Ying Meng and Nir Lipsman
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.
Daniel Mendelsohn, Nir Lipsman, and Mark Bernstein
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.
The authors conducted a qualitative study involving in-depth interviews with 47 neurosurgery staff, trainees, and other neuroclinicians at a quaternary care center.
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.
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.
Nir Lipsman, W. Jeffrey Elias, Ryder P. Gwinn, and Julie G. Pilitsis
Nir Lipsman, Jocelyn Tolentino, and R. Loch Macdonald
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.
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.
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.
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.
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.
Nir Lipsman, Abhaya V. Kulkarni, and Osaama H. Khan
Nir Lipsman and Andres M. Lozano
Benjamin Davidson, Lior M. Elkaim, Nir Lipsman, and George M. Ibrahim
Ryan M. Jones, Shona Kamps, Yuexi Huang, Nadia Scantlebury, Nir Lipsman, Michael L. Schwartz, and Kullervo Hynynen
The object of this study was to correlate lesion size with accumulated thermal dose (ATD) in transcranial MRI-guided focused ultrasound (MRgFUS) treatments of essential tremor with focal temperatures limited to 50°C–54°C.
Seventy-five patients with medically refractory essential tremor underwent MRgFUS thalamotomy at the authors’ institution. Intraoperative MR thermometry was performed to measure the induced temperature and thermal dose distributions (proton resonance frequency shift coefficient = −0.00909 ppm/°C). In 19 patients, it was not possible to raise the focal temperature above 54°C because of unfavorable skull characteristics and/or the pain associated with cranial heating. In this patient subset, sonications with focal temperatures between 50°C and 54°C were repeated (5.1 ± 1.5, mean ± standard deviation) to accumulate a sufficient thermal dose for lesion formation. The ATD profile sizes (17, 40, 100, 200, and 240 cumulative equivalent minutes at 43°C [CEM43]) calculated by combining axial MR thermometry data from individual sonications were correlated with the corresponding lesion sizes measured on axial T1-weighted (T1w) and T2-weighted (T2w) MR images acquired 1 day posttreatment. Manual corrections were applied to the MR thermometry data prior to thermal dose accumulation to compensate for off-resonance–induced spatial-shifting artifacts.
Mean lesion sizes measured on T2w MRI (5.0 ± 1.4 mm) were, on average, 28% larger than those measured on T1w MRI (3.9 ± 1.4 mm). The ATD thresholds found to provide the best correlation with lesion sizes measured on T2w and T1w MRI were 100 CEM43 (regression slope = 0.97, R2 = 0.66) and 200 CEM43 (regression slope = 0.98, R2 = 0.89), respectively, consistent with data from a previous study of MRgFUS thalamotomy via repeated sonications at higher focal temperatures (≥ 55°C). Two-way linear mixed-effects analysis revealed that dominant tremor subscores on the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (CRST) were statistically different from baseline at 3 months and 1 year posttreatment in both low-temperature (50°C–54°C) and high-temperature (≥ 55°C) patient cohorts. No significant fixed effect on the dominant tremor scores was found for the temperature cohort factor.
In transcranial MRgFUS thalamotomy for essential tremor, repeated sonications with focal temperatures between 50°C and 54°C can accumulate a sufficient thermal dose to generate lesions for clinically relevant tremor suppression up to 1 year posttreatment, and the ATD can be used to predict the size of the resulting ablation zones measured on MRI. These data will serve to guide future clinical MRgFUS brain procedures, particularly those in which focal temperatures are limited to below 55°C.