Incidence and Management of Hardware-Related Wound Infections in Spinal Cord, Peripheral Nerve Field, and Deep Brain Stimulation Surgery: A Single-Center Study.

INTRODUCTION: Neuromodulation using deep brain stimulation (DBS), spinal cord stimulation (SCS), and peripheral nerve field stimulation (PNFS) to treat neurological, psychiatric, and pain disorders is a rapidly growing field. Infections related to the implanted hardware are among the most common complications and result in health-related and economic burden. Unfortunately, conservative medical therapy is less likely to be successful. In this retrospective study, we aimed to identify characteristics of the infections and investigated surgical and antimicrobial treatments. METHODS: A retrospective analysis was performed of patients with an infection related to DBS, SCS, and/or PNFS hardware over an 8-year period at our institution. Data were analyzed for type of neurostimulator, time of onset of infection following the neurosurgical procedure, location, and surgical treatment strategy. Surgical treatment of infections consisted of either a surgical wound revision without hardware removal or a surgical wound revision with partial or complete hardware removal. Data were further analyzed for the microorganisms involved, antimicrobial treatment and its duration, and clinical outcome. RESULTS: Over an 8-year period, a total of 1,250 DBS, 1,835 SCS, and 731 PNFS surgeries were performed including de novo system implantations, implanted pulse generator (IPG) replacements, and revisions. We identified 82 patients with infections related to the neurostimulator hardware, representing an incidence of 3.09% of the procedures. Seventy-one percent of the patients had undergone multiple surgeries related to the neurostimulator prior to the infection. The infections occurred after a mean of 12.2 months after the initial surgery. The site of infection was most commonly around the IPG, especially in DBS and SCS. The majority (62.2%) was treated by surgical wound revision with simultaneous partial or complete removal of hardware. Microbiological specimens predominantly yielded Staphylococcus epidermidis (39.0%) and Staphylococcus aureus (35.4%). After surgery, antimicrobials were given for a mean of 3.4 weeks. The antimicrobial regime was significantly shorter in patients with hardware removal in comparison to those who only had undergone surgical wound revision. One intracranial abscess occurred. No cases of infection-related death, sepsis, bacteremia, or intraspinal abscesses were found. CONCLUSION: Our data did show the predominance of S. epidermidis and S. aureus as etiologic organisms in hardware-related infections. Infections associated with S. aureus most likely required (partial) hardware removal. Aggressive surgical treatment including hardware removal shortens the duration of antimicrobial treatment. Clear strategies should be developed to treat hardware-related infections to optimize patient management and reduce health- and economic-related burden.

Incidence and management of idiopathic peri-lead edema (IPLE) following deep brain stimulation (DBS) surgery: Case series and review of the literature.

OBJECTIVE: Idiopathic peri-lead edema (IPLE) is being increasingly described as a potential complication occurring after DBS surgery. Its incidence and relationship to post-operative symptoms, though, are still poorly defined and its understanding and management yet limited. METHODS: We reviewed delayed (≥ 72 h) post-operative CT imaging of patients who underwent DBS surgery at our Institution. A comparison of clinical and laboratory findings was carried out between patients with IPLE and controls. RESULTS: 61 patients, accounting for 115 electrodes, were included. Incidence of IPLE was 37.7 % per patient and 29.5 % per electrode. Patients with IPLE were significantly older than controls (52.82 ± 15.65 years vs 44.73 ± 18.82 years, p = 0.04). There was no difference in incidence of new-onset neurological symptoms between patients with IPLE and controls. Longer operative time (180.65 ± 34.30 min vs 158.34 ± 49.28 min, p = 0.06) and a greater number of MERs per electrode were associated with IPLE (3.37 ± 1.21 vs 3.00 ± 1.63, p = 0.089), though these comparisons did not meet the statistical significance. None of the patients with IPLE underwent hardware removal, with IPLE vanishing spontaneously over months. CONCLUSIONS: IPLE is an underestimated, benign event that may occur after DBS surgery. Age, longer operative time and MER use may represent risk factors for IPLE formation, but further studies are needed. The presence of post-operative neurological symptoms and fever was not associated with IPLE presence, highlighting its benign nature and suggesting that empiric treatment may not be always justified.

Developing Predictor Models of Postoperative Verbal Fluency After Deep Brain Stimulation Using Preoperative Neuropsychological Assessment.

