Christiane Woopen

Deep brain stimulation as a new therapeutic approach in therapy-resistant mental disorders: ethical aspects of investigational treatment

Deep brain stimulation (DBS) is an established treatment option for some movement disorders, in particular Parkinson’s disease. Only recently, a number of promising studies with small samples of patients have been published in which impressive therapeutic outcomes achieved by DBS in otherwise treatment-resistant obsessive–compulsive disorder, major depression, and Tourette’s syndrome were reported. It seems probable that the investigational approach to treat mental disorders by DBS will increase substantially. Neurosurgical interventions in psychiatric patients raise ethical considerations not only based on the disreputable experiences of the era of psychosurgery. Therefore, it is necessary to implement transparent and well-defined regulations for the protection of the patients as well as appropriate support for therapeutic research. The current article aims to provide a synopsis of the DBS approach in mental disorders and the hitherto existing criteria for research. It suggests some additional requirements for ethically justifiable therapeutic research employing DBS in psychiatric patients.

Deep Brain Stimulation and the Search for Identity

Ethical evaluation of deep brain stimulation as a treatment for Parkinson’s disease is complicated by results that can be described as involving changes in the patient’s identity. The risk of becoming another person following surgery is alarming for patients, caregivers and clinicians alike. It is one of the most urgent conceptual and ethical problems facing deep brain stimulation in Parkinson’s disease at this time. In our paper we take issue with this problem on two accounts. First, we elucidate what is meant by “becoming another person” from a conceptual point of view. After critically discussing two broad approaches we concentrate on the notion of “individual identity” which centers on the idea of “core attitudes”. Subsequently we discuss several approaches to determine what distinguishes core attitudes from those that are more peripheral. We argue for a “foundational-function model” highlighting the importance of specific dependency relations between these attitudes. Our second aim is to comment on the possibility to empirically measure changes in individual identity and argue that many of the instruments now commonly used in selecting and monitoring DBS-patients are inappropriate for this purpose. Future research in this area is advised combining a conceptual and an empirical approach as a basis of sound ethical appraisal.

Patients’ expectations of deep brain stimulation, and subjective perceived outcome related to clinical measures in Parkinson's disease: a mixed-method approach

Objective To study patients’ expectations of subthalamic deep brain stimulation (STN-DBS) and their subjective perceived outcome, by using qualitative and quantitative methods in Parkinsons disease (PD). Methods PD patients were prospectively examined before and 3 months after surgery. Semistructured interviews regarding preoperative expectations and postsurgical subjective perceived outcome were conducted. These were analysed using content analysis. For statistical analyses, patients were classified according to their subjective perceived outcome, resulting in three different subjective outcome groups (negative, mixed, positive outcome). The groups were used for multiple comparisons between and within each group regarding motor impairment, quality of life (QoL), neuropsychiatric status and cognitive functioning, using standard instruments. A logistic regression analysis was conducted to find predictors of subjective negative outcome. Receiver operating characteristic curves were used to analyse cut-off scores for predictive tests. Results Of the 30 PD patients participating, 8 had a subjective negative outcome, 8 a mixed and 14 a positive outcome. All groups significantly improved in motor functioning. Patients with subjective negative outcome were characterised by preoperative unrealistic expectations, no postsurgical improvement in QoL, and significantly higher presurgical and postsurgical apathy and depression scores. Higher preoperative apathy and depression scores were significant predictors of negative subjective outcome. Cut-off scores for apathy and depression were identified. Conclusions The mixed-method approach proved useful in examining a patients subjective perception of STN-DBS outcome. Our results show that significant motor improvement does not necessarily lead to a positive subjective outcome. Moreover, PD patients should be screened carefully before surgery regarding apathy and depression. (DRKS-ID: DRKS00003221).

Motor Improvement and Emotional Stabilization in Patients With Tourette Syndrome After Deep Brain Stimulation of the Ventral Anterior and Ventrolateral Motor Part of the Thalamus.

