Cost-effectiveness and threshold analysis of deep brain stimulation vs. treatment-as-usual for treatment-resistant depression.

Treatment-resistant depression (TRD) affects approximately 2.8 million people in the U.S. with estimated annual healthcare costs of $43.8 billion. Deep brain stimulation (DBS) is currently an investigational intervention for TRD. We used a decision-analytic model to compare cost-effectiveness of DBS to treatment-as-usual (TAU) for TRD. Because this therapy is not FDA approved or in common use, our goal was to establish an effectiveness threshold that trials would need to demonstrate for this therapy to be cost-effective. Remission and complication rates were determined from review of relevant studies. We used published utility scores to reflect quality of life after treatment. Medicare reimbursement rates and health economics data were used to approximate costs. We performed Monte Carlo (MC) simulations and probabilistic sensitivity analyses to estimate incremental cost-effectiveness ratios (ICER; USD/quality-adjusted life year [QALY]) at a 5-year time horizon. Cost-effectiveness was defined using willingness-to-pay (WTP) thresholds of $100,000/QALY and $50,000/QALY for moderate and definitive cost-effectiveness, respectively. We included 274 patients across 16 studies from 2009-2021 who underwent DBS for TRD and had ≥12 months follow-up in our model inputs. From a healthcare sector perspective, DBS using non-rechargeable devices (DBS-pc) would require 55% and 85% remission, while DBS using rechargeable devices (DBS-rc) would require 11% and 19% remission for moderate and definitive cost-effectiveness, respectively. From a societal perspective, DBS-pc would require 35% and 46% remission, while DBS-rc would require 8% and 10% remission for moderate and definitive cost-effectiveness, respectively. DBS-pc will unlikely be cost-effective at any time horizon without transformative improvements in battery longevity. If remission rates ≥8-19% are achieved, DBS-rc will likely be more cost-effective than TAU for TRD, with further increasing cost-effectiveness beyond 5 years.

Racial disparities in the utilization of invasive neuromodulation devices for the treatment of drug-resistant focal epilepsy.

Racial disparities affect multiple dimensions of epilepsy care including epilepsy surgery. This study aims to further explore these disparities by determining the utilization of invasive neuromodulation devices according to race and ethnicity in a multicenter study of patients living with focal drug-resistant epilepsy (DRE). We performed a post hoc analysis of the Human Epilepsy Project 2 (HEP2) data. HEP2 is a prospective study of patients living with focal DRE involving 10 sites distributed across the United States. There were no statistical differences in the racial distribution of the study population compared to the US population using census data except for patients reporting more than one race. Of 154 patients enrolled in HEP2, 55 (36%) underwent invasive neuromodulation for DRE management at some point in the course of their epilepsy. Of those, 36 (71%) were patients who identified as White. Patients were significantly less likely to have a device if they identified solely as Black/African American than if they did not (odds ratio = .21, 95% confidence interval = .05-.96, p = .03). Invasive neuromodulation for management of DRE is underutilized in the Black/African American population, indicating a new facet of racial disparities in epilepsy care.

Double dissociation of dopamine and subthalamic nucleus stimulation on effortful cost/benefit decision making.

Deep brain stimulation (DBS) and dopaminergic therapy (DA) are common interventions for Parkinson's disease (PD). Both treatments typically improve patient outcomes, and both can have adverse side effects on decision making (e.g., impulsivity).1,2 Nevertheless, they are thought to act via different mechanisms within basal ganglia circuits.3 Here, we developed and formally evaluated their dissociable predictions within a single cost/benefit effort-based decision-making task. In the same patients, we manipulated DA medication status and subthalamic nucleus (STN) DBS status within and across sessions. Using a series of descriptive and computational modeling analyses of participant choices and their dynamics, we confirm a double dissociation: DA medication asymmetrically altered participants' sensitivities to benefits vs. effort costs of alternative choices (boosting the sensitivity to benefits while simultaneously lowering sensitivity to costs); whereas STN DBS lowered the decision threshold of such choices. To our knowledge, this is the first study to show, using a common modeling framework, a dissociation of DA and DBS within the same participants. As such, this work offers a comprehensive account for how different mechanisms impact decision making, and how impulsive behavior (present in DA-treated patients with PD and DBS patients) may emerge from separate physiological mechanisms.

Cost Effectiveness of Deep Brain Stimulation for Parkinson's Disease: A Systematic Review.

