Brian H. Kopell

Complications of deep brain stimulation surgery

Although technological advances have reduced device-related complications, DBS surgery still carries a significant risk of transient and permanent complications. We report our experience in 86 patients and 149 DBS implants. Patients with Parkinson’s disease, essential tremor and dystonia were treated. There were 8 perioperative, 8 postoperative, 9 hardware-related complications and 4 stimulation-induced side effects. Only 5 patients (6%) sustained some persistent neurological sequelae, however, 26 of the 86 patients undergoing 149 DBS implants in this series experienced some untoward event with the procedure. Although there were no fatalities or permanent severe disabilities encountered, it is important to extend the informed consent to include all potential complications.

Deep Brain Stimulation for Parkinson's Disease: Surgical Technique and Perioperative Management

Deep brain stimulation (DBS) is a widely accepted therapy for medically refractory Parkinsons disease (PD). Both globus pallidus internus (GPi) and subthalamic nucleus (STN) stimulation are safe and effective in improving the symptoms of PD and reducing dyskinesias. STN DBS is the most commonly performed surgery for PD as compared to GPi DBS. Ventral intermediate nucleus (Vim) DBS is infrequently used as an alternative for tremor predominant PD patients. Patient selection is critical in achieving good outcomes. Differential diagnosis should be emphasized as well as neurological and nonneurological comorbidities. Good response to a levodopa challenge is an important predictor of favorable long‐term outcomes. The DBS surgery is typically performed in an awake patient and involves stereotactic frame application, CT/MRI imaging, anatomical targeting, physiological confirmation, and implantation of the DBS lead and pulse generator. Anatomical targeting consists of direct visualization of the target in MR images, formula‐derived coordinates based on the anterior and posterior commissures, and reformatted anatomical stereotactic atlases. Physiological verification is achieved most commonly via microelectrode recording followed by implantation of the DBS lead and intraoperative test stimulation to assess benefits and side effects. The various aspects of DBS surgery will be presented.

Deep brain stimulation for psychiatric disorders.

Over the last decade, deep brain stimulation (DBS) has revolutionized the practice of neurosurgery, particularly in the realm of movement disorders. It is no surprise that DBS is now being studied in the treatment of refractory psychiatric disease. Deep brain stimulation has inherent advantages over previous lesioning procedures. It is fully reversible, and stimulation can be adjusted according to a patients changing symptoms and disease progression. Coupled with the fact that the stimulation can generally be turned on or off without the patients awareness, DBS provides a unique opportunity for double-blinding studies. To undertake DBS for psychiatric conditions, appropriate surgical targets must be chosen. What is most strongly supported is the role of cortico-striato-thalamocortical (CSTC) loops in the pathophysiology of psychiatric symptoms. Recent functional imaging studies have consistently found evidence that corroborate this model of psychiatric symptom pathogenesis. Based on the psychiatric and cognitive effects seen in recent movement disorder surgery, it is apparent that modulation of neural systems subserving psychiatric phenomenon can be accomplished by DBS. The few published studies on DBS for obsessive-compulsive disorder (OCD) suggest that this can be done safely. While efficacy data are still uncertain, initial data are promising.

Deep brain stimulation for Parkinson's disease: Surgical issues

Numerous factors need to be taken into account when implanting deep brain stimulation (DBS) systems into patients with Parkinsons disease. The surgical procedure itself can be divided into immediate preoperative, intraoperative, and immediate postoperative phases. Preoperative considerations include medication withdrawal issues, stereotactic equipment choices, imaging modalities, and targeting strategy. Intraoperative considerations focus on methods for physiological confirmation of a given target for DBS electrode deployment. Terms such as microelectrode recording, microstimulation, and macrostimulation will be defined to clarify inconsistencies in the literature. Advantages and disadvantages of each technique will be addressed. Furthermore, operative decisions such as staging, choice of electrode and implantable pulse generator, and methods of device fixation will be outlined. Postoperative issues include imaging considerations, including magnetic resonance safety, device–device interactions, and immediate surgical complications pertaining to the DBS procedure. This report outlines answers to a series of questions developed to address all aspects of the DBS surgical procedure and decision‐making with a systematic overview of the literature (until mid‐2004) and by the expert opinion of the authors. This is a report from the Consensus on Deep Brain Stimulation for Parkinsons Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society. It outlines answers to a series of questions developed to address all surgical aspects of deep brain stimulation.

