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Deep Brain Stimulation: A Principled and Pragmatic Approach to Understanding the Ethical and Clinical Challenges of an Evolving Technology
Abstract
DBS has emerged in the past few decades as a powerful clinical tool in the treatment of movement disorders
such as dystonia
and Parkinson’s disease
. As a result of its striking effects, the therapeutic utility of DBS has been investigated in a number of different neurological and neuropsychiatric conditions. Ethical discussion has accompanied this evolution of DBS and has led to the identification of a number of important ethical challenges. In this chapter, we review these challenges based on three of the key principles of biomedical ethics
(autonomy
, justice
, and non-maleficence
). Specifically, we adopt a pragmatic perspective by reviewing the ethical issues as they emerge within the context of Parkinson’s disease, as this can serve to guide further ethical thinking on the future of DBS. Through this contextualization, we enrich the meaning of the Ethical principle
s and increase their specificity. We hope that this contribution will inform readers and also stimulate discussion related to areas where important questions remain unanswered and where further research would need to be undertaken to understand and enact ethical principles.
... 37 One notable risk associated with chronic electric stimulation of the brain, although also associated with other forms of neurosurgical intervention, broadly involves the potential for psychological effects or impacts on personal identity. 9,20,38,39 As a result, the ethical question of whether and to what degree patients should be informed about the potential for psychological and identity effects must also be addressed, even though limited empirical data on these effects exist, with even fewer data on whether patients perceive these effects subjectively as good or bad. 9,40 As a general principle, to better assess the risk-to-benefit ratio for patients undergoing innovative surgical procedures, data should be supplied for local outcomes compared with national ones. ...
: Deep brain stimulation (DBS) for psychiatric disorders needs to be investigated in proper research trials. However, there are rare circumstances in which DBS could be offered to psychiatric patients as a form of surgical innovation, therefore potentially blurring the lines between these research trials and health care. In this article, we discuss the conditions under which surgical innovation may be accepted as a practice falling at the frontiers of standard clinical care and research per se. However, recognizing this distinction does not settle all ethical issues. Our article offers ethical guideposts to allow clinicians, surgical teams, institutions, and international review boards to deliberate about some of the fundamental issues that should be considered before surgical innovation with psychiatric DBS is undertaken. We provide key guiding questions to sustain this deliberation. Then we review the normative and empirical literature that exists to guide reflection about the ethics of surgical innovation and psychiatric DBS with respect to general ethical questions pertinent to psychiatric DBS, multidisciplinary team perspectives in psychiatric DBS, mechanisms for oversight in psychiatric DBS, and capacity and consent in psychiatric DBS. The considerations presented here are to recognize the very specific nature of surgical innovation and to ensure that surgical innovation in the context of psychiatric DBS remains a limited, special category of activity that does not replace appropriate surgical research or become the standard of care based on limited evidence. ABBREVIATIONS: DBS, deep brain stimulation IRB, institutional review board OCD, obsessive-compulsive disorder Copyright (C) by the Congress of Neurological Surgeons
... That is, how to maintain a supply of human brains? If all the bodies are gone, where do the ova and sperm come (Monaghan and Maden, 2013;Racine et al., 2014). In that case, human reproduction can take place in a biological fashion, without baby factories, thus maintaining the supply of human brains. ...
Ray Kurzweil predicts that artificial intelligence will equal and then surpass human intelligence in the not-too-distant future, in what he calls the “moment of singularity.” Advances in brain/machine interfacing (BMI) may be viewed as a challenge to this futuristic prediction. BMIs strive to instrument human brains with unlimited memory, calculation, and communication abilities, which provide a competitive edge to human brain power versus artificial intelligence. This paper makes a case for a hybrid human/robot that merges the brain function with artificial intelligence components, and prevents the “moment of singularity” from ever occurring.
This study is framed within the objectives of Clinical Ontology, namely, the formulation of true, coherent and accessible discourses in order to help patients manage unavoidable and destructive experiences about the nature of being, becoming, and its limits. First, I analyze four different inauthentic experiences (IE), which are deeply associated with neuro-technological development, and from which are emerging a new and growing vulnerable group of patients. Second, I propose two basis conditions for a successful ontological treatment: (a) the patient should value the unpleasant feelings of IE negatively; and (b) the patient should believe that a better understanding of reality (or at least, of his or her own life) provides a means to neutralize and replace unpleasant feelings with others that are more enjoyable and fulfilling. Finally, I defend that therapeutic technologies are not the only triggers of IE, hence they should not be the only target of investigation of this field.
Chronic illness is perceived as a particular kind of event. The aim of this paper is to
understand the personal, familial and professional difficulties experienced by patients in
France who have a neurodegenerative disease and undergo cerebral implants. This paper is
based on the assumption that a treatment using biotechnical techniques is a unique
disruptive experience which redefines the patient’s life. Thirty patients (13 women and 17
men) from two French hospitals were interviewed at different stages of their medical
history. Despite the excellent overall outcome of neurosurgery in patients with Parkinson’s
disease, there is often a contrast between the improvement in motor disability and the
patient’s difficulty in returning to normal life. These results allow us to analyse the link
between the neurosciences and the experience of chronic illness.
Deep brain stimulation (DBS) is an effective surgical treatment for medication-refractory hypokinetic and hyperkinetic movement disorders, and it is being explored for a variety of other neurological and psychiatric diseases. Deep brain stimulation has been Food and Drug Administration-approved for essential tremor and Parkinson disease and has a humanitarian device exemption for dystonia and obsessive-compulsive disorder. Neurostimulation is the fruit of decades of both technical and scientific advances in the field of basic neuroscience and functional neurosurgery. Despite the clinical success of DBS, the therapeutic mechanism of DBS remains under debate. Our objective is to provide a comprehensive review of DBS focusing on movement disorders, including the historical evolution of the technique, applications and outcomes with an overview of the most pertinent literature, current views on mechanisms of stimulation, and description of hardware and programming techniques. We conclude with a discussion of future developments in neurostimulation.