BACKGROUND AND OBJECTIVE: Deep brain stimulation (DBS) is an established treatment for Parkinson's disease (PD) in patients with advanced motor symptoms with an inadequate response to pharmacotherapies. Despite its effectiveness, the cost effectiveness of DBS remains a subject of debate. This systematic review aims to update and synthesize evidence on the cost effectiveness of DBS for PD. METHODS: To identify full economic evaluations that compared the cost effectiveness of DBS with other best medical treatments, a comprehensive search was conducted of the PubMed, Embase, Scopus, and Tufts Cost-Effective Analysis registry databases. The selected papers were systematically reviewed, and the results were summarized. For the quality appraisal, we used the modified economic evaluations bias checklist. The review protocol was a priori registered with PROSPERO, CRD42022345508. RESULTS: Sixteen identified cost-utility analyses that reported 19 comparisons on the use of DBS for PD were systematically reviewed. The studies were primarily conducted in high-income countries and employed Markov models. The costs considered were direct costs: surgical expenses, calibration, pulse generator replacement, and annual drug expenses. The majority of studies used country-specific thresholds. Fourteen comparisons from 12 studies reported on the cost effectiveness of DBS compared to best medical treatments. Eleven comparisons reported DBS as cost effective based on incremental cost-utility ratio results. CONCLUSIONS: The cost effectiveness of DBS for PD varies by time horizon, costs considered, threshold utilized, and stage of PD progression. Standardizing approaches and comparing DBS with other treatments are needed for future research on effective PD management.

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.

Economic Evaluations Comparing Deep Brain Stimulation to Best Medical Therapy for Movement Disorders: A Meta-Analysis.

BACKGROUND: Movement disorders (Parkinson's disease, essential tremor, primary dystonia) are a debilitating group of conditions that are progressive in nature. The mainstay of treatment is best medical therapy; however, a number of surgical therapies are available, including deep brain stimulation. Economic evaluations are an important aspect of evidence to inform decision makers regarding funding allocated to these therapies. OBJECTIVE: This systematic review and meta-analysis evaluated the cost effectiveness of including deep brain stimulation compared with best medical therapy for movement disorder indications in the adult population. METHODS: Ovid Medical Literature Analysis and Retrieval System Online, Embase, and Cochrane Central Register of Controlled Trials were queried. Only economic evaluations reporting incremental cost-effectiveness ratios for including deep brain stimulation versus best medical therapy for movement disorders were included. Studies were reviewed in duplicate for inclusion and data abstraction. Data were harmonized using the Consumer Price Index and Purchasing Power Parity to standardize values to 2022 US dollars. For inclusion in meta-analyses, studies were required to have sufficient data available to calculate an estimate of the incremental net benefit. Meta-analyses of pooled incremental net benefit based on the time horizon were performed. The study was registered at PROSPERO (CRD42022335436). RESULTS: There were 2190 studies reviewed, with 14 economic evaluations included following a title/abstract and full-text review. Only studies considering Parkinson's disease were available for the meta-analysis. Quality of the identified studies was low, with moderate transferability to the American Healthcare System, and certainty of evidence was low. However, studies with a longer time horizon (15 years to lifetime) were found to have significant positive incremental net benefit (indicating cost effectiveness) for including deep brain stimulation with a mean difference of US$40,504.81 (95% confidence interval 2422.42-78,587.19). CONCLUSIONS: Deep brain stimulation was cost effective for Parkinson's disease when considered over the course of the patient's remaining life after implantation. TRIAL REGISTRATION: Clinical Trial Registration: PROSPERO (CRD42022335436).

Disparities in Access to Deep Brain Stimulation and Responsive Neurostimulation Approaches to Drug-Resistant Epilepsy.

BACKGROUND: Epilepsy affects 1% to 2% of the global population, and those who are resistant to medical treatment may be candidates for neuromodulation. In select populations, brain stimulation approaches including deep brain stimulation (DBS) and responsive neurostimulation (RNS) are used. Although studies have shown that patients from Black, Hispanic, lower income, and rural communities have less access to epilepsy care and have lower rates of epilepsy surgery, disparities in the use of brain stimulation for epilepsy treatment are currently not known. MATERIALS AND METHODS: We queried the US National Inpatient Sample data base from January 1, 2014 to December 31, 2019 for all patients discharged with an International Classification of Diseases (ICD) Ninth Revision or ICD Tenth Revision diagnosis of drug-resistant epilepsy. Among these patients discharged, the rates of brain stimulation treatment, including DBS and RNS, were reported in each subgroup of race, ethnicity, and insurance. To generate national estimates, all analyses were weighted. RESULTS: A total of 237,895 patients discharged with drug-resistant epilepsy were identified, of whom 4,925 (2.1%) received brain stimulation treatment for drug-resistant epilepsy. Black patients (n = 420, 0.9%, odds ratio [OR] = 0.51, 95% CI [0.40, 0.64]) were less likely to receive brain stimulation treatment than were White patients (n = 3300, 2.4%). There was no significant difference between Asian (n = 105, 2.3%, OR = 0.80, 95% CI [0.53, 1.33]) and Hispanic (n = 655, 2.6%, OR = 0.95, 95% CI [0.77, 1.17]) patients and White patients. No significant difference was observed between female (n = 2515, 2.1%, OR = 1.02, 95% CI [0.89, 1.17]) and male (n = 2410, 2.0%) patients either. Patients with Medicare (n = 1150, 1.2%, OR = 0.69, 95% CI [0.57, 0.84]) or Medicaid (n = 1150, 1.8%, OR = 0.52, 95% CI [0.44, 0.62]) were less likely to receive brain stimulation treatment than were those with private insurance as the primary payer (n = 2370, 3.9%). CONCLUSIONS: We discovered significant disparities in the use of brain stimulation treatments for drug-resistant epilepsy based on race and insurance status. More research will be required to determine the cause of these disparities.