BACKGROUND: Deep brain stimulation (DBS) for Parkinson disease provides significant improvement of motor symptoms but can also produce neurocognitive side effects. A decline in verbal fluency (VF) is among the most frequently reported side effects. Preoperative factors that could predict VF decline have yet to be identified. OBJECTIVE: To develop predictive models of DBS postoperative VF decline using a machine learning approach. METHODS: We used a prospective database of patients who underwent neuropsychological and VF assessment before both subthalamic nucleus (n = 47, bilateral = 44) and globus pallidus interna (n = 43, bilateral = 39) DBS. We used a neurobehavioral rating profile as features for modeling postoperative VF. We constructed separate models for action, semantic, and letter VF. We used a leave-one-out scheme to test the accuracy of the predictive models using median absolute error and correlation with actual postoperative scores. RESULTS: The predictive models were able to predict the 3 types of VF with high accuracy ranging from a median absolute error of 0.92 to 1.36. Across all three models, higher preoperative fluency, digit span, education, and Mini-Mental State Examination were predictive of higher postoperative fluency scores. By contrast, higher frontal system deficits, age, Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease scored by the patient, disease duration, and Behavioral Inhibition/Behavioral Activation Scale scores were predictive of lower postoperative fluency scores. CONCLUSION: Postoperative VF can be accurately predicted using preoperative neurobehavioral rating scores above and beyond preoperative VF score and relies on performance over different aspects of executive function.

Assessment of the Effect of Subthalamic Deep Brain Stimulation on Sleep Quality of Parkinson's Disease Patients.

AIM: To investigate the effects of subthalamic deep brain stimulation (STN DBS) therapy on sleep quality of Parkinson?s Disease (PD) patients and the relationship between sleep, motor symptoms, depression, and adverse effects of dopamine replacement therapies. MATERIAL AND METHODS: A total of 26 PD patients have been included and assessed using various tools both 1 week before and 8 months after the STN DBS therapy. The data collection tools were the Unified Parkinson?s Disease Rating Scale (UPDRS), Beck Depression Inventory (BDI), Montreal Cognitive Assessment (MoCA), Parkinson?s Disease Questionnaire (PDQ-39), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS) and Polysomnography. RESULTS: PSQI, ISI, and ESS scores were found to have significantly improved after the STN DBS therapy (p=0.002, p=0.006, p < 0.001, respectively), as were the scores obtained from several PSQI sub-scales, that is, sleep duration, sleep disturbance and daytime dysfunction (p=0.023, p=0.005, p=0.032, respectively). Additionally, Wake Times After Sleep Onset (WASO) (p=0.047) and Rapid Eye Movement (REM) sleep latency values (p=0.005) were found to have decreased after the STN DBS treatment, whereas REM sleep durations (p=0,028) and REM sleep percentages (p=0.007) were found to have increased, after the STN DBS therapy. No correlation was found between the ESS scores and Levodopa Equivalent Dosage (LED) or between the scores obtained from the sleep scales and the scores obtained from the UPDRS and BDI. There was also no correlation between sleep scores and other PD-related factors. CONCLUSION: The findings of this study indicated that STN DBS therapy positively affected the PD patients? sleep. This result was attributed to the neuromodulatory effects of the STN DBS independent of the motor symptoms, depression levels, and LED decrease.

Indication-based analysis of patient outcomes following deep brain stimulation surgery.

BACKGROUND: While considered a safe operation, deep brain stimulation (DBS) has been associated with various morbidities. We assessed differences in postsurgical complication rates in patients undergoing the most common types of neurostimulation surgery. METHODS: The National Readmission Database (NRD) was queried to identify patients undergoing neurostimulation placement with the diagnosis of Parkinson disease (PD), epilepsy, dystonia, or essential tremor (ET). Demographics and complications, including infection, pneumonia, and neurostimulator revision, were queried for each cohort and compiled. Readmissions were assessed in 30-, 90-, and 180-day intervals. We implemented nearest-neighbor propensity score matching to control for demographic and sample size differences between groups. RESULTS: We identified 3230 patients with Parkinson disease, 1289 with essential tremor, 965 with epilepsy, and 221 with dystonia. Following propensity score matching, 221 patients remained in each cohort. Readmission rates 30-days after hospital discharge for PD patients (15.5 %) were significantly greater than those for ET (7.8 %) and seizure patients (4.4 %). Pneumonia was reported for PD (1.6 %), seizure (3.3 %) and dystonia (1.7 %) patients but not individuals ET. No PD patients were readmitted at 30-days due to dysphagia while individuals treated for ET (6.5 %), seizure (1.6 %) and dystonia (5.2 %) were. DBS-revision surgery was performed for 11.48 % of PD, 6.52 % of ET, 1.64 % of seizure and 6.90 % of dystonia patients within 30-days of hospital discharge. CONCLUSION: 30-day readmission rates vary significantly between indications, with patients receiving DBS for PD having the highest rates. Further longitudinal studies are required to describe drivers of variation in postoperative outcomes following DBS surgery for different indications.