Deep brain stimulation (DBS) is an approved neurosurgical intervention for motor disorders such as Parkinson disease. The emergence of psychiatric uses for DBS combined with the fact that it is an invasive and expensive procedure creates important ethical and social challenges in the delivery of care that need further examination. We endeavored to examine health care provider perspectives on ethical and social challenges encountered in DBS.
Health care providers working in Canadian DBS surgery programs participated in a semistructured interview to identify and characterize ethical and social challenges of DBS. A content analysis of the interviews was conducted.
Several key ethical issues, such as patient screening and resource allocation, were identified by members of neurosurgical teams. Providers described challenges in selecting patients for DBS on the basis of unclear evidence-based guidance regarding behavioral issues or cognitive criteria. Varied contexts of resource allocation, including some very challenging schemas, were also reported. In addition, the management of patients in the community was highlighted as a source of ethical and clinical complexity, given the need for coordinated long-term care.
This study provides insights into the complexity of ethical challenges that providers face in the use of DBS across different neurosurgical centers. We propose actions for health care providers for the long-term care and postoperative monitoring of patients with DBS. More data on patient perspectives in DBS would complement the understanding of key challenges, as well as contribute to best practices, for patient selection, management, and resource allocation.
Background. Although the clinical effectiveness of deep brain stimulation (DBS) in Parkinson's disease is established, there has been less examination of its social aspects.
Methods and Results. Building on qualitative comments provided by healthcare providers, we present four different social and relational issues (need for social support, changes in relationships (with self and partner) and challenges with regards to occupation and the social system). We review the literature from multiple disciplines on each issue. We comment on their ethical implications and conclude by establishing the future prospects for research with the possible expansion of DBS for psychiatric indications.
Conclusions. Our review demonstrates that there are varied social issues involved in DBS. These issues may have significant impacts on the perceived outcome of DBS by patients. Moreover, the fact that the social impact of DBS is still not well understood in emerging psychiatric indications presents an important area for future examination.
In this article we report relevant data that shed light on the topic of hope and patients' expectations in the use of DBS, for standard, approved, and established indications, based on a broader qualitative study on the ethical and social challenges that healthcare providers face in the field of DBS.
International and national consensus guidelines define appropriate indications for implantable cardioverter-defibrillators (ICDs), but the variability in implant rates in 'real world' clinical practice is still unknown.
In Emilia-Romagna, an Italian region with around 4.3 million inhabitants, a web-based registry was instituted to collect data for all ICDs implanted. Between January 2006 and December 2008, data from all consecutive patients resident in this region who underwent first implant of an ICD or a biventricular ICD were collected and standardized, considering each regional area (i.e. each of the nine provinces). The overall number of implanted ICDs had an increase in years 2007 and 2008, with a relative increase in comparison to 2006, by 14 and 48% respectively, reaching an average value of 16.2 per 10,000 inhabitants in 2008. Most of the increase was due to a rise in ICDs for primary prevention. The ratio between the implant rates of the provinces with the highest and the lowest implant rates, respectively, was around 2 in 2008.
Implant rates for ICDs, considering both primary and secondary prevention of sudden death, show up to two-fold variations even in a geographical region where the general level of health care is advanced and well appreciated by the population. The lack of a common strategy for sudden death prevention, approved by both physicians and institutional regional authorities, together with some degree of variability in translating guidelines into clinical practice, were identified as the main factors explaining the heterogeneity in ICD implant rates.
To find predictors of cognitive decline and quality of life 1 year after bilateral subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson's disease (PD).
A total of 105 patients were evaluated with a comprehensive neuropsychological assessment before and 12 months after surgery. A control group of 40 PD patients was included to control for effects of repeated testing and disease progression. The authors determined individual changes in cognition, mood and quality of life using a statistical method that controls for multiple comparisons, and performed logistic regression analyses to assess predictors of cognitive changes and quality of life.
12 months after surgery, the improvement in motor function was 41% (Unified Parkinson's Disease Rating Scale Part 3 score in off). The STN group showed a large improvement in quality of life compared with the control group (Cohen d=0.9). At the individual level, 32% (95% CI 22 to 40) of the STN group showed a substantial improvement in quality of life. 36% (95% CI 27 to 46) of the STN patients showed a profile of cognitive decline compared with the control group. Mood improved in 16 STN patients and declined in 16 subjects. Impaired attention, advanced age and a low l-dopa response at baseline predicted cognitive decline, whereas a high l-dopa response at baseline predicted an improvement in quality of life. Postoperative decrease in dopaminergic medication was not related to cognitive decline.
STN DBS improves quality of life. However, a profile of cognitive decline can be found in a significant number of patients. l-dopa response, age and attention at baseline are predictors of cognitive and psychosocial outcome.
Recent advances in the brain sciences have dramatically improved our understanding of brain function. As we find out more and more about what makes us tick, we must stop and consider the ethical implications of this new found knowledge. Will having a new biology of the brain through imaging make us less responsible for our behavior and lose our free will? Should certain brain scan studies be disallowed on the basis of moral grounds? Why is the media so interested in reporting results of brain imaging studies? What ethical lessons from the past can best inform the future of brain imaging? These compelling questions and many more are tackled by a group of contributors to this book on neuroethics. The wide range of disciplinary backgrounds that this book represents, from neuroscience, bioethics and philosophy, to law, social and health care policy, education, religion, and film, allow for profoundly insightful and provocative answers to these questions, and open up the door to a host of new ones. The contributions highlight the timeliness of modern neuroethics today, and assure the longevity and importance of neuroethics for generations to come.