Temporally non-regular patterns of deep brain stimulation (DBS) enhance assessment of evoked potentials while maintaining motor symptom management in Parkinson's disease (PD).

BACKGROUND: Traditional deep brain stimulation (DBS) at fixed regular frequencies (>100 Hz) is effective in treating motor symptoms of Parkinson's disease (PD). Temporally non-regular patterns of DBS are a new parameter space that may help increase efficacy and efficiency. OBJECTIVE: To compare the effects of temporally non-regular patterns of DBS to traditional regularly-spaced pulses. METHODS: We simultaneously recorded local field potentials (LFP) and monitored motor symptoms (tremor and bradykinesia) in persons with PD during DBS in subthalamic nucleus (STN). We quantified both oscillatory activity and DBS local evoked potentials (DLEPs) from the LFP. RESULTS: Temporally non-regular patterns were as effective as traditional pulse patterns in modulating motor symptoms, oscillatory activity, and DLEPs. Moreover, one of our novel patterns enabled recording of longer duration DLEPs during clinically effective stimulation. CONCLUSIONS: Stimulation gaps of 50 ms can be used to increase efficiency and to enable regular assessment of long-duration DLEPs while maintaining effective symptom management. This may be a promising paradigm for closed-loop DBS with biomarker assessment during the gaps.

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.

Interplay between speech and gait variables in Parkinson's disease patients treated with subthalamic nucleus deep brain stimulation: A long-term instrumental assessment.

OBJECTIVE: To evaluate correlations between speech and gait parameters in the long term and under different medication and subthalamic nucleus deep brain stimulation (STN-DBS) conditions in a cohort of advanced Parkinson's disease (PD) patients. METHODS: This observational study included consecutive PD patients treated with bilateral STN-DBS. Axial symptoms were evaluated using a standardized clinical-instrumental approach. Speech and gait were assessed by perceptual and acoustic analyses and by the instrumented Timed Up and Go (iTUG) test, respectively. Disease motor severity was evaluated with the total score and subscores of the Unified Parkinson's Disease Rating Scale (UPDRS) Part III. Different stimulation and drug treatment conditions were assessed: on-stimulation/off-medication, off-stimulation/off-medication, and on-stimulation/on-medication. RESULTS: Twenty-five PD patients with a 5-year median follow-up after surgery (range 3-7 years) were included (18 males; disease duration at surgery: 10.44 [SD 4.62] years; age at surgery: 58.40 [SD 5.73] years). In the off-stimulation/off-medication and on-stimulation/on-medication conditions, patients who spoke louder had also the greater acceleration of the trunk during gait; whereas in the on-stimulation/on-medication condition only, patients with the poorer voice quality were also the worst to perform the sit to stand and gait phases of the iTUG. Conversely, patients with the higher speech rate performed well in the turning and walking phases of the iTUG. CONCLUSIONS: This study underlines the presence of different correlations between treatment effects of speech and gait parameters in PD patients treated with bilateral STN-DBS. This may allow us to better understand the common pathophysiological basis of these alterations and to develop a more specific and tailored rehabilitation approach for axial signs after surgery.

Deep Brain Stimulation for Advanced Parkinson Disease in Developing Countries: A Cost-Effectiveness Study From China.

BACKGROUND: The cost-effectiveness of deep brain stimulation (DBS) is more favorable than best medical treatment (BMT) for advanced Parkinson disease (PD) in developed countries. However, it remains unclear in developing countries, where the cost of DBS may not be reimbursed by health care system. OBJECTIVE: To model and evaluate the long-term cost-effectiveness of DBS for advanced PD in China from a patient payer perspective. METHODS: We developed a Markov model representing the clinical progress of PD to predict the disease progression and related medical costs in a 15-year time horizon. The incremental cost-effectiveness ratio (ICER) and net benefit were used to evaluate the cost-effectiveness of DBS vs BMT. RESULTS: DBS treatment led to discounted total costs of ¥370 768 ($56 515.20) (95% CI, ¥369 621.53-371 914.88), compared with ¥48 808 ($7439.68) (95% CI, ¥48 502.63-49 114.21) for BMT, with an additional 1.51 quality-adjusted life years gained, resulting in an ICER of ¥213 544 ($32 549.96)/quality-adjusted life years (95% CI, ¥208 177.35-218 910.10). Sensitivity analysis showed that DBS-related cost has the most substantial impact on ICER. Nation-wide net benefit of BMT and DBS were ¥33 819 ($5154.94) (95% CI, ¥30 211.24-37 426) and ¥30 361 ($4627.85) (95% CI, ¥25 587.03-39 433.66), respectively. Patient demographic analysis showed that more favorable DBS cost-effectiveness was associated with younger age and less severe disease stage. CONCLUSION: DBS is cost-effective for patients with advanced PD over a 15-year time horizon in China. However, compared with developed countries, DBS remains a substantial economic burden for patients when no reimbursement is provided. Our findings may help inform cost-effectiveness-based decision making for clinical care of PD in developing countries.