Assessment of the effect of continuous theta burst stimulation of the motor cortex on manual dexterity in non-human primates in a direct comparison with invasive intracortical pharmacological inactivation.

Non-invasive reversible perturbation techniques of brain output such as continuous theta burst stimulation (cTBS), commonly used to modulate cortical excitability in humans, allow investigation of possible roles in functional recovery played by distinct intact cortical areas following stroke. To evaluate the potential of cTBS, the behavioural effects of this non-invasive transient perturbation of the hand representation of the primary motor cortex (M1) in non-human primates (two adult macaques) were compared with an invasive focal transient inactivation based on intracortical microinfusion of GABA-A agonist muscimol. The effects on the contralateral arm produced by cTBS or muscimol were directly compared based on a manual dexterity task performed by the monkeys, the "reach and grasp" drawer task, allowing quantitative assessment of the grip force produced between the thumb and index finger and exerted on the drawer's knob. cTBS only induced modest to moderate behavioural effects, with substantial variability on manual dexterity whereas the intracortical muscimol microinfusion completely impaired manual dexterity, producing a strong and clear cortical inhibition of the M1 hand area. In contrast, cTBS induced mixed inhibitory and facilitatory/excitatory perturbations of M1, though with predominant inhibition. Although cTBS impacted on manual dexterity, its effects appear too limited and variable in order to use it as a reliable proof of cortical vicariation mechanism (cortical area replacing another one) underlying functional recovery following a cortical lesion in the motor control domain, in contrast to potent pharmacological block generated by muscimol infusion, whose application is though limited to an animal model such as non-human primate.

3-Tesla MRI of deep brain stimulation patients: safety assessment of coils and pulse sequences.

OBJECTIVE: Physicians are more frequently encountering patients who are treated with deep brain stimulation (DBS), yet many MRI centers do not routinely perform MRI in this population. This warrants a safety assessment to improve DBS patients' accessibility to MRI, thereby improving their care while simultaneously providing a new tool for neuromodulation research. METHODS: A phantom simulating a patient with a DBS neuromodulation device (DBS lead model 3387 and IPG Activa PC model 37601) was constructed and used. Temperature changes at the most ventral DBS electrode contacts, implantable pulse generator (IPG) voltages, specific absorption rate (SAR), and B1+rms were recorded during 3-T MRI scanning. Safety data were acquired with a transmit body multi-array receive and quadrature transmit-receive head coil during various pulse sequences, using numerous DBS configurations from "the worst" to "the most common."In addition, 3-T MRI scanning (T1 and fMRI) was performed on 41 patients with fully internalized and active DBS using a quadrature transmit-receive head coil. MR images, neurological examination findings, and stability of the IPG impedances were assessed. RESULTS: In the phantom study, temperature rises at the DBS electrodes were less than 2°C for both coils during 3D SPGR, EPI, DTI, and SWI. Sequences with intense radiofrequency pulses such as T2-weighted sequences may cause higher heating (due to their higher SAR). The IPG did not power off and kept a constant firing rate, and its average voltage output was unchanged. The 41 DBS patients underwent 3-T MRI with no adverse event. CONCLUSIONS: Under the experimental conditions used in this study, 3-T MRI scanning of DBS patients with selected pulse sequences appears to be safe. Generally, T2-weighted sequences (using routine protocols) should be avoided in DBS patients. Complementary 3-T MRI phantom safety data suggest that imaging conditions that are less restrictive than those used in the patients in this study, such as using transmit body multi-array receive coils, may also be safe. Given the interplay between the implanted DBS neuromodulation device and the MRI system, these findings are specific to the experimental conditions in this study.

Deep brain stimulation and treatment-resistant obsessive-compulsive disorder: A systematic review. / La estimulación cerebral profunda en el trastorno obsesivo-compulsivo refractario al tratamiento: una revisión sistemática.