Neuroscience has been described as a revolutionary force that will transform our understanding of common morality and of ethics as a discipline. To such strong naturalistic claims, critiques have responded with an arsenal of antinaturalistic arguments, often negating any contribution of neuroscience. In this paper, I review the terms of the debate between strong naturalists and anti-naturalists and offer a moderate (pragmatic) naturalistic approach as a constructive middle-ground position. Inspired by Dewey’s moral philosophy, I offer an alternate account of how neuroscience broadens our understanding of ethics and moral situations and thus supports a deliberative and iterative process of wisdom-generation.
The consideration of ethical and social issues related to current uses of deep brain stimulation (DBS) as well as investigational uses should now be an integral part of contemporary DBS practice. Scholarship, interdisciplinary work groups, and peer processes have helped articulate standards that need to be respected and implemented in current DBS practice. Integrating new knowledge and interdisciplinary ethical perspectives could be considered a sign of the maturity and rigor of a DBS program. Still, investigational uses of DBS carry tremendous hope but also touch on sensitive and thorny ethical questions. These questions can benefit from the ethical wisdom generated for standard uses of DBS but also challenge current practices and professional conduct. Realizing this, interdisciplinary expert groups have been convened to identify and flesh out ethical guideposts for cutting-edge research in DBS. By implementing these ethical frameworks, DBS is an opportunity to develop promising treatments for a set of vulnerable and sometimes underserved patients while keeping their best interests in sight.
Deep brain stimulation (DBS) has proven to be a successful therapeutic approach in several patients with movement disorders such as Parkinsońs disease and dystonia. Hitherto its application was mainly restricted to advanced disease patients resistant to medication or with severe treatment side effects. However, there is now growing interest in earlier application of DBS, aimed at improving clinical outcomes, quality of life, and avoiding psychosocial consequences of chronic disease-related impairments. We address the clinical and ethical aspects of two "early" uses of DBS, 1) DBS early in the course of the disease, and 2) DBS early in life (i.e. in children). Possible benefits, risks and burdens are discussed and thoroughly considered. Further research is needed to obtain a careful balance between exposing vulnerable patients to potential severe surgical risks and excluding them from a potentially good outcome.
In addition to medical treatment, deep brain stimulation has become an alternative therapeutic option in advanced Parkinson's disease. High initial costs of surgery have to be weighted against long-term gains in health-related quality of life. The objective of this study was to assess the cost-effectiveness of deep brain stimulation compared with long-term medical treatment. We performed a cost-utility analysis using a lifetime Markov model for Parkinson's disease. Health utilities were evaluated using the EQ-5D generic health status measure. Data on effectiveness and adverse events were obtained from clinical studies, published reports, or meta-analyses. Costs were assessed from the German health care provider perspective. Both were discounted at 3% per year. Key assumptions affecting costs and health status were investigated using one-way and two-way sensitivity analyses. The lifetime incremental cost-utility ratio for deep brain stimulation was €6700 per quality-adjusted life year (QALY) and €9800 and €2500 per United Parkinson's Disease Rating Scale part II (motor experiences of daily living) and part III (motor examination) score point gained, respectively. Deep brain stimulation costs were mainly driven by the cost of surgery and of battery exchange. Health status was improved and motor complications were reduced by DBS. Sensitivity analysis revealed that battery life time was the most influential parameter, with the incremental cost-utility ratio ranging from €20,000 per QALY to deep brain stimulation dominating medical treatment. Deep brain stimulation can be considered cost-effective, offering a value-for-money profile comparable to other well accepted health care technologies. Our data support adopting and reimbursing deep brain stimulation within the German health care system. © 2013 Movement Disorder Society.
Deep brain stimulation (DBS) is a well-established therapy for patients with advanced Parkinson's disease (PD) with clear benefits on many of the motor symptoms. The effects of DBS on the nonmotor symptoms are less well examined. Emergence of tools to measure the nonmotor burden in PD is now allowing a more objective assessment of impact of DBS on such symptoms. Here we review the pertinent evidence and conclude that, as a therapy, DBS has a major potential to contribute towards the holistic care of PD patients.
Despite the overall excellent outcome of neurosurgery in patients with Parkinson’s disease, there is often a contrast between
the improvement in motor disability and the difficulties of patients to reintegrate a normal life. In this study, the personal,
familial and professional difficulties experienced by patients two years after bilateral high frequency stimulation of the
subthalamic nucleus were carefully analyzed. To avoid such socio-familial maladjustment, we strongly suggest taking into consideration
the patients’ psychological and social context before the operation and during the post-operative follow-up.
Deep brain stimulation (DBS) is an accepted therapy for people with Parkinson's disease (PD) motor symptoms that are refractory to pharmacologic therapy. Standard DBS targets are globus pallidus interna (GPi) and subthalamic nucleus (STN). The pedunculopontine nucleus (PPN) is being investigated as a novel target. Which target provides the best outcomes is unknown.
The utility of GPi and STN as targets has been confirmed in numerous studies, including randomized comparisons of GPi DBS and STN DBS that demonstrated no difference in motor outcomes. DBS at either site improves appendicular motor symptoms, but beneficial effects on axial manifestations of PD such as postural instability or gait dysfunction (PIGD) are less apparent.
PPN has been introduced as a DBS target due to failure of GPi and STN DBS to improve PIGD. Small observational studies indicate improved PIGD with PPN DBS, but small blinded trials show only subjective reduction in falls with no other impact on PIGD or other PD manifestations.