Comparison of utilization and cost of healthcare services and pharmacotherapy following implantation of vagus nerve stimulation vs. responsive neurostimulation or deep brain stimulation for the treatment of drug-resistant epilepsy: analyses of a large United States healthcare claims database.

AIM: Vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS) all are options for drug-resistant epilepsy (DRE). However, little is known about how the choice of neurostimulation impacts subsequent healthcare costs. MATERIALS AND METHODS: We used a large US healthcare claims database to identify all patients with epilepsy who underwent neurostimulation between 2012 and 2019. Eligible patients were identified and stratified based on procedure received (VNS vs. RNS/DBS). VNS patients were matched by propensity scoring to RNS/DBS patients. Use and cost of healthcare resources and pharmacotherapy were ascertained over the 24-month period following neurostimulation, incorporating all-cause and epilepsy-related measures. Disease-related care was defined based on diagnoses of claims for medical care and relevant pharmacotherapies. RESULTS: Seven hundred and ninety-two patients met all selection criteria. VNS patients were younger, were prescribed a higher pre-index mean number of anti-seizure medications (ASMs), and had higher pre-index levels of use and cost of epilepsy-related healthcare services. We propensity matched 148 VNS patients to an equal number of RNS/DBS patients. One year following index date (inclusive), mean total all-cause healthcare costs were 50% lower among VNS patients than RNS/DBS patients, and mean epilepsy-related costs were 55% lower; corresponding decreases at the two-year mark were 41% and 48%, respectively. LIMITATIONS: Some clinical variables, such as seizure frequency and severity, quality of life, and functional status were unavailable in the database, precluding our ability to comprehensively assess differences between devices. Administrative claims data are subject to billing code errors, inaccuracies, and missing data, resulting in possible misclassification and/or unmeasured confounding. CONCLUSIONS: After matching, VNS was associated with significantly lower all-cause and epilepsy-related costs for the two-year period following implantation. All-cause and epilepsy-related costs remained statistically significantly lower for VNS even after costs of implantation were excluded.

For some people with epilepsy, medications do not work very well. For these people, other treatment options exist. One such treatment is neurostimulation. There are three types of neurostimulators­vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS). All three devices are known to reduce seizures in patients who have tried several medications. However, it is not known how these devices impact the costs of care. We compared the use and costs of medical care over 2 years between patients who got VNS and those who got RNS/DBS. Before comparing the groups, we made sure that they were balanced. Patients who got VNS were less likely than patients who got RNS/DBS to go to the hospital during the follow-up period. Patients who got VNS also had lower healthcare costs than patients who got RNS/DBS during follow-up. These differences were seen for all medical care costs. These differences also were seen in the costs of care for epilepsy. Our results suggest that the use of VNS is associated with fewer hospitalizations than RNS/DBS, and also that use of VNS is associated with lower healthcare costs than RNS/DBS.

Potential clinical and economic benefits of remote deep brain stimulation programming.

Deep brain stimulation (DBS) teleprogramming may help reducing travel-related and other financial burdens for patients and maintaining DBS care in special situations. To determine travel-related burdens of DBS patients and explore effects of COVID-19 on DBS care. Travel- and visit-related data of 319 patients were retrospectively analyzed for the first year, five years, and ten years after initiating DBS. Frequencies of in-person and telemedicine visits over the 18-month periods just before and after the outbreak of COVID-19 in Hungary were also compared. Average travel distance during an in-person visit was 415.2 ± 261.5 km, while average travel time was 342.1 ± 199.4 min. Travel costs for the first year, five years, and ten years were 151.8 ± 108.7, 461.4 ± 374.6, and 922.7 ± 749.1 Euros, respectively. Travel distance, age, and type and severity of disease could help identify patients who would particularly benefit from teleprogramming. We detected a significant decrease in the number of visits during COVID-19 pandemic (from 3.7 ± 2.1 to 2.4 ± 2.7; p < 0.001) which mainly resulted from the decreased frequency of in-person visits (3.6 ± 2.0 vs. 1.7 ± 1.8; p < 0.001). Our results support the introduction of DBS teleprogramming in Hungary which could save money and time for patients while maintaining a secure delivery of DBS.