BACKGROUND Since its first application in 1999, the potential benefit of deep brain stimulation (DBS) in reducing symptoms of otherwise treatment-refractory Tourette syndrome (TS) has been documented in several publications. However, uncertainty regarding the ideal neural targets remains, and the eventuality of so far undocumented but possible negative long-term effects on personality fuels the debate about the ethical implications of DBS. METHODS In this prospective open-label trial, eight patients (three female, five male) 19-56 years old with severe and medically intractable TS were treated with high-frequency DBS of the ventral anterior and ventrolateral motor part of the thalamus. To assess the course of TS, its clinical comorbidities, personality parameters, and self-perceived quality of life, patients underwent repeated psychiatric assessments at baseline and 6 and 12 months after DBS onset. RESULTS Analysis indicated a strongly significant and beneficial effect of DBS on TS symptoms, trait anxiety, quality of life, and global functioning with an apparently low side-effect profile. In addition, presurgical compulsivity, anxiety, emotional dysregulation, and inhibition appeared to be significant predictors of surgery outcome. CONCLUSIONS Trading off motor effects and desirable side effects against surgery-related risks and negative implications, stimulation of the ventral anterior and ventrolateral motor part of the thalamus seems to be a valuable option when considering DBS for TS.

Informed consent in deep brain stimulation - ethical considerations in a stress field of pride and prejudice.