No single DBS target is superior to the others. Each target offers relative advantages. Further studies are needed to better define the roles of each target, particularly PPN. Choice of target should be individualized according to providers' preferences and patients' needs.
Essential tremor (ET) is the most common movement disorder and often affects the quality of life. There are only a few studies evaluating the quality of life after deep brain stimulation (DBS).
This is a prospective study of 16 patients undergoing deep brain stimulation in the caudal Zona incerta (cZi). The quality of life was assessed with Quality of Life in Essential Tremor Questionnaire (QUEST) and SF-36 scores, and the tremor was evaluated using the essential tremor rating scale (ETRS).
In the tremor rating, hand tremor on the treated side improved by 95%, hand function by 78% and activities of daily living by 71%. The QUEST score showed statistically significant improvements in the psychosocial and activities of daily living subscores. The SF-36 score did not show any significant improvement.
Although very good tremor reduction was achieved, the improvement in the quality of life scores was more modest. This could partly be explained by the quality of life being affected by other factors than the tremor itself.
Objective: We evaluated trends in deep brain stimulation (DBS) for the 14-year period from 1993 to 2006.
Materials and Methods: We utilized the Nationwide Inpatient Sample data base from the Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality.
Results: A total of 34,792 patients underwent DBS surgery from 1993 to 2006. There were 756 DBS cases performed in 1993 compared with 4200 DBS procedures performed in 2006. Significant increases in nationwide DBS volume coincided with regulatory approval for new indications—Parkinson's disease and dystonia, respectively. Cost of DBS surgery increased from 69,329 in 2006. The majority of cases were done in metropolitan areas (97%) at large academic centers (91%) at a national bill of $291 MM.
Conclusions: Future studies will need to include the socioeconomic impact of the technology on disease status, patient access, and costs as it expands to novel indications.
The efficacy of deep brain stimulation (DBS) for the motor symptoms of advanced Parkinson's disease (PD) is well established. However, the effects of DBS on nonmotor symptoms (NMS) are less clear.
To review the published literature on nonmotor aspects of DBS for PD.
The outcome of NMS after DBS in PD varies across studies. Some symptoms improve -sleep disorders, pain or sensory complaints, obsessive-compulsive disorder- and other aspects decline or appear -word fluency, apathy, body weight gain-. Isolated studies note mild improvements in working memory, visuomotor sequencing and conceptual reasoning, some gastrointestinal, urogenital, sweating and olfactory disturbances; whereas other studies have reported declines in verbal memory (long delay recall), visuospatial memory, processing speed and executive function; orthostatic hypotension remains without changes. The reasons for such a range of symptoms observed is due to the multifactorial etiology of the NMS, including preoperative vulnerability, changes in dopaminergic medications, surgical and stimulation effects, underlying PD-related factors and psychosocial effects. Specific patient subgroups may be at greater risk of cognitive deficits -e.g., those older than 69 years or with cognitive impairment prior to surgery- or depression, mania and suicide -e.g., those ones with preoperative psychiatric symptoms-.
Patients who undergo DBS must be well-selected, weighing the risks and benefits, in order to obtain the best results with this treatment. Further multicentre studies are necessary to understand the role of DBS on NMS.
A worldwide cardiac pacing and implantable cardioverter-defibrillator (ICD) survey was undertaken for calendar year 2009 and compared to a similar survey conducted in 2005. There were contributions from 61 countries: 25 from Europe, 20 from the Asia Pacific region, seven from the Middle East and Africa, and nine from the Americas. The 2009 survey involved 1,002,664 pacemakers, with 737,840 new implants and 264,824 replacements. The United States of America (USA) had the largest number of cardiac pacemaker implants (225,567) and Germany the highest new implants per million population (927). Virtually all countries showed increases in implant numbers over the 4 years between surveys. High-degree atrioventricular block and sick sinus syndrome remain the major indications for implantation of a cardiac pacemaker. There remains a high percentage of VVI(R) pacing in the developing countries, although compared to the 2005 survey, virtually all countries had increased the percentage of DDDR implants. Pacing leads were predominantly transvenous, bipolar, and active fixation. The survey also involved 328,027 ICDs, with 222,407 new implants and 105,620 replacements. Virtually all countries surveyed showed a significant rise in the use of ICDs with the largest implanter being the USA (133,262) with 434 new implants per million population. This was the largest pacing and ICD survey ever performed, because of mainly a group of loyal enthusiastic survey coordinators. It encompasses more than 80% of all the pacemakers and ICDs implanted worldwide during 2009.
This study examined changes in motor function and quality of life (QoL) after subthalamic nuclei deep brain stimulation (STN-DBS) in patients with Parkinson disease (PD) and the role of psychosocial predictors on individual changes.
Forty-one patients with advanced PD (29 men and 12 women; mean age: 62.0 ± 8.0; disease duration: 14.5 ± 5.7) completed self-report questionnaires before surgery and at 6 and 12 months after surgery. Psychosocial measures assessed coping strategies (Ways of Coping Checklist-Revised), symptoms of depression (Beck Depression Inventory version II), anxiety (State-Trait Anxiety Inventory), and QoL (Parkinson Disease Questionnaire 39 Items, Medical Outcomes Study 36-Item Short-Form Health Survey).
After surgery, motor function (Unified Parkinson Disease Rating Scale III and IV), global QoL (Parkinson Disease Questionnaire 39 Items) and Physical Component Summary of the Medical Outcome Study Short Form 36-items Health Survey improved, whereas the Mental Component Summary tended to deteriorate. Depression and anxiety were stable. Improvements in motor function and QoL were associated with younger age, shorter duration of illness, higher baseline distress (depression and anxiety), and changes in problem-focused coping. Improvements in mental QoL were associated with a less frequent use of coping focused on seeking social support.