INTRODUCTION: At least 10% of patients with Obsessive-compulsive Disorder (OCD) are refractory to psychopharmacological treatment. The emergence of new technologies for the modulation of altered neuronal activity in Neurosurgery, deep brain stimulation (DBS), has enabled its use in severe and refractory OCD cases. The objective of this article is to review the current scientific evidence on the effectiveness and applicability of this technique to refractory OCD. METHOD: We systematically reviewed the literature to identify the main characteristics of deep brain stimulation, its use and applicability as treatment for obsessive-compulsive disorder. Therefore, we reviewed PubMed/Medline, Embase and PsycINFO databases, combining the key-words 'Deep brain stimulation', 'DBS' and 'Obsessive-compulsive disorder' 'OCS'. The articles were selected by two of the authors independently, based on the abstracts, and if they described any of the main characteristics of the therapy referring to OCD: applicability; mechanism of action; brain therapeutic targets; efficacy; side-effects; co-therapies. All the information was subsequently extracted and analysed. RESULTS: The critical analysis of the evidence shows that the use of DBS in treatment-resistant OCD is providing satisfactory results regarding efficacy, with assumable side-effects. However, there is insufficient evidence to support the use of any single brain target over another. Patient selection has to be done following analyses of risks/benefits, being advisable to individualize the decision of continuing with concomitant psychopharmacological and psychological treatments. CONCLUSIONS: The use of DBS is still considered to be in the field of research, although it is increasingly used in refractory-OCD, producing in the majority of studies significant improvements in symptomatology, and in functionality and quality of life. It is essential to implement random and controlled studies regarding its long-term efficacy, cost-risk analyses and cost/benefit.

Application of the Six Sigma concept for quality assessment of different strategies in DBS surgery.

BACKGROUND: For quality analysis, we applied the Six Sigma concept to define quality indicators and their boundaries as well as to compare treatment-dependent outcome data of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD). METHODS: The Unified Parkinson Disease Rating Scale (UPDRS) III with on medication and on stimulation, the reduction of daily levodopa equivalence doses (LED), and the stimulation amplitude 1 year after surgery were registered. Regarding the results of the EARLYSTIM study, sigma values for applicable studies were calculated and compared. Further, the impact of perioperative conditions on patients' outcomes was analyzed. RESULTS: Forty-one studies with 2184 patients were included. The bleeding risk was 1.36%. In median, UPDRS III on/on improved by 19.9% while the LED was reduced by 45.2%. The median stimulation amplitude was 2.84 V. With the Six Sigma principle, a comparison between different centers was possible. Microelectrode recordings (MER) did not correlate with occurrence of bleedings and did not impact patient outcome. CONCLUSIONS: The Six Sigma principle can be simply used to analyze, improve and compare complex medical processes, particularly, the DBS surgery. Based on these data, higher sigma values were reached for clinical improvement in UPDRS III on/on for patients who underwent surgery in local anesthesia with intraoperative test stimulation compared to surgery in general anesthesia. However, the difference was not statistically significant. Application of MER was found to be optional with no increased bleeding risk and no improvement on patient's outcome.

Brain Shift and Pneumocephalus Assessment During Frame-Based Deep Brain Stimulation Implantation With Intraoperative Magnetic Resonance Imaging.

BACKGROUND: Brain shift and pneumocephalus are major concerns regarding deep brain stimulation (DBS). OBJECTIVE: To report the extent of brain shift in deep structures and pneumocephalus in intraoperative magnetic resonance imaging (MRI). METHODS: Twenty patients underwent bilateral DBS implantation in an MRI suite. Volume of pneumocephalus, duration of procedure, and 6 anatomic landmarks (anterior commissure, posterior commissure, right fornix [RF], left fornix [LF], right putaminal point, and left putaminal point) were measured. RESULTS: Pneumocephalus varied from 0 to 32 mL (median = 0.6 mL). Duration of the procedure was on average 195.5 min (118-268 min) and was not correlated with the amount of pneumocephalus. There was a significant posterior displacement of the anterior commissure (mean = -1.1 mm, P < .001), RF (mean = -0.6 mm, P < .001), LF (mean = -0.7 mm, P < .001), right putaminal point (mean = -0.9 mm, P = .001), and left putaminal point (mean = -1.0 mm, P = .001), but not of the posterior commissure (mean = 0.0 mm, P = .85). Both RF (mean = -.7 mm, P < .001) and LF (mean = -0.5 mm, P < .001) were posteriorly displaced after a right-sided burr hole. There was a correlation between anatomic landmarks displacement and pneumocephalus after 2 burr holes (rho = 0.61, P = .007), but not after 1 burr hole (rho = 0.16, P = .60). CONCLUSION: Better understanding of how pneumocephalus displaces subcortical structures can significantly enhance our intraoperative decision making and overall targeting strategy.

Assessment of Safety and Outcome of Lateral Hypothalamic Deep Brain Stimulation for Obesity in a Small Series of Patients With Prader-Willi Syndrome.