The cost-effectiveness of unilateral magnetic resonance-guided focused ultrasound in comparison with unilateral deep brain stimulation for the treatment of medically refractory essential tremor in England.

OBJECTIVES: This study aims to ascertain the cost-effectiveness of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of medically refractory Essential Tremor (mrET) in England. Essential Tremor (ET) is the most common movement disorder affecting approximately 1 million in the UK causing considerable societal impact affecting patients, carers and the wider healthservice. Medical treatment has mixed efficacy, with approximately 25-55% of ET medication refractory. Deep brain stimulation (DBS) is a proven neurosurgical treatment; however, the risks of surgery and anaesthesia mean some patients are ineligible. MRgFUS is an emerging noninvasive technique that causes tremor suppression by thermal ablation of tremor-sensitive brain tissue. Several international clinical trials have demonstrated MRgFUS is safe and clinically effective; however, to-date no cost-effectiveness study has been performed in Europe. METHODS: A Markov model was used to assess two subpopulations of mrET - those eligible and those ineligible for neurosurgery - in the context specific to England and its healthcare system. For those eligible for neurosurgery, MRgFUS was compared to DBS, the current standard treatment. For those ineligible for neurosurgery, MRgFUS was compared to treatment with medication alone. The model calculated the Incremental cost-effectiveness ratio (ICER) with appropriate sensitivity and scenario analyses. RESULTS: For those eligible for neurosurgery: In the model base case, the MRgFUS was economically dominant compared to DBS; MRgFUS was less costly (£19,779 vs £62,348) and more effective generating 0.03 additional quality-adjusted life-years (QALYs) per patient (3.71 vs 3.68) over the 5-year time horizon.For those ineligible for neurosurgery: In the model base case, MRgFUS cost over £16,000 per patient more than medication alone (£19,779 vs £62,348) but yielded 0.77 additional QALYs per patient(3.71 vs 2.95), producing an incremental cost-effectiveness ratio (ICER) of £20,851 per QALY. This ICER of £20,851 per QALY falls within the National Institute for Clinical Excellence's (NICE) willingness to pay threshold (WTP) of 20,000-30,000 demonstrating the cost-effectiveness profile of MRgFUS. CONCLUSION: This study demonstrates the favourable cost-effectiveness profile of MRgFUS for the treatment of mrET in England; in both patients suitable and not suitable for neurosurgery. ADVANCES IN KNOWLEDGE: The introduction of MRgFUS as a widely available ET treatment in UK is currently undergoing the necessary stages of regulatory approval. As the first European study, these favourable cost-effectiveness outcomes (notably the model base case ICER falling within NICE's WTP) can provide a basis for future commissioning of brain MRgFUS treatments in the UK, Europe and globally.

Estimulação cerebral profunda para o tratamento da distonia primária generalizada e distonia cervical / Deep brain stimulation for the treatment of primary generalized dystonia and cervical dystonia