STN-DBS is associated with major positive changes in PD affecting motor function and QoL. These changes are related to psychological variables, including emotional distress and coping. A better focus on these individual characteristics is necessary to improve care of patients with PD who undertake STN-DBS.
Deep brain stimulation (DBS) has in some cases been associated with significant psychological effects and/or personality change. These effects occur sometimes as acute changes experienced intraoperatively or during the initial setting of the stimulator and sometimes as longer term progressive changes in the months following surgery. Sometimes they are the intended outcome of treatment, and in other cases they are an unintended side-effect. In all of these circumstances some patients and caregivers have described the psychological effects of DBS as frightening or disconcerting. I trace the source of these negative reactions to the fear that stimulation-related psychological and personality changes represent a threat to personal identity and agency. This issue has implications both for philosophical theories of personal identity and agency and for clinical concerns. A narrative account of personal identity is developed to illuminate the nature of the threat to identity and agency DBS potentially poses, and to suggest steps that might be taken to mitigate and avoid these threats.
Deep brain stimulation (DBS) of the globus pallidus interna and subthalamic nucleus has restored some degree of motor control in many patients in advanced stages of Parkinson's disease. DBS has also been used to treat dystonia, essential tremor (progressive neurological condition causing trembling), chronic pain, obsessive-compulsive disorder, Tourette's syndrome, major depressive disorder, obesity, cerebral palsy, and the minimally conscious state. Although the underlying mechanisms of the technique are still not clear, DBS can modulate underactive or overactive neural circuits and restore disrupted communication between and among groups of neurons in interacting regions of the brain.This can control and relieve many symptoms associated with a range of neurological and psychiatric disorders. But the procedures of implanting and stimulating the electrodes are brain-invasive and entail significant risks. Some patients receiving DBS have experienced intracerebral hemorrhage, infection, cognitive disturbances such as impulsive behavior, and affective disturbances such as mania. It is not known whether continuous electrical stimulation of the brain would reshape synaptic connectivity and permanently alter neural circuits in ways that may not be salutary. The risk of these effects indicates that DBS should be used only when a patient's condition is refractory to all other interventions and when there is a high probability that the technique will benefit the patient and improve his or her quality of life. If a patient's quality of life is poor and all other treatment options have been exhausted, then the likelihood of benefit can justify physicians' exposing patients to some risk. The clinical and ethical significance of the risk in DBS underscores the obligation of physicians to obtain fully informed consent from patients undergoing the procedure.
We report the 5 to 6 year follow-up of a multicenter study of bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) in advanced Parkinson's disease (PD) patients. Thirty-five STN patients and 16 GPi patients were assessed at 5 to 6 years after DBS surgery. Primary outcome measure was the stimulation effect on the motor Unified Parkinson's Disease Rating Scale (UPDRS) assessed with a prospective cross-over double-blind assessment without medications (stimulation was randomly switched on or off). Secondary outcomes were motor UPDRS changes with unblinded assessments in off- and on-medication states with and without stimulation, activities of daily living (ADL), anti-PD medications, and dyskinesias. In double-blind assessment, both STN and GPi DBS were significantly effective in improving the motor UPDRS scores (STN, P < 0.0001, 45.4%; GPi, P = 0.008, 20.0%) compared with off-stimulation, regardless of the sequence of stimulation. In open assessment, both STN- and GPi-DBS significantly improved the off-medication motor UPDRS when compared with before surgery (STN, P < 0.001, 50.5%; GPi, P = 0.002, 35.6%). Dyskinesias and ADL were significantly improved in both groups. Anti-PD medications were significantly reduced only in the STN group. Adverse events were more frequent in the STN group. These results confirm the long-term efficacy of STN and GPi DBS in advanced PD. Although the surgical targets were not randomized, there was a trend to a better outcome of motor signs in the STN-DBS patients and fewer adverse events in the GPi-DBS group.
In Parkinson disease (PD) patients, deep brain stimulation (DBS) of the subthalamic nucleus (STN) may contribute to certain impulsive behavior during high-conflict decisions. A neurocomputational model of the basal ganglia has recently been proposed that suggests this behavioral aspect may be related to the role played by the STN in relaying a "hold your horses" signal intended to allow more time to settle on the best option. The aim of the present study was 2-fold: 1) to extend these observations by providing evidence that the STN may influence and prevent the execution of any response even during low-conflict decisions; and 2) to identify the neural correlates of this effect.
We measured regional cerebral blood flow during a Go/NoGo and a control (Go) task to study the motor improvement and response inhibition deficits associated with STN-DBS in patients with PD.
Although it improved Unified Parkinson Disease Rating Scale motor ratings and induced a global decrease in reaction time during task performance, STN-DBS impaired response inhibition, as revealed by an increase in commission errors in NoGo trials. These behavioral effects were accompanied by changes in synaptic activity consisting of a reduced activation in the cortical networks responsible for reactive and proactive response inhibition.
The present results suggest that although it improves motor functions in PD patients, modulation of STN hyperactivity with DBS may tend at the same time to favor the appearance of impulsive behavior by acting on the gating mechanism involved in response initiation.
There is marked geographical variation in implantable cardioverter defibrillator (ICD) implantation rates in England. This study examined factors which might explain this variation.
Detailed data relating to 1510 patients who received an implanted defibrillator and who were reported to a national pacemaker and implantable defibrillator registry in 2002 were examined and correlated with factors which have been suggested as affecting ICD implantation. None of the factors examined, which included factors related both to the need for ICD implantation and service provision, in addition to socio-economic deprivation, was found to correlate with regional ICD implantation rates.
There appears to have been no systematic planning of ICD services. Whether this has led to the marked regional variation and in inequity of service provision is not clear.