Importance: Deep brain stimulation (DBS) has been investigated for treatment of morbid obesity with variable results. Patients with Prader-Willi syndrome (PWS) present with obesity that is often difficult to treat. Objective: To test the safety and study the outcome of DBS in patients with PWS. Design, Setting, and Participants: This case series was conducted in the Hospital das Clínicas, University of São Paulo, Brazil. Four patients with genetically confirmed PWS presenting with severe obesity were included. Exposure: Deep brain stimulation electrodes were bilaterally implanted in the lateral hypothalamic area. After DBS implantation, the treatment included the following phases: titration (1-2 months), stimulation off (2 months), low-frequency DBS (40 Hz; 1 month), washout (15 days), high-frequency DBS (130 Hz; 1 month), and long-term follow-up (6 months). Main Outcomes and Measures: Primary outcome measures were adverse events recorded during stimulation and long-term DBS treatment. Secondary outcomes consisted of changes in anthropometric measures (weight, body mass index [calculated as weight in kilograms divided by height in meters squared], and abdominal and neck circumference), bioimpedanciometry, and calorimetry after 6 months of treatment compared with baseline. The following evaluations and measurements were conducted before and after DBS: clinical, neurological, psychiatric, neuropsychological, anthropometry, calorimetry, blood workup, hormonal levels, and sleep studies. Adverse effects were monitored during all follow-up visits. Results: Four patients with PWS were included (2 male and 2 female; ages 18-28 years). Baseline mean (SD) body mass index was 39.6 (11.1). Two patients had previous bariatric surgery, and all presented with psychiatric comorbidity, which was well controlled with the use of medications. At 6 months after long-term DBS, patients had a mean 9.6% increase in weight, 5.8% increase in body mass index, 8.4% increase in abdominal circumference, 4.2% increase in neck circumference, 5.3% increase in the percentage of body fat, and 0% change in calorimetry compared with baseline. Also unchanged were hormonal levels and results of blood workup, sleep studies, and neuropsychological evaluations. Two patients developed stimulation-induced manic symptoms. Discontinuation of DBS controlled this symptom in 1 patient. The other required adjustments in medication dosage. Two infections were documented, 1 associated with skin picking. Conclusions and Relevance: Safety of lateral hypothalamic area stimulation was in the range of that demonstrated in patients with similar psychiatric conditions receiving DBS. In the small cohort of patients with PWS treated in our study, DBS was largely ineffective.

Cost of Deep Brain Stimulation Infection Resulting in Explantation.

BACKGROUND: Deep brain stimulation (DBS) hardware infection is a serious complication, often resulting in multiple hardware salvage attempts, hospitalizations, and long-term antibiotic therapy. OBJECTIVES: We aimed to quantify the costs of DBS hardware-related infections in patients undergoing eventual device explantation. METHODS: Of 362 patients who underwent 530 electrode placements (1 January 2010 to 30 December 2014), 16 (4.4%) had at least 2 hardware salvage procedures. Most (n = 15 [93.8%]) required complete explantation due to recurrent infection. Financial data (itemized hospital and physician costs) were available for 13 patients and these were analyzed along with the demographic data. RESULTS: Each patient underwent 1-5 salvage procedures (mean 2.5 ± 1.4; median 2). The mean total cost for a patient undergoing the median number of revisions (n = 2), device explantation, and subsequent reimplantation after infection clearance was USD 75,505; just over half this cost (54.2% [USD 40,960]) was attributable to reimplantation, and nearly one-third (28.9% [USD 21,816]) was attributable to hardware salvage procedures. Operating-room costs were the highest cost category for hardware revision and explantation. Medical and surgical supplies accounted for the highest reimplantation cost. CONCLUSIONS: DBS infection incurs significant health care costs associated with hardware salvage attempts, explantation, and reimplantation. The highest cost categories are operating-room services and medical and surgical supplies.

Assessment of individual cognitive changes after deep brain stimulation surgery in Parkinson's disease using the Neuropsychological Test Battery Vienna short version.

Long-term therapy of Parkinson's disease with L­DOPA is associated with a high risk of developing motor fluctuations and dyskinesia. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can improve these motor complications. Although the positive effect on motor symptoms has been proven, postoperative cognitive decline has been documented. To tackle the impact of DBS on cognition, 18 DBS patients were compared to 25 best medically treated Parkinson's patients, 24 patients with mild cognitive impairment (MCI) and 12 healthy controls using the Neuropsychological Test Battery Vienna short version (NTBV-short) for cognitive outcome 12 months after the first examination. Reliable change index methodology was used. Roughly 10% of DBS patients showed cognitive decline mainly affecting the domains attention and executive functioning (phonemic fluency). Further research is needed to identify the mechanisms that lead to improvement or deterioration of cognitive functions in individual cases.