The story of psychosurgery is one of great visions, groundbreaking ideas, and heroic acts; similarly it is a story of a great rise, a deep fall, and a cautious resurrection. For a long time, psychosurgery mainly had an experimental character and was dominated by anecdotal reports. In the aftermath of Fulton and Jabobsens presentation of their results of a series of neurosurgical experiments performed with primates (Kopell and Rezai, 2003) during the International Neurological Congress in London in 1935, a considerable amount of ethically as well as scientifically doubtful surgical interventions were carried out in humans, occasionally even by medically uneducated personnel (Feldman and Goodrich, 2001). In this context one might paradigmatically mention prefrontal lobotomies, which virtually were advertised as magic bullet for all sorts of psychiatric diseases mainly in the 1940s and 1950s (Feldman et al., 2001; Kopell and Rezai, 2003; Mashour et al., 2005). Issues of informed consent frequently were neglected (Feldman and Goodrich, 2001; Pippard, 2001; Huys et al., 2010), critical side effects of the operation were concealed in many cases (Feldman and Goodrich, 2001) and the procedure even was offered to patients considered as criminally insane in exchange for their freedom (Lowinger, 1987). It was not long after Egas Moniz shared the Nobel Prize for medicine “for his discovery of the therapeutic value of prefrontal leucotomies in certain psychoses” in 1949 (Anonymous, 1949) when the public opinion of psychosurgery changed and questionable practices were unmasked (Heller et al., 2006). Prompted by growing public criticism, a lack of a sufficient theoretical foundation, the uncertainty of its therapeutic value and severe side effects, the Department of Health, Education, and Welfare (Public Health Service) released strict restrictions regarding the usage of leucotomy in 1978 (Department of Health, Education, and Welfare, 1978); back then, many other nations already had prohibited this technique. While in the aftermath of the approval of chlorpromazine as first medicament for the treatment of psychiatric diseases in 1954 psychopharmacological therapy progressively began to revolutionize the psychiatric world, surgical methods for the treatment of psychiatric diseases involving gross damage of brain tissue were abandoned. However, encouraged by former success with invasive methods and supported by a growing knowledge regarding neuroanatomy and neural circuits underlying psychiatric and neurological diseases, novel and innovative surgical techniques came up. By now the somewhat prestressed term “psychosurgery” gave way to the broader idea of “neuromodulation,” which summarizes not only invasive methods like deep brain stimulation (DBS) and vagus nerve stimulation, but also non-invasive techniques such as transcranial magnetic stimulation. The ambivalent history of psychosurgery in mind, it is utterly comprehensible that even a reversible though (minimally) invasive technique like DBS reactivates ancient fears. Furthermore, with the observation of psychiatric side effects following DBS of the subthalamic nucleus in patients suffering from Parkinsons disease in the late 1990s (Bejjani et al., 1999; Hariz et al., 2010; Kuhn et al., 2010) psychiatric diseases came in the focus of DBS. Particularly since this amelioration of possible indications of DBS, the to some extent disreputable inheritance of psychosurgery has been brought up frequently. However, DBS has not only proven to be an effective tool for the therapy of movement disorders such as Parkinsons disease, essential tremor, and dystonia, but it also has been successfully applied for the treatment of various psychiatric disorders such as obsessive-compulsion disorder (OCD), depression, Gilles-de-la-Tourette Syndrome, alcoholism, minimal conscious states, and Alzheimers dementia. (Freund et al., 2009; Kuhn et al., 2010; Laxton et al., 2010). A considerable amount of ethical skepticism culminates in the question of whether and how patients suffering from occasionally debilitating psychiatric diseases are capable of giving fully and freely their informed consent to a partly experimental procedure like DBS; we use the term “experimental” with precaution, but it should be kept in mind that there still is a considerable need for further research especially on its long-term therapeutic value with respect to its usage in psychiatric disorders (Hall and Carter, 2011). Particularly patients with Alzheimers disease may be limited in certain cognitive dimensions and this restriction could endanger their ability to completely understand all the implications connected with DBS. Beyond that, cognitive impairment is a common finding in patients with depression which could be linked to a dysfunction of the prefrontal cortex in interaction with subcortical regions (Clark et al., 2009); this dysfunction may result in deficits of attention, perception, concentration, and memory, hereby leading to a significant ambivalence of the patient. Moreover, patients suffering from substance abuse frequently are impaired with respect to tasks that involve highly goal-directed behavior; just recently it has been hypothesized that this deficit may be a result of a dysfunctional hypocretin system in the lateral thalamus (Boutrel et al., 2010). Due to this psychiatric condition, these patients might be constricted in their free decision making process. Furthermore, many questions regarding DBS are still unanswered yet, for which reason it frequently is considered as a last resort when other therapeutic strategies could not be of substantial help. In this situation the desperate hope for ultimate relief may unduly affect a patients ability to give his or her consent (Glannon, 2010): this aspect exemplarily is emphasized by the fact that OCD patients have to suffer up to 8 h a day from typical symptoms of their disease to be accepted as possible candidates for DBS (Glannon, 2010). Additionally, the medias perception of DBS and its therapeutic potential tend to be euphoric and occasionally too optimistic. Contrariwise, psychosurgerys frightful history not infrequently is picked out as the central theme of novels and movies (cp. “One Flew Over the Cocoos Nest,” 1975 or “Shutter Island,” 2010), which might be a source of inadequate fright for patients and their family members. We go along with Lang and Widners (2002) suggestion that “surgery should never be offered to a patient until … [a] realistic understanding is fully established.” Beauchamp and Childress (2001) and Berg et al. (2001) found that informed consent implies three basic requests: (1) all medically relevant information about diagnosis and prognosis of a patients disease, the therapy, its potential risks and alternative therapies must be disclosed. (2) The patient should have the mental capacity to understand his or her situation and the presented information. (3) The patient must not be coerced or compelled, but autonomously decides about a treatment on the basis of the information disclosed. Regarding what has been discussed above, a patient and his or her family members might be prejudiced and influenced in many ways considering DBS. In addition, due to the underlying psychiatric disease, the patient might lack the mental capacity to fully comprehend his or her condition. Considering all this, envisaging DBS bears the risk that a patients autonomy, i.e., his or her capacity to determine freely what action should be taken, if any, might be endangered. The concept of autonomy is closely connected to personal uniqueness (Breden and Vollmann, 2004) – so what if this uniqueness is affected by disease and possibly by prejudice as well? Even though this challenge is not unique to DBS or even to DBS in psychiatric diseases, the specific history of DBS, the complex connotations of a patient suffering from a psychiatric illness and potentially existing prejudice of the patient or his or her relatives, urgently call for detailed ethical examinations, highly skilled physicians, and more specific instruments for the assessment of a patients capacity. The MacArthur Competence Assessment Tool-Treatment (MacCAT-T) currently is regarded as psychiatrys gold standard for the determination of a patients decision making competence. However, it has been reasonably criticized: the underlying construct of “competence” evaluated by the MacCAT-T is dominated by cognitive criteria, whereas emotional and biographical factors and a patients values are ignored, although these dimensions might be of substantial importance during a decision making process (Breden and Vollmann, 2004). No alternative tool has been developed so far, so there is a high and urgent need for further endeavor in the design of proper assessment tools, which should include an extension of the cognition-based construct of competence proposed by the MacCAT-T.

Law and ethics of deep brain stimulation.

Deep brain stimulation (DBS) is a non-destructive, adjustable, and mainly reversible method of continuously giving electrical impulses into a small area of the brain via implanted electrodes. It has been established as a standard form of treatment for specific cases of Parkinsons disease, essential tremor and dystonia. It is currently being evaluated for several mental disorders, dementia and even alcoholism. In spite of its growing practical importance, the legal issues have so far undergone almost no analysis. The article outlines both the essential legal questions of DBS from the perspective of German Law as well as major issues of the current ethical debate, and the correlation of both fields.

