioning, arousal, and awareness. METHODS: A double-blind randomized placebo-controlled trial where 15 participants in states of disordered consciousness (DOC), an average of 70 days after TBI, were provided either the Familiar Auditory Sensory Training (FAST) or Placebo of silence. Global neurobehavioral functioning was measured with the Disorders of Consciousness Scale (DOCS). Arousal and awareness were measured with the Coma-Near-Coma (CNC) scale. Neurophysiological effect was measured using functional magnetic resonance imaging (fMRI). RESULTS: FAST (n = 8) and Placebo (n = 7) groups each showed neurobehavioral improvement. Mean DOCS change (FAST = 13.5, SD = 8.2; Placebo = 18.9, SD = 15.6) was not different, but FAST patients had significantly (P = .049; 95% confidence interval [CI] = -1.51, -.005) more CNC gains (FAST = 1.01, SD = 0.60; Placebo = 0.25, SD = 0.70). Mixed-effects models confirm CNC findings (P = .002). Treatment effect, based on CNC, is large (d = 1.88, 95% CI = 0.77, 3.00). Number needed to treat is 2. FAST patients had more fMRI activation in language regions and whole brain (P values <.05) resembling healthy controls' activation. CONCLUSIONS: For persons with DOC 29 to 170 days after TBI, FAST resulted in CNC gains and increased neural responsivity to vocal stimuli in language regions. Clinicians should consider providing the FAST to support patient engagement in neurorehabilitation.

Preliminary framework for Familiar Auditory Sensory Training (FAST) provided during coma recovery.

Since there remains a need to examine the nature of the neural effect and therapeutic efficacy/effectiveness of sensory stimulation provided to persons in states of seriously impaired consciousness, a passive sensory stimulation intervention, referred to as the Familiar Auditory Sensory Training (FAST) protocol, was developed for examination in an ongoing, double-blind, randomized clinical trial (RCT). The FAST protocol is described in this article according to the preliminary framework, which is a synthesis of knowledge regarding principles of plasticity and capabilities of the human brain to automatically and covertly process sensory input. Feasibility issues considered during the development of the intervention are also described. To enable replication of this intervention, we describe procedures to create the intervention and lessons learned regarding the creation process. The potential effect of the intervention is illustrated using functional brain imaging of nondisabled subjects. This illustration also demonstrates the relevance of the rationale for designing the FAST protocol. To put the intervention within the context of the scientific development process, the article culminates with a description of the study design for the ongoing RCT examining the efficacy of the FAST protocol.

Deep brain stimulation and motor cortical stimulation for neuropathic pain.

Deep brain stimulation (DBS) is an important treatment option for neuropathic pain. DBS has a considerable history, and it can be used successfully for a wide number of pain syndromes. Epidural motor cortex stimulation (MCS) also is a treatment option for neuropathic pain. Less invasive than DBS, MCS has been rapidly adopted and studied since first described in 1991. A growing body of literature supports the use of MCS for facial pain, though further study to better define the mechanism of action and the most appropriate patient populations is ongoing.

Failure modes of spinal cord stimulation hardware.

OBJECT: Epidural spinal cord stimulation (SCS) is effective at treating refractory pain. The failure modes of the implanted hardware, however, have not been well studied. A better understanding of this could aid in improving the current procedure or designing future devices. METHODS: The authors reviewed electronic charts and operative reports of 289 patients who had undergone SCS implantation between 1998 and 2002 at the Cleveland Clinic Foundation. Data were collected on demographics, type of hardware, date of implantation procedure, indication for treatment, time to failure, and failure mode. Data were then analyzed to identify significant differences. A total of 577 procedures were performed, 43.5% of which involved revision or removal of SCS hardware. The most common indication was complex regional pain syndrome 1, and this was followed by failed-back surgery syndrome. The median number of procedures per patient was two. Approximately 80% of all leads were the percutaneous type. The majority (62%) of leads were placed in the thoracic region, and 33.5% of all leads required revision. Poor pain relief coverage was the most common indication for revision. Surgically implanted leads broke twice as often as percutaneous leads. In 46% of the patients, hardware revision was required, and multiple revisions were necessary in 22.5%. Three-way ANOVA revealed significant differences in failure mode rates according to location (cervical compared with thoracic, p = 0.037) and failure modes (p = 0.019). Laminotomy leads tended to break and migrate sooner than percutaneous leads. Thoracic leads became infected sooner than cervical leads. CONCLUSIONS: The results of this analysis of SCS hardware failures may be used as a basis for refining surgical technique and designing the next generation of SCS hardware.

Deep brain stimulation for movement disorders.

Movement disorders remain the primary indication for the use of intracranial neurostimulation techniques. This review will discuss the history of this technology as well as the mechanisms of action, current clinical indications, and future prospects for the treatment of movement disorders.

Precentral stimulation for chronic pain.

A decade of clinical experience has suggested that precentral stimulation is an option for patients with deafferentation as well as other chronic pain syndromes. Permanent complications are uncommon. More scientific evidence is warranted to understand the precise mechanisms for this treatment modality. A larger organized clinical trial is desired to establish the efficacy of precentral stimulation.

Simultaneous use of bilateral subthalamic nucleus stimulators and an implantable cardiac defibrillator. Case report.

Bilateral electrical stimulation of the subthalamic nucleus is being used with increasing frequency as a treatment for severe Parkinson disease (PD). Implantable cardiac defibrillators improve survival in certain high-risk patients with coronary artery disease and ventricular arrhythmias. Because of concern about possible interaction between these devices, deep brain stimulation (DBS) systems are routinely disconnected before defibrillators are implanted in patients with PD and arrhythmia. The authors report on a patient with bilateral subthalamic stimulators who underwent successful placement of an implantable defibrillator. Testing of the devices over a wide range of settings revealed no interaction. The patient subsequently underwent multiple episodes of cardioversion when the ventricular lead became dislodged. There was no evidence of adverse neurological effects, and interrogation of the DBS devices after cardioversion revealed no changes in stimulus parameters. The outcome in this case indicates that DBS systems may be safely retained in selected patients who require implantable cardiac defibrillators.

Irving S. Cooper and his role in intracranial stimulation for movement disorders and epilepsy.

Dr. Irving Cooper (1922-1985) was a pioneer in the field of functional neurosurgery. After years of treating patients with tremor by creating deep lesions with either anterior choroidal artery ligation or cryogenic thalamotomy, he began to utilize methods of electrical cerebral stimulation as treatment for a variety of disorders. Chronic cerebellar stimulation was employed for patients with epilepsy, cerebral palsy, and dystonia. While Dr. Cooper believed his results to be significant, there still remain many challenges to his claims. Later in his career, he placed deep brain electrodes in the internal capsule and thalamus for epilepsy and dystonia. His encouraging results from this small series were often overlooked. This paper reviews the science behind Dr. Cooper's work, his case series, and the controversies surrounding his results.