Deep Brain Stimulation as a Treatment for Refractory Epilepsy: Review of the Current State-of-the-Art.

Epilepsy affects ∼ 1% of the global population, and 33% of patients are nonresponsive to medication and must seek alternative treatment options. Alternative options such as surgery and ablation exist but are not appropriate treatment plans for some patients. Neurostimulation methods such as vagal nerve stimulation, responsive neural stimulation, and deep brain stimulation (DBS) are viable alternatives for medically refractory patients. DBS stimulation has been used in the treatment of Parkinson's disease, dystonia, and pain management. For the treatment of epilepsy, DBS has been found to be an effective treatment plan, with promising results of reduced seizure frequency and intensity. In this review, we discuss DBS surgery and equipment, mechanisms of DBS for epilepsy, and efficacy, technological specifications, and suggestions for future research. We also review a historical summary of experiments involving DBS for epilepsy. Our literature review suggests that further studies are warranted for medically refractory epilepsy using DBS.

Cost-utility analysis of deep brain stimulation surgery plus best medical therapy versus best medical therapy in patients with Parkinson's: Economic evaluation alongside the PD SURG trial.

INTRODUCTION: Williams and colleagues reported that DBS surgery for patients with advanced PD improves motor function and quality of life compared to best medical therapy alone at 1 year, but with surgery-related side effects in a minority. This article reports on the economic evaluation alongside this trial. METHODS: Detailed resource use and quality of life over 12 months after randomization was obtained from the trial reported by Williams and colleagues. Outcomes were measured using the EQ-5D and quality-adjusted life years calculated. RESULTS: Year 1 costs for surgery were significantly higher than in best medical therapy, at £19,069 compared to £9,813, a difference of £9,256 (95% confidence interval [CI]: £7,625, £10,887). There was a small, significant gain in utility at 1 year but a statistically insignificant gain of 0.02 quality-adjusted life years (95% CI: -0.015, 0.05) in the surgical arm. The incremental cost per quality-adjusted life year of surgery at 1 year was £468,528. Extrapolation reveals that after 5 years, this ratio is likely to reduce to £45,180, but subsequently rise to £70,537 at 10 years owing to the increased probability of battery replacements (and re-replacements) beyond 5 years. CONCLUSION: In this patient group, DBS is not cost-effective at 1 year. Extrapolation, however, reveals an increasing likelihood of cost-effectiveness up to 5 years and reducing cost-effectiveness between 5 and 10 years. These models are sensitive to assumptions about future costs and quality-adjusted life years gained. © 2016 International Parkinson and Movement Disorder Society.

Risk assessment of magnetic resonance imaging in chronically implanted paddle electrodes for cortical stimulation.

BACKGROUND: Cortical epidural stimulation is used for the treatment of different neuropsychiatric disorders such as chronic neuropathic pain, tinnitus, movement disorders, and psychiatric diseases. While preoperative magnetic resonance imaging (MRI) is considered the imaging tool of choice for planning the approach and electrode placement, postoperative MRI is still a contraindication with implanted paddle leads due to the risk of thermal damage or current induction creating seizures or neurological deficits. OBJECTIVES: In this feasibility in vitro study the temperature changes and induction were determined as well as the artifacts caused by 2 parallel paddle leads (Resume II, Model 3587 A; Medtronic, Minneapolis, Minn., USA), commonly used in clinical practice with and without a pulse generator (Prime Advanced, Model 7489; Medtronic). METHODS: An ultrasound gel-filled head phantom with 2 paddle leads mimicking the surgical scenario was used to evaluate temperature changes as well as induced currents in a 1.5- and 3-tesla MR scanner. In addition, 1 patient underwent a 3-tesla MRI with an implanted subdural paddle lead. RESULTS: Negligible temperature changes were detected with turbo spin echo sequences in the 1.5- and 3-tesla scanner using a head and body coil. Induced voltages up to 6 V were measured. The imaging artifacts in the phantom were well tolerable. The patient's imaging was uneventful under the settings which are accepted for deep brain stimulation imaging. CONCLUSION: MRI under the conditions described here seems to be safe with the implants used in this study. In particular, the induced temperature is much lower with paddle compared to conventional leads due to the different electrode design. The induced voltage does not carry any risks. However, these findings cannot automatically be transferred to other implants or other scanning conditions, and further studies are needed. The biomedical companies should be encouraged to develop MR-conditional paddle leads. Also, further research is necessary to study the mechanism of action of cortical stimulation in the future.