INTRODUÇÃO: A distonia é um distúrbio neurológico caracterizado por contrações musculares involuntárias, responsáveis por posturas e movimentos anormais. Sua expressão clínica é determinada pela gravidade e distribuição dos músculos envolvidos, desde variações focais e segmentares mais leves, a casos mais graves de manifestação generalizada. No Brasil, no âmbito do Sistema Único de Saúde (SUS), há um Protocolo Clínico e Diretrizes Terapêuticas sobre o cuidado de Distonia e Espasmo Hemifacial que preconiza a utilização da Toxina Botulínica Tipo A (TBA). A estimulação cerebral profunda (Deep Brain Stimulation - DBS) é um procedimento cirúrgico utilizado no tratamento de várias doenças neurológicas, normalmente em casos refratários à terapia usual. A DBS consiste na implantação de um dispositivo médico para fornecer estimulação elétrica a regiões específicas do cérebro. Tendo em vista que existem produtos de saúde aprovados pela Anvisa para realização da DBS e que o procedimento já está disponível no SUS para determinadas condições, o presente relatório foi desenvolvido com o objetivo de compreender a viabilidade de ampliação de uso desse procedimento no SUS para o tratamento de distonia primária generalizada e distonia cervical. PERGUNTA DE PESQUISA: O uso da DBS é eficaz, seguro e custo-efetivo para o tratamento de distonia primária generalizada e distonia cervical em pacientes adultos e pediátricos refratários ao tratamento convencional? EVIDÊNCIAS CLÍNICAS: Foi realizada uma revisão sistemática a partir de buscas nas bases de dados MEDLINE (via Pubmed), EMBASE, Cochrane Library, LILACS, IBECS, BRISA (via BVS), considerando o tratamento de distonia primária generalizada e distonia cervical com o procedimento de estimulação cerebral profunda. Foram estabelecidos critérios de elegibilidade abrangentes devido à escassez de estudos disponíveis na literatura científica. Os estudos foram avaliados quanto ao risco de viés com a ferramenta Cochrane Risk of Bias Tool ­ ROB 2.0 para Ensaio Clínico Randomizado (ECR) e a ferramenta Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) para os estudos observacionais. A qualidade geral da evidência foi avaliada utilizando a abordagem GRADE (Grading of Recommendatons Assessment, Development and Evaluaton). Para distonia primária generalizada, foram incluídos 17 estudos que envolveram 350 pacientes, entre crianças e adultos. Entre os estudos identificados um era ensaio clínico randomizado (ECR) que comparou DBS e sham; os demais estudos eram ensaios clínicos não randomizados (n=4) ou observacionais (estudos de coorte (n=10) e séries de casos (n=2). O ECR analisado incluiu tanto crianças quanto adultos e avaliou no total 40 pacientes. Os resultados apresentados foram positivos na redução do comprometimento motor (redução de 39,3%) e da incapacidade (redução de 37,5%) em pacientes que realizaram a DBS, avaliados pela escala Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). é importante destacar a consistência em relação aos resultados sempre mostrarem benefício e a magnitude do efeito, que é relevante clinicamente. Os estudos observacionais incluídos também sugerem resultados positivos com o uso da DBS, com qualidade geral da evidência variando de baixa a muito baixa devido ao risco de viés grave ou crítico, principalmente pela presença de potenciais fatores de confundimento e/ou problemas relacionados ao cegamento (ausência de descrição ou relato inadequado). Para distonia cervical, foram incluídos 13 estudos que envolveram 300 pacientes, a maioria dos estudos incluindo apenas adultos. Entre os estudos identificados um era ECR comparando a DBS com procedimento sham; os demais estudos clínicos eram não randomizados (n=2) ou observacionais (estudos de coorte (n=9) e caso-controle (n=1). O ECR avaliou 62 pacientes adultos e os resultados, avaliados pela escala Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), indicam que a DBS reduz o comprometimento motor (redução média de 5,1 pontos), incapacidade (redução média de 5,6 pontos) e dor (redução média de 4,4 pontos) em pacientes com distonia cervical refratária ao tratamento farmacológico quando comparado com a estimulação simulada. Novamente é importante ressaltar que os resultados foram clinicamente relevantes e observou-se consistência entre os achados no ECR e nos demais estudos. Os estudos observacionais incluídos também relatam resultados positivos com o uso da DBS. AVALIAÇÃO ECONÔMICA: A razão de custo-efetividade incremental da ampliação de uso da DBS foi de R$ 4.378,58 por QALY na distonia generalizada e de R$46.119,11 por QALY na distonia cervical, com a maior parte dos resultados demonstrando superioridade clínica da tecnologia avaliada na análise de sensibilidade. Pela análise de sensibilidade probabilística, 95% dos valores de RCEI estão abaixo de R$7.000 para a distonia generalizada e abaixo de R$1.000.000,00 para a cervical. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: Estima-se que 945 pessoas possuem distonia generalizada e 10.698 distonias cervical no Brasil e que 482 pacientes sejam passíveis de serem tratados com DBS em 2022. Considerando a participação de mercado do procedimento, 72 pacientes fariam a DBS em 2022, 124 em 2023, 131 em 2024, 98 em 2025 e 55 em 2026. Isso corresponde, em uma ampliação de uso progressiva, um impacto orçamentário de, aproximadamente, R$7.710.181,32 em 5 anos. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: No Monitoramento do Horizonte Tecnológico foram encontradas 2 novas tecnologias com registros ANVISA e FDA (Percept PC Brain Sense e Vercise Genus). Em relação aos depósitos e patentes concedidas foi possível evidenciar 1 documento patentário, com depósito em 2021, referente a métodos e sistemas para estimulação cerebral profunda focalizada não invasiva. CONSIDERAÇÕES FINAIS: As evidências disponíveis para a comparação entre DBS e estimulação simulada para os tipos de distonia avaliadas foram baseadas apenas em dois ECRs. Os resultados dos ECRs mostraram resultados favoráveis à intervenção. Os estudos observacionais identificados, ainda que apresentem limitações metodológicas, também apoiam os resultados dos ECRs avaliados. Como o cuidado da distonia em casos refratários ao tratamento usual carece de alternativas terapêuticas é possível que os pacientes com distonia já façam uso desse procedimento por meio dos CIDs do grupo R (R250, R251, R252, R253 e R258), para os quais o procedimento já está disponível no SUS. RECOMENDAÇÃO PRELIMINAR: os membros presentes no Plenário da Conitec, em sua 110ª Reunião Ordinária, realizada no dia 06 de julho de 2022, deliberaram que a matéria fosse disponibilizada em consulta pública com recomendação preliminar favorável à ampliação de uso da estimulação cerebral profunda para o tratamento da distonia. Para essa recomendação, a Conitec considerou que as evidências acerca da eficácia e segurança do procedimento são escassas, mas provém de ensaios clínicos randomizados com resultados clinicamente relevantes, o quadro clínico que exige seu uso seria para aqueles pacientes refratários a todos os demais tratamentos. CONSULTA PÚBLICA: Todos os participantes da CP nº 50/2022, que realizaram contribuições frente ao tema avaliado, realizada entre os dias 01/08/2022 e 22/08/2022, concordaram com recomendação preliminar da Conitec favorável à ampliação de uso da estimulação cerebral profunda para o tratamento da distonia primária generalizada e distonia cervical. Foram recebidas 23 contribuições, sendo 13 através do formulário técnico-científico e 10 através do formulário de experiência ou opinião. De forma geral, as contribuições ressaltaram os benefícios clínicos do procedimento, principalmente destacando melhora da qualidade de vida. Também comentaram a respeito do alto custo e dificuldade de acesso ao procedimento. RECOMENDAÇÃO FINAL DA CONITEC: Pelo exposto, o Plenário da Conitec, em sua 112ª Reunião Ordinária, realizada no dia 31 de agosto de 2022, deliberou por unanimidade recomendar a ampliação de uso da estimulação cerebral profunda para o tratamento da distonia primária generalizada e distonia cervical em pacientes refratários a terapia convencional. Os membros da Conitec consideraram os benefícios proporcionados pelo procedimento e a necessidade de uso para aqueles pacientes refratários aos demais tratamentos. A consulta pública não trouxe elementos para mudança da recomendação preliminar. Por fim, foi assinado o Registro de Deliberação nº 767/2022. DECISÃO: de ampliar o uso, no âmbito do Sistema Único de Saúde - SUS, da estimulação cerebral profunda para o tratamento de distonias, conforme protocolo estabelecido pelo Ministério da Saúde, conforme a Portaria nº 108, publicada no Diário Oficial da União nº 192, seção 1, página 61, em 7 de outubro de 2022.