Deep brain stimulation is an approved and effective neurosurgical intervention for motor disorders such as PD and ET. Deep brain stimulation may also be effective in treating a number of psychiatric disorders, including treatment refractory depression and OCD. Although DBS is a widely accepted therapy in motor disorders, it remains an invasive and expensive procedure. The ethical and social challenges of DBS need further examination, and discussion and emerging applications of DBS in psychiatry may also complicate the ethical landscape of DBS.
To identify and characterize current and emerging issues in the use of DBS, we reviewed the neurosurgical literature on DBS as well as the interdisciplinary medical ethics and relevant psychological and sociological literatures. We also consulted the USPTO database, FDA regulations and report decisions, and the business reports of key DBS manufacturers.
Important ethical and social challenges exist in the current and extending practice of DBS, notably in patient selection, informed consent, resource allocation, and in public understanding. These challenges are likely to be amplified if emerging uses of DBS in psychiatry are approved.
Our review of ethical and social issues related to DBS highlights that several significant challenges, although not insurmountable, need much closer attention. A combination of approaches previously used in neuroethics, such as expert consensus workshops to establish ethical guidelines and public engagement to improve public understanding, may be fruitful to explore.
Our aim was to compare in a prospective blinded study the cognitive and mood effects of subthalamic nucleus (STN) vs. globus pallidus interna (GPi) deep brain stimulation (DBS) in Parkinson disease.
Fifty-two subjects were randomized to unilateral STN or GPi DBS. The co-primary outcome measures were the Visual Analog Mood Scale, and verbal fluency (semantic and letter) at 7 months post-DBS in the optimal setting compared to pre-DBS. At 7 months post-DBS, subjects were tested in four randomized/counterbalanced conditions (optimal, ventral, dorsal, and off DBS).
Forty-five subjects (23 GPi, 22 STN) completed the protocol. The study revealed no difference between STN and GPi DBS in the change of co-primary mood and cognitive outcomes pre- to post-DBS in the optimal setting (Hotelling's T(2) test: p = 0.16 and 0.08 respectively). Subjects in both targets were less "happy", less "energetic" and more "confused" when stimulated ventrally. Comparison of the other 3 DBS conditions to pre-DBS showed a larger deterioration of letter verbal fluency in STN, especially when off DBS. There was no difference in UPDRS motor improvement between targets.
There were no significant differences in the co-primary outcome measures (mood and cognition) between STN and GPi in the optimal DBS state. Adverse mood effects occurred ventrally in both targets. A worsening of letter verbal fluency was seen in STN. The persistence of deterioration in verbal fluency in the off STN DBS state was suggestive of a surgical rather than a stimulation-induced effect. Similar motor improvement were observed with both STN and GPi DBS.
The vulnerability of patients receiving significantly innovative neurosurgical procedures, either as research or as non-standard therapy, presents particularly potent challenges for those attempting to substantially advance clinical Neurosurgical practice in the most ethically and efficacious manner. This beginning formulation has built into it several important notions about research participation, balancing values, and clinical advancement in the context of neurological illness. For the time being, allow vulnerability to act as a placeholder for circumstances or states of being wherein the established checks and balances of power and interest are no longer sufficient in promoting the just treatment of persons. Further, the phrase to substantially advance Neurosurgical practice encompasses radical innovation as well as significant research into new procedures. Finally, few of these explorations involve true randomized placebo controlled trials, but rather they enroll patients rightfully hoping for some benefit by means of undergoing the procedure.
When a neurosurgeon asks me, as an ethicist, to meet with a patient who has medically refractory disease and no good standard therapy options remaining, he is asking for help concerning whether to offer, as a last chance, an unproven therapy as either innovation or research.
Experimental studies suggest that deep brain stimulation (DBS) of the subthalamic nucleus (STN) induces impulsivity in patients with Parkinson's disease (PD). The purpose of this study was to assess various measures of impulse control in PD patients with STN DBS in comparison to patients receiving medical therapy.
In a cross-sectional evaluation, 53 consecutively eligible patients were assessed for impulsivity with the Barratt Impulsiveness Scale, for impulse control disorders (ICDs) using the Minnesota Impulsive Disorders Interview, and for obsessive-compulsive symptoms using the Maudsley Obsessional-Compulsive Inventory.
Independent samples t-tests revealed that compulsivity scores were not different between DBS patients and patients without DBS. However, impulsivity scores were significantly higher in DBS patients. Additionally, ICDs were observed in 3 of 16 (19%) DBS patients and in 3 of 37 (8%) medically treated patients. No association was found between the use of dopamine agonists and impulsivity in DBS patients.
Our data suggest that screening for impulsivity and ICDs should be performed prior to DBS, and that patients should be monitored for these problems during follow-up. Prospective trials are needed to confirm the findings of this exploratory study and to elucidate the reasons of a possible induction of impulsivity by STN DBS.
Within the recent development of brain-machine-interfaces deep brain stimulation (DBS) has become one of the most promising approaches for neuromodulation. After its introduction more than 20 years ago, it has in clinical routine become a successful tool for treating neurological disorders like Parkinson's disease, essential tremor and dystonia. Recent evidence also demonstrates efficacy in improving emotional and cognitive processing in obsessive-compulsive disorder and major depression, thus allowing new treatment options for treatment refractory psychiatric diseases, and even indicating future potential to enhance functioning in healthy subjects. We demonstrate here that DBS is neither intrinsically unethical for psychiatric indications nor for enhancement purposes. To gain normative orientation, the concept of "personality" is not useful--even if a naturalistic notion is employed. As an alternative, the common and widely accepted bioethical criteria of beneficence, non-maleficence, and autonomy allow a clinically applicable, highly differentiated context- and case-sensitive approach. Based on these criteria, an ethical analysis of empirical evidence from both DBS in movement disorders and DBS in psychiatric disease reveals that wide-spread use of DBS for psychiatric indications is currently not legitimated and that the basis for enhancement purposes is even more questionable. Nevertheless, both applications might serve as ethically legitimate, promising purposes in the future.