The appropriate use of neurostimulation: stimulation of the intracranial and extracranial space and head for chronic pain. Neuromodulation Appropriateness Consensus Committee.

INTRODUCTION: The International Neuromodulation Society (INS) has identified a need for evaluation and analysis of the practice of neurostimulation of the brain and extracranial nerves of the head to treat chronic pain. METHODS: The INS board of directors chose an expert panel, the Neuromodulation Appropriateness Consensus Committee (NACC), to evaluate the peer-reviewed literature, current research, and clinical experience and to give guidance for the appropriate use of these methods. The literature searches involved key word searches in PubMed, EMBASE, and Google Scholar dated 1970-2013, which were graded and evaluated by the authors. RESULTS: The NACC found that evidence supports extracranial stimulation for facial pain, migraine, and scalp pain but is limited for intracranial neuromodulation. High cervical spinal cord stimulation is an evolving option for facial pain. Intracranial neurostimulation may be an excellent option to treat diseases of the nervous system, such as tremor and Parkinson's disease, and in the future, potentially Alzheimer's disease and traumatic brain injury, but current use of intracranial stimulation for pain should be seen as investigational. CONCLUSIONS: The NACC concludes that extracranial nerve stimulation should be considered in the algorithmic treatment of migraine and other disorders of the head. We should strive to perfect targets outside the cranium when treating pain, if at all possible.

Neurohistopathological findings at the electrode-tissue interface in long-term deep brain stimulation: systematic literature review, case report, and assessment of stimulation threshold safety.

OBJECTIVES: Despite the widespread use of deep brain stimulation (DBS) in the treatment of neurologic disorders for over a quarter of a century, there has not been a systematic review and analyses of cases in which long-term postmortem clinic-pathologic data have been collected demonstrating the effects of chronically implanted electrodes and electrical stimulation on human brain tissue. Our objective is to provide a comprehensive systematic review of the literature on clinicopathologic findings of DBS tissue-electrode interface (TEI) and to determine types and prevalences of neuropathological findings among electrode materials and stimulation parameters and to augment this with previously unpublished histopathological data, images, and analyses from a DBS case implanted for 12 years, providing the longest duration histopathological follow-up. MATERIALS AND METHODS: A Medline literature review identified DBS cases upon which postmortem clinicopathologic follow-up was performed with adequate characterization of TEI. Direct follow-up with authors augmented this with unpublished data and neuropathological details. RESULTS: We identified 40 cases, mean age 59.1 ± 13.0 (range: 21-88) years, involving 58 implanted DBS electrodes. The mean postmortem histopathological follow-up of the implanted DBS electrodes was 22.2 ± 29.2 (range: 0.067-146) months, including our case with a 12-year follow-up. The following histological changes were identified: fibrous sheaths (5-25 µm thickness) surrounding the electrode (94%), fibrillary gliosis (73%), reactive astrocytes (78%), multinucleated giant cells (75%), mononuclear leukocytes (92%), and macrophages (91%). Microglial activation (60%), axonal spheroids (64%), and neuronal loss (60%) were less common and absent at 12-year follow-up in the index case. This is seventh case reporting T cell presence at the TEI. CONCLUSIONS: Neuropathological findings from published cases and our 12-year follow-up index case confirm the long-term safety of neuromodulation and stimulation thresholds and demonstrate persistence of T cells and occasional subclinical focal tissue injury.

Risks of common complications in deep brain stimulation surgery: management and avoidance.