A non-contact system for intraoperative quantitative assessment of bradykinesia in deep brain stimulation surgery.

BACKGROUND AND OBJECTIVE: Deep brain stimulation (DBS) is an effective treatment for a number of neurological diseases, especially for the advanced stage of Parkinson's disease (PD). Objective assessment of patients' motor symptoms is crucial for accurate electrode targeting and treatment. Existing approaches suffer from subjective variability or interference with voluntary motion. This work is aimed to establish an objective assessment system to quantify bradykinesia in DBS surgery. METHODS: Based on the analysis of the requirements for intraoperative assessment, we developed a system with non-contact measurement, online movement feature extraction, and interactive data analysis and visualization. An optical sensor, Leap Motion Controller (LMC), was taken to detect hand movement in three clinical tasks. A graphic user interface was designed to process, compare and visualize the collected data and assessment results online. Quantified movement features include amplitude, frequency, velocity, their decrement and variability, etc. Technical validation of the system was performed with a motion capture system (Mocap), with respect to data-level and feature-level accuracy and reliability. Clinical validation was conducted with 20 PD patients for intraoperative assessments in DBS surgery. Treatment responses with respect to the bradykinesia movement features were analyzed. Single case analysis and group statistical analysis were performed to examine the differences between preoperative and intraoperative performance, and the correlation between the clinical ratings and the quantified assessment was analyzed. RESULTS: For the movements measured by LMC and Mocap, the average Pearson's correlation coefficient was 0.986, and the mean amplitude difference was 2.11 mm. No significant difference was found for all movement features quantified by LMC and Mocap. For the clinical tests, key movement features showed significant differences between the preoperative baseline and intraoperative performance when the brain stimulation was ON. The assessment results were significantly correlated with the MDS-UPDRS clinical ratings. CONCLUSIONS: The proposed non-contact system has established itself as an objective intraoperative assessment, analysis, and visualization tool for DBS treatment of Parkinson's disease.

Intraoperative cone-beam CT with metal artifact reduction for assessment of the electrode position and the intracranial structures during deep brain stimulation procedure.