Chronic illness is perceived as a particular kind of event. The aim of this paper is to understand the personal, familial and professional difficulties experienced by patients in France who have a neurodegenerative disease and undergo cerebral implants. This paper is based on the assumption that a treatment using biotechnical techniques is a unique disruptive experience which redefines the patient's life. Thirty patients (13 women and 17 men) from two French hospitals were interviewed at different stages of their medical history. Despite the excellent overall outcome of neurosurgery in patients with Parkinson's disease, there is often a contrast between the improvement in motor disability and the patient's difficulty in returning to normal life. These results allow us to analyse the link between the neurosciences and the experience of chronic illness.
Little is currently known about the higher order functional skills of patients with Parkinson disease and cognitive impairment. Medical decision-making capacity (MDC) was assessed in patients with Parkinson's disease (PD) with cognitive impairment and dementia. Participants were 16 patients with PD and cognitive impairment without dementia (PD-CIND), 16 patients with PD dementia (PDD), and 22 healthy older adults. All participants were administered the Capacity to Consent to Treatment Instrument (CCTI), a standardized capacity instrument assessing MDC under five different consent standards. Parametric and nonparametric statistical analyses were utilized to examine capacity performance on the consent standards. In addition, capacity outcomes (capable, marginally capable, or incapable outcomes) on the standards were identified for the two patient groups. Relative to controls, PD-CIND patients demonstrated significant impairment on the understanding treatment consent standard, clinically the most stringent CCTI standard. Relative to controls and PD-CIND patients, PDD patients were impaired on the three clinical standards of understanding, reasoning, and appreciation. The findings suggest that impairment in decisional capacity is already present in cognitively impaired patients with PD without dementia and increases as these patients develop dementia. Clinicians and researchers should carefully assess decisional capacity in all patients with PD with cognitive impairment.
One hundred fifteen consecutive patients in the Austin Hospital Comprehensive Epilepsy Program (Melbourne, Australia) were surveyed to document the psychosocial and rehabilitation difficulties after temporal lobectomy. During the follow-up period (mean 4 years) 3 patients died, 5 patients were lost to follow-up, and 107 patients with family and friends were interviewed. Eighty-four patients (78%) had been seizure-free for the year preceding the interview; 13 others had seizure reduction greater than 75%. Success in ablation or reduction in seizures correlated with the amount of postoperative gain, but in this series, analysis of work and dependency outcome did not emphasize areas of success. Although improvement in work and financial status, interpersonal relations and sexuality were all recorded, successful patients deemed that most advance had been made in the areas of newly acquired independence, enhanced career potential, and social freedom. Significant postoperative anxiety, especially after left temporal lobectomy, was noted, possibly explained by benzodiazepine antiepileptic drug (AED) discontinuation. Although 1 patient committed suicide, neither depression nor psychosis was common in the rehabilitation period, in contrast to results in previous series. Significant sociodomestic problems emerged from this survey, however: 35% of patients considered successes reported postoperative problems stemming from the necessity to restructure family dynamics; in 6%, this resulted in divorce. Moreover, 20% of patients and relatives reported significant behavioral problems in coping with the seizure-free lifestyle. Finally, the problems of the worsened situation after surgical failure indicated the counterproductive potential of ineffective lobectomy. These results indicate the necessity for a preoperative counseling program to prevent these problems.
Stereotactic thalamotomy of the thalamic nucleus ventralis intermedius (VIM) is routinely used for movement disorders. During this procedure, it has been observed that high-frequency (100 Hz) stimulation of VIM was able to stop the extrapyramidal tremor. In patients with bilateral tremor of extrapyramidal origin, who were resistant to drug therapy, the therapeutic protocol associated (1) a radiofrequency VIM thalamotomy for the most disabled side, and (2) a continuous VIM stimulation for the other side using stereotactically implanted electrodes, connected to subcutaneous stimulators. VIM thalamotomy relieved the tremor in all operated cases. Side effects were mild and regressive. VIM stimulation strongly decreased the tremor but failed to suppress it as completely as thalamotomy did. This was due in part to the fact that programmable stimulator frequency rate is limited to 130 Hz, while it appeared that the optimal stimulation frequency was 200 Hz. This therapeutic protocol appears to be of interest for patients with bilateral extrapyramidal movement disorders.
Stereotactic thalamotomy of the VIM (ventral intermediate) nucleus is considered as the best neurosurgical treatment for Parkinsonian and essential tremors. However, this surgery, especially when bilateral, still presents a risk of recurrence and neurological complications. We observed that acute VIM stimulation at frequencies higher than 60 Hz during the mapping phase of the target suppressed the tremor of Parkinson's disease (PD) and essential tremor (ET). This effect was immediately reversible at the end of the stimulation. This was initially proposed as an additional treatment for patients already thalamotomized on the contralateral side, and then extended as a regular procedure for extra-pyramidal dyskinesias. Since January 1987, we implanted 126 thalami in 87 patients (61 PD, 13 ET, 13 dyskinesias of various origins). Deep brain stimulation electrodes were stereotactically implanted under local anaesthesia, using stimulation and micro-recording to delineate the best site of stimulation. Electrodes were subsequently connected to implantable programmable stimulators. The optimal frequency was around 130 to 185 Hz. The results (evaluated by a neurologist from 0 = no effect to 4 = perfect relief) are related to the type of tremor. Altogether, 71% of the 80 patients benefited from the procedure with grade 3 and 4 results. In 88% of the PD cases, the results were good (grade 3) or excellent (grade 4) and stable with time. Rigidity was moderately for a long improved but akinesia was not. The same level of improvement was observed in 68% of the ET patients and only in 18% of the other types of dyskinesias.(ABSTRACT TRUNCATED AT 250 WORDS)
Advances in neuromodulation techniques offer the promise of new therapeutic interventions for patients with neuropsychiatric maladies. Several complex social, ethical and policy issues will attend developments in this area. In this paper an ethical framework for clinical research in interventional cognitive neuroscience is advanced. Deep brain stimulation in traumatic brain injury is considered as a paradigm case to examine ethical obligations in human subject research. These include balancing access to novel therapies versus protection of vulnerable study populations, rational evaluation of study design and research strategies, informed consent, and the importance of achieving societal consensus for this line of scientific inquiry.