Subjective perceived outcome of subthalamic deep brain stimulation in Parkinson's disease one year after surgery

OBJECTIVES Dissatisfaction with subthalamic deep brain stimulation (STN-DBS) despite motor improvements has been observed in Parkinsons disease (PD). Hence, we compared patients subjective perceived outcome 12 months after surgery (12mFU) with clinical measures to identify risk factors of dissatisfaction. METHODS Patients were examined at baseline and 12mFU. Quality of life (QoL), neuropsychiatric, cognitive and neurological functioning was measured. Patients were classified concerning their subjective outcome (negative = dissatisfaction; mixed; positive = satisfaction) at 12mFU using semi-structured interviews. First, the three groups were compared concerning interview statements. Second, repeated measures ANOVAs with group as between-subjects factor were applied to find significant effects of time, group, or interaction. Third, binary logistic regression determined predictors of dissatisfaction. RESULTS Of the 28 enrolled patients, 25% perceived their outcome as negative, 32.1% as mixed, and 42.9% as positive. Concerning interview statements, dissatisfied patients mentioned significantly less often improved QoL and reduced medication, and reported worsening of mental state, and social interaction. For the whole sample, significant improvement over time was found for motor functioning, daily dopamine dosages, and QoL. Apathy significantly worsened over time, but dissatisfied patients were overall more apathetic and depressed than the other groups. Significant interaction of group and time was identified for QoL, which only improved in the mixed and satisfied group. Finally, preoperative apathy and axial symptoms predicted dissatisfaction with STN-DBS. CONCLUSIONS Although motor symptoms and QoL improved in the whole sample, 25% of patients showed disappointment with STN-DBS. Especially apathy predicts dissatisfaction and should be considered preoperatively.

An Ethical Framework for Outcome Assessment in Psychiatric DBS

Deep brain stimulation (DBS) is an up-and-coming therapeutic approach in psychiatry. Although recent studies have demonstrated that DBS is relatively safe, little is known about its impact on a patients life. A comprehensive outcome assessment is required so as to ensure valid scientific findings for the proper counseling of future patients; a thorough benefit–harm assessment plays an important role in planning of the therapeutic process. Starting from a basic anthropological and ethical premise, disorder-specific and intervention-related parameters concerning a wide range of data relating to the individual person would need to be amassed. These data can be collected by means of a combination of quantitative tests and qualitative interviews, including the perspective of the patient and of a closely related person. They can be presented using codes from the WHO International Classification of Functioning, Disability and Health (ICF). An international consensus group on outcome assessment and coding according to the ICF could be established in psychiatric DBS.

PREFERTILIZATION DIAGNOSIS : A PROPOSAL FOR A REVISED NOMENCLATURE

A new term should be introduced into the discussion of the various ethical and legal concerns associated with the process of preimplantation diagnosis. The aim is both to aid communication within the field and to distinguish sufficiently between different aspects of the processes involved. The term prefertilization diagnosis could be used to describe the methods used to perform tests on gametes before fertilization; these tests previously have been referred to as preimplantation or preconception diagnosis. The aim of preimplantation diagnosis, which developed in the United Kingdom in the mid-1980s within the framework of IVF, is to test cells taken from a 3-day-old embryo in the 6- to 10-cell stage for the presence of genetically caused disorders or dispositions or to establish the sex of the embryo if there is a possibility of a sex-related genetic disorder. These tests are performed before ET is undertaken to enable the selection of the best embryos to be implanted.

Communicating with parents in neonatal intensive care units: The impact on parental stress

OBJECTIVE To analyse stress in parents whose infants with very low birth weight have just concluded high-level care in a Neonatal Intensive Care Unit (NICU). More specifically, we aimed 1) to identify groups of parents in the NICU who are particularly at risk of experiencing stress, and 2) to explore the effects of clinical staffś communication on parental stress. METHODS Our multi-center-study evaluated views from 1277 parents about care for 923 infants in 66 German NICUs. Answers were linked with separately evaluated medical outcomes of the infants. Separate generalised mixed models estimated the influence of personal, medical and communication-related characteristics on specific parental stress. RESULTS Parents of a younger age and those of infants with severe prognoses were more likely to experience stress. While empathetic communication as one aspect of staffś communication was shown as appropriate in reducing parental stress, an initial introduction and the quantity of information were only slightly associated with lower levels of stress. CONCLUSION Results provide evidence for the need to involve parents empathetically from the beginning of their childs stay in the NICU. PRACTICE IMPLICATIONS Staff in the NICU should communicate empathetically and help to reduce stress in parents particularly at risk.