BACKGROUND: In deep brain stimulation (DBS) for Parkinson's disease (PD), the clinical outcome largely depends on the appropriate position of the electrode implanted in the targeted structure. In intraoperative cone-beam computed tomography (CT) performed for the evaluation of the electrode position, the metal artifact induced by the implanted electrode can prevent the precise localization of the electrode. Metal artifact reduction (MAR) techniques have been recently developed that can dramatically improve the visualization of objects by reducing metal artifacts after performing cone-beam CT. Hence, in this case series, we attempted to clarify the usefulness and accuracy of intraoperative cone-beam CT with MAR (intraCBCTwM) by comparing with both intraoperative cone-beam CT without MAR (intraCBCTwoM) and conventional postoperative CT (post-CT) for the assessment of the implanted electrode position and the intracranial structures during DBS procedures. METHODS: Between November 2019 and December 2020, 10 patients with PD who underwent DBS at our institution were recruited, and the images of 9 patients (bilateral: n = 8, unilateral: n = 1) were analyzed. The artifact index (AI) in intraCBCTwM or intraCBCTwoM, and conventional post-CT were retrospectively assessed using the standard deviation of the region-of-interest around the implanted electrodes and background noise. Additionally, the Euclidean distances gap of electrode tip based on post-CT in each fusion image was compared between intraCBCTwM and intraCBCTwoM. RESULTS: The AI was significantly lower in intraCBCTwM than in intraCBCTwoM (P < 0.01). The mean Euclidean distance between the tip of the electrode in intraCBCTwM and in post-CT was significantly shorter compared to that in intraCBCTwoM (P < 0.05). CONCLUSIONS: The results reported here suggest that intraCBCTwM is a more useful and accurate method than intraCBCTwoM to assess the implanted electrode position and intracranial structures during DBS.

Cross-Sectional Analysis of US Health Insurance Payer Policies for Humanitarian Device Exemption Indications for Deep Brain Stimulation.

BACKGROUND: The US Food and Drug Administration (FDA) has granted deep brain stimulation (DBS) approval under the humanitarian device exemption (HDE) pathway for both dystonia and obsessive-compulsive disorder (OCD). However, recent reports from the community of functional neurosurgeons suggest that insurance authorization remains a disproportionate barrier to OCD DBS implantation despite both conditions having similar support from the FDA. This cross-sectional study of health insurance policies quantifies the current payer landscape for these two interventions. OBJECTIVES: The aim of this study was to quantify the current payer policy coverage of DBS under HDE status for OCD as compared to DBS for dystonia for eligible patients in the US insurance market. METHODS: A commercial health insurance policy database was queried for documentation on DBS for dystonia and OCD. Results were individually analyzed for payer policy coverage statements on DBS for either dystonia or OCD and categorized as unique or nonunique policies. Unique policy positions were then coded for the geographic region, whether coverage was offered, and guidelines cited as evidence and justification. RESULTS: From the 80 policies in the database, there were 34 unique policies addressing DBS for either dystonia or OCD representing coverage of all 50 states. Of the 34 unique policies, 3 (9%) covered DBS for OCD, while 32 (94%) covered dystonia. Only 2 policies covered neither intervention. CONCLUSIONS: In spite of similar levels of support from the FDA, DBS for OCD has less support from insurance companies on a national level. This study begins to quantify the disparity noted by functional neurosurgeons in recent literature.

The Deep Brain Stimulation Impairment Scale: A useful complement in assessment of well-being and functioning in DBS-patients - Results from a large multicentre survey in patients with Parkinson's disease.

BACKGROUND: Deep Brain Stimulation (DBS) has been proven to alleviate motor symptoms in Parkinson's Disease (PD). Regarding non-motor symptoms, however, inconsistencies have been reported, on whether DBS causes reductions in well-being and functioning. To assess motor and non-motor impairment in DBS-patients, the Deep Brain Stimulation Impairment Scale (DBS-IS) has been developed. Yet, the extent to which the DBS-IS detects impairment in DBS-patients and thus could serve as a useful tool that complements the PDQ-39 (gold standard) in assessment of well-being and functioning in PD-patients has not been shown. OBJECTIVES: By comparing DBS and non-DBS-patients we aimed to identify DBS-specific symptoms. We thereby aimed to show in how far the DBS-IS complements the PDQ-39 in assessing well-being and functioning in PD patients under DBS. METHODS: In a cross-sectional study, 186 DBS-patients were matched (for age, disease duration and sex) to 186 non-DBS-patients (N = 372) and the two groups were compared regarding well-being and functioning: Impairment was assessed via DBS-IS and overall Quality of Life (QoL) was assessed via PDQ-39. Additionally, we analyzed differences in impairment between age and disease duration clusters. RESULTS: DBS-patients showed significantly higher total impairment (DBS-IS) and significantly higher impairment on the subscales Postural Instability and Gait difficulties and speaking difficulties than non-DBS-patients. Impairment increased with age and disease duration and, overall, differences in impairment rose by age. Overall QoL (PDQ-39) was non-significantly lower in DBS-patients. CONCLUSION: Since there is evidence that the PDQ-39 misses some DBS-specific symptoms, the DBS-IS is recommended to complement the PDQ-39 when assessing DBS-patients.