OBJECT: Deep brain stimulation (DBS) surgery is increasingly prominent in the treatment of various disorders refractory to medication. Despite the procedure's efficacy, the community at large continues to be hesitant about presumed associated risks. The main object of this study was to assess the incidence of various surgical complications occurring both during and after DBS device implantation in a large population of patients with movement disorders in an effort to better quantify patient risk, define management plans, and develop methods for risk avoidance. A second aim was to corroborate the low procedural complication risk of DBS reported by others, which in light of the procedure's efficacy is needed to promote its widespread acceptance. METHODS: All patients who had undergone new DBS device implantation surgery between 2002 and 2010 by a single surgeon were entered into a database after being verified by cross-referencing manufacturer implantation records. All surgical records and charts were reviewed to identify intraoperative, perioperative, and long-term surgical complications, including any characteristics predictive of an adverse event. RESULTS: Seven hundred twenty-eight patients received 1333 new DBS electrodes and 1218 new internal pulse generators (IPGs) in a total of 1356 stereotactic procedures for the treatment of movement disorders. Seventy-eight percent of the patients had staged lead and IPG implantations. Of the 728 patients, 452 suffered from medically refractory Parkinson disease; in the other patients, essential tremor (144), dystonia (64), mixed disease (30), and other hyperkinetic movement disorders (38) were diagnosed. Severe intraoperative adverse events included vasovagal response in 6 patients (0.8%), hypotension in 2 (0.3%), and seizure in 2 (0.3%). Postoperative imaging confirmed asymptomatic intracerebral hemorrhage (ICH) in 4 patients (0.5%), asymptomatic intraventricular hemorrhage in 25 (3.4%), symptomatic ICH in 8 (1.1%), and ischemic infarction in 3 (0.4%), associated with hemiparesis and/or decreased consciousness in 13 (1.7%). Long-term complications of DBS device implantation not requiring additional surgery included hardware discomfort in 8 patients (1.1%) and loss of desired effect in 10 (1.4%). Hardware-related complications requiring surgical revision included wound infections in 13 patients (1.7%), lead malposition and/or migration in 13 (1.7%), component fracture in 10 (1.4%), component malfunction in 4 (0.5%), and loss of effect in 19 (2.6%). CONCLUSIONS: The authors confirmed that the overall risk of both procedure- and hardware-related adverse events is acceptably low. They offer advice on how to avoid the most common complications.

Electrical stimulation for drug-resistant epilepsy: an evidence-based analysis.

OBJECTIVE: The objective of this analysis was to evaluate the effectiveness of deep brain stimulation (DBS) and vagus nerve stimulation (VNS) for the treatment of drug-resistant epilepsy in adults and children. DATA SOURCES: A literature search was performed using MEDLINE, EMBASE, the Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published from January 2007 until December 2012. REVIEW METHODS: Systematic reviews, meta-analyses, randomized controlled trials (RCTs), and observational studies (in the absence of RCTs) of adults or children were included. DBS studies were included if they specified that the anterior nucleus of thalamus was the area of the brain stimulated. Outcomes of interest were seizure frequency, health resource utilization, and safety. A cost analysis was also performed. RESULTS: The search identified 6 studies that assessed changes in seizure frequency after electrical stimulation: 1 RCT on DBS in adults, 4 RCTs on VNS in adults, and 1 RCT on VNS in children. The studies of DBS and VNS in adults found significantly improved rates of seizure frequency, but the study of VNS in children did not find a significant difference in seizure frequency between the high and low stimulation groups. Significant reductions in hospitalizations and emergency department visits were found for adults and children who received VNS. No studies addressed the use of health resources for patients undergoing DBS. Five studies reported on adverse events, which ranged from serious to transient for both procedures in adults and were mostly transient in the 1 study of VNS in children. LIMITATIONS: We found no evidence on DBS in children or on health care use related to DBS. The measurement of seizure frequency is self-reported and is therefore subject to bias and issues of compliance. CONCLUSIONS: Based on evidence of low to moderate quality, both DBS and VNS seemed to reduce seizure frequency in adults. In children, VNS did not appear to be as effective at reducing seizure frequency, but children had significantly fewer hospitalizations and ED visits after VNS implantation. Despite the considerable risks associated with these invasive procedures, long-term adverse events appear to be limited. PLAIN LANGUAGE SUMMARY: Electrical stimulation of specific areas of the brain is a procedure used to control epileptic seizures when more conventional treatments are not working. Most adults and children with epilepsy are able to control their seizures with medication, but for some patients, drugs are not effective and surgery to remove the part of the brain where the seizures start is not an appropriate option. This study looked at the research available on the effectiveness, safety, and cost of two types of electrical stimulation devices currently licensed for treatment of epilepsy for adults and children in Canada: vagus nerve stimulation (VNS) and deep brain stimulation (DBS). Both approaches appear to be effective at reducing the frequency of seizures in adults. However, the evidence on DBS is limited to a single study with adults; we found no studies of DBS with children. Studies on VNS showed that both adults and children had fewer hospitalizations and emergency department visits after the procedure. Both procedures carry serious risks, but several longer-term studies have found that adverse events appear to be limited. The cost of VNS, including the process of assessing whether or not patients are good candidates for the procedure, is estimated to be about $40,000 per person (and higher for DBS because the device is more expensive and the operating time is longer). Of the 70,000 people in Ontario with epilepsy, about 1,400 (300 children and 1,110 adults) may be candidates for VNS to reduce their seizures.