To assess neurologists' attitudes on rationing health care and to determine whether neurologists would set healthcare priorities in ways that are consistent with cost-effectiveness research.
Cost-effectiveness research can suggest ways to maximize health benefits within fixed budgets but is currently being underused in resource allocation decisions.
The authors surveyed a random sample of neurologists practicing in the United States (response rate, 44.4%) with three hypothetical scenarios. Two scenarios were designed to address general attitudes on allocating finite resources with emphasis on formulary decisions for costly drugs. The third scenario was designed to assess whether neurologists would optimize the allocation of a fixed budget as recommended by cost-effectiveness analysis.
Three-quarters of respondents thought that neurologists make daily decisions that effectively ration healthcare resources, and 60% felt a professional responsibility to consider the financial impact of individualized treatment decisions on other patients. Only 25% of respondents thought that there should be no restrictions placed on any of the five newer antiepileptic agents. In a 1995 survey, 75% of similarly sampled neurologists agreed that no restrictions should be placed on the availability of FDA-approved medications. Nearly half (46%) of respondents favored a less effective test and would be willing to let patients die to ensure the offering of a more equitable alternative.
Most neurologists recognize the need to ration health care, and although they think cost-effectiveness research is one method to achieve efficient distribution of resources, many think that considerable attention should also be given to equity.
The registry of the European Working Group on Cardiac Pacing (EWGCP) is based on the European Pacemaker Identification Card originally designed in July 1978. National registration centers collect the local data and send aggregated annual data to the EWGCP. For 1997, data were obtained from 2,887 hospitals in 20 European countries representing a population of 568 million. Across all participating countries, the median value for all implanted pacemakers was 378 per million population. For initial pacemaker implants, the median value was 290 per million population. Single chamber atrial pacing was important in Denmark, the Netherlands, Poland, Slovak Republic, Spain, and Sweden for the treatment of sick sinus syndrome. Dual chamber pacing accounted for < 50% of initial implants in only 5 of 14 countries for atrioventricular block, and in only 3 of 15 countries for sick sinus syndrome. In 7 of 15 countries, unipolar ventricular leads were used in > or = 50% of cases. In 6 of 14 countries, there was > 15% use of unipolar atrial leads. Nine of 13 countries frequently used atrial active-fixation leads. For the 1997 survey, ICD data were obtained from 16 countries. The total number of ICDs per million population was a median value of 14. Initial ICD implants per million population was 11. Only 3 of 16 countries implanted a total of 30 or more ICDs per million population. Pacing and ICD practices were dependent on the availability of medical and technical resources and influenced by economic constraints inherent in health care administration and insurance coverage patterns.
The present study investigated behavioural modifications and familiar relations in a group of 15 parkinsonian patients treated with bilateral deep brain stimulation of the subthalamic nucleus. In 70% of the patients, during the first months after surgery we observed a euphoric mood owing to motor signs amelioration, but a series of problems (fear to come back to the pre-operative condition, sense of failure, slowness in changing the old habits) arose when it was necessary to adjust the parameters of stimulation and the pharmacological therapy to obtain a stable clinical picture. The caregivers showed an aggressive behaviour as reaction to the persistent psychological dependence of the patients. This distressed condition could be the cause of the onset of incomprehensions within the couple.
Deep brain stimulation (DBS) in the subthalamic nucleus (STN) and the internal segment of the globus pallidus (GPi) is increasingly being used for the treatment of advanced Parkinson's disease (PD). Although both targets have demonstrated clinical efficacy in the treatment of the cardinal motor signs of PD, the STN has gained greater popularity and is now considered the site of choice by most centers performing these procedures. This preference stems predominately from the belief that STN DBS provides greater improvement in reducing the motor manifestations of PD and allows a reduction in dopaminergic medication not permitted with GPi DBS. There are, however, a number of issues that must be considered before abandoning GPi in favor of STN as the surgical target of choice for DBS. The maximal benefit reported for GPi stimulation is not significantly different than that reported for the STN, 67 versus 71%, and while reductions in medication are required with STN stimulation to avoid inducing dyskinesia, GPi stimulation may directly suppress dyskinesia obviating any need to reduce medication. As such, many centers may not attempt to reduce antiparkinsonian medication with GPi DBS. In addition, there are significantly more reports of changes in mood, behavior and a higher incidence of adverse events reported for STN stimulation. Most studies of DBS are nonrandomized, assessment protocols are not standardized, and lead locations are not reported. Thus, before drawing conclusions regarding the optimal site for DBS for advanced PD we must take a critical eye to the present data and address the outstanding questions that remain with well-designed clinical trials that evaluate motor, nonmotor and adverse events and address the above clinical variables by randomizing patients, using standardized methods of assessment and defining the lead location.