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Ying Meng and Nir Lipsman

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Daniel Mendelsohn, Nir Lipsman and Mark Bernstein

Object

Advances in the neurosciences are stirring debate regarding the ethical issues surrounding novel neurosurgical interventions. The application of deep brain stimulation (DBS) for treating refractory psychiatric disease, for instance, has introduced the prospect of altering disorders of mind and behavior and the potential for neuroenhancement. The attitudes of current and future providers of this technology and their position regarding its possible future applications are unknown. The authors sought to gauge the opinions of neurosurgical staff and trainees toward various uses of neuromodulation technology including psychosurgery and neuroenhancement.

Methods

The authors conducted a qualitative study involving in-depth interviews with 47 neurosurgery staff, trainees, and other neuroclinicians at a quaternary care center.

Results

Several general themes emerged from the interviews. These included universal support for psychosurgery given adequate informed consent and rigorous scientific methodology, as well as a relative consensus regarding the priority given to patient autonomy and the preservation of personal identity. Participants' attitudes toward the future use of DBS and other means of neuromodulation for cognitive enhancement and personality alteration revealed less agreement, although most participants felt that alteration of nonpathological traits is objectionable.

Conclusions

There is support in the neurosurgical community for the surgical management of refractory psychiatric disease. The use of neuromodulation for the alteration of nonpathological traits is morally and ethically dubious when it is out of sync with the values of society at large. Both DBS and neuromodulation will have far-reaching and profound public health implications.

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Nir Lipsman, Jocelyn Tolentino and R. Loch Macdonald

Object

Prognostic factors for outcome after aneurysmal subarachnoid hemorrhage (SAH) include the clinical and pathological characteristics of the patient and hemorrhage as well as some aspects of treatment. Because treatment can vary between countries and continents, the authors used a large database of patients with SAH to determine the effect of the geographic location of treatment on outcome.

Methods

Data obtained in 3567 patients who were entered into randomized trials of tirilazad between 1991 and 1997 were analyzed. Patients underwent treatment in 162 neurosurgical centers in 21 countries in North America, Europe, Africa, and Australia. The dependent variable was clinical outcome assessed 3 months after SAH with the Glasgow Outcome Scale, which was analyzed as a 5-point variable and dichotomized into favorable (good recovery or moderate disability) and unfavorable (severe disability, vegetative state, or death) outcomes. The effect of country or continent of treatment on outcome was assessed using univariate and multivariate logistic regression and proportional odds modeling before and after adjusting for numerous other factors significantly associated with outcome.

Results

The authors constructed several multivariate analysis models and demonstrated that for almost every model, country was not a significant predictor of outcome (p > 0.05). There was variation in outcome between countries, but this was mostly due to differences in other admission characteristics that influence outcome such as age, clinical grade, and subarachnoid clot thickness. Because the number of patients entered from some countries was small, countries were grouped, and the data were analyzed by continent. This grouping gave more stable estimates and created an appropriate model for both logistic and proportional odds models and again showed that continent had no significant effect on outcome.

Conclusions

Despite the variations in treatment that undoubtedly exist between countries and continents, the location of treatment had minimal effect on outcome. Outcome was influenced mostly by clinical characteristics on admission such as neurological grade, patient age, and amount of SAH.

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Benjamin Davidson, Lior M. Elkaim, Nir Lipsman and George M. Ibrahim

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Nir Lipsman and Andres M. Lozano

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Nir Lipsman, Abhaya V. Kulkarni and Osaama H. Khan

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Nir Lipsman, W. Jeffrey Elias, Ryder P. Gwinn and Julie G. Pilitsis

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Nir Lipsman, Mark Bernstein and Andres M. Lozano

There is an urgent need for an effective therapy for treatment-refractory mental illness. Trials ongoing globally that explore surgical treatment, such as deep brain stimulation, for refractory psychiatric disease have produced some promising early results. However, diverse inclusion criteria and variable methodological and ethical standards, combined with the sordid past of neuromodulation, confound trial interpretation and threaten the integrity of a new and emerging science. What is required is a standard of ethical practice, globally applied, for neurosurgical trials in psychiatry that protects patients and maintains a high ethical benchmark for clinicians and researchers to meet. With mental illness, as well as treatment resistance, reaching epidemic proportions, ethically and scientifically sound clinical trials will lead to effective and safe surgical treatments that will become vital components of the clinicians' armamentarium. Ethical criteria, such as the ones proposed here, need to be established now and applied in earnest if the field is to move forward and if patients with no other therapeutic options are to receive much-needed treatment.

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Nir Lipsman, Michael Ellis and Andres M. Lozano

Deep brain stimulation (DBS) has proven to be an effective and safe treatment option in patients with various advanced and treatment-refractory conditions. Thus far, most of the experience with DBS has been in the movement disorder literature, and more specifically in the adult population, where its use in conditions such as Parkinson disease has revolutionized management strategies. The pediatric population, however, can also be afflicted by functionally incapacitating neurological conditions that remain refractory despite the clinicians' best efforts. In such cases, DBS offers an additional treatment alternative. In this paper, the authors review their institution's experience with DBS in the pediatric population, and provide an overview of the literature on DBS in children. The authors conclude that DBS in children can and should be considered a valid and effective treatment option, albeit in highly specific and carefully selected cases.

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Marie-Andrée Coulombe, Lior M. Elkaim, Naif M. Alotaibi, Daniel A. Gorman, Alexander G. Weil, Aria Fallah, Suneil K. Kalia, Nir Lipsman, Andres M. Lozano and George M. Ibrahim

OBJECTIVE

Gilles de la Tourette syndrome (GTS) is a disorder characterized by motor and vocal tics. Although by definition the onset of GTS is before age 18 years, clinical trials of deep brain stimulation (DBS) have been conducted only in adults. Using individual participant data (IPD) meta-analysis methodology, the current study investigated the safety and efficacy of DBS as a treatment for GTS in children and youth.

METHODS

A systematic review with no date or language restrictions was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Three electronic databases were searched: PubMed, EMBASE, and Web of Science. From 843 articles screened, the IPD of 58 children and youth (ages 12–21 years) extracted from 21 articles were collected and analyzed. A mixed-effects univariable analysis followed by multivariable hierarchical regression was performed using change in the Yale Global Tic Severity Scale (YGTSS) score as the primary outcome and reported measures of comorbidities as secondary outcomes.

RESULTS

The authors’ results showed an average improvement of 57.5% ± 24.6% across studies on the YGTSS. They also found that comorbid depression and stimulation pulse width each correlated negatively with outcome (p < 0.05). In patients with less severe GTS, greater improvements were evident following thalamic stimulation. More than one-quarter (n = 16, 27.6%) of participants experienced side effects, the majority of which were minor.

CONCLUSIONS

DBS in the pediatric population may be an effective option with a moderate safety profile for treatment of GTS in carefully selected children and youth. Large, prospective studies with long-term follow-up are necessary to understand how DBS influences tic symptoms and may alter the natural course of GTS in children.