Subfascial Implantation of Intrathecal Baclofen Pumps in Children: Technical Note

OBJECTIVEIndwelling intrathecal drug delivery systems are becoming increasingly important as a method of neuromodulation within the nervous system. In particular, intrathecal baclofen therapy has shown efficacy and safety in the management of spasticity and dystonia in children. The most common complications leading to explantation of the pumps are skin breakdown and infection at the pump implantation site. The pediatric population poses particular challenges with regard to these complications because appropriate candidates for intrathecal baclofen therapy are often undernourished and thus have a dearth of soft tissue mass to cover a subcutaneously implanted baclofen pump. We report a technique of subfascial implantation that provides greater soft tissue coverage of the pump, thereby reducing the potential for skin breakdown and improving the cosmetic appearance of the implantation site. METHODSEighteen consecutively treated children (average age, 8 yr, 7 mo) with spasticity and/or dystonia underwent subfascial implantation of a baclofen pump. These children’s mean weight of 42.9 lb is less than the expected weight for a group of children in this age group, ranging from 4 years, 8 months, to 15 years, 7 months. In all patients, the pump was inserted into a pocket surgically constructed between the rectus abdominus and the external oblique muscles and the respective anterior fascial layers. RESULTSAt an average follow-up of 13.7 months, no infection or skin breakdown had occurred at the pump surgical site in any of the 18 patients. CONCLUSIONAt this early follow-up, the subfascial implantation technique was associated with a reduced rate of local wound and pump infections and provided optimal cosmetic results as compared with that observed in retrospective cases.

Feasibility of auditory cortical stimulation for the treatment of tinnitus.

Objectives: To investigate the feasibility and safety of an implantable epidural cortical stimulator for the treatment of severe tinnitus. Study Design: Prospective, controlled, single-blinded study of cortical stimulation for 4 weeks, and then an open-label stimulation period. Setting: Tertiary care referral center. Patients: Adults (n = 8) with constant tinnitus of at least 1 year with a tinnitus reaction questionnaire score greater than 33. Tinnitus was predominantly unilateral with a frequency less than 8,000 Hz. Interventions: Surgical implantation of an investigational epidural electrode over the posterior superior temporal gyrus using functional magnetic resonance imaging targeting. A 2-week stimulation period alternated with a 2-week sham period in random order to which subjects were blinded. This was followed by continuous stimulation with parameter adjustments to maximize tinnitus suppression. Main Outcome Measure: Subjective rating of tinnitus severity, loudness, and device efficacy. Objective measures of hearing thresholds, tinnitus frequency, loudness, and minimum masking levels. Outcome measures using the Tinnitus Handicap Questionnaire, Tinnitus Reaction Questionnaire, and Beck Depression Inventory. Results: There were no effects of stimulation during the 4-week blinded period. With continuous chronic stimulation, 2 patients had persistent reduction of pure-tone tinnitus, and 6 patients had short periods of total tinnitus suppression.Significant improvements in the Beck Depression Inventory and tinnitus questionnaires were found, although objective measures of tinnitus loudness remained fairly stable. No surgical or stimulation-related complications were noted. Conclusion: Chronic electrical stimulation of the secondary auditory cortex seems safe and warrants further investigation as a potential therapeutic intervention for the suppression of tinnitus.

Epidural cortical stimulation of the left dorsolateral prefrontal cortex for refractory major depressive disorder.

BACKGROUND A significant number of patients with major depressive disorder are unresponsive to conventional therapies. For these patients, neuromodulation approaches are being investigated. OBJECTIVE To determine whether epidural cortical stimulation at the left dorsolateral prefrontal cortex is safe and efficacious for major depressive disorder through a safety and feasibility study. METHODS Twelve patients were recruited in this randomized, single-blind, sham-controlled study with a 104-week follow-up period. The main outcome measures were Hamilton Depression Rating Scale-28 (HDRS), Montgomery-Asberg Depression Rating Scale (MADRS), Global Assessment of Function (GAF), and Quality of Life Enjoyment and Satisfaction (QLES) questionnaire. An electrode was implanted over Brodmann area 9/46 in the left hemisphere. The electrode provided long-term stimulation to this target via its connections to an implanted neurostimulator in the chest. RESULTS During the sham-controlled phase, there was no statistical difference between sham and active stimulation, although a trend toward efficacy was seen with the active stimulation group. In the open-label phase, we observed a significant improvement in outcome scores for the HDRS, MADRS, and GAF but not the QLES (HDRS: df = 7, F = 7.72, P < .001; MADRS: df = 7, F = 8.2, P < .001; GAF: df = 5, F = 16.87, P < .001; QLES: df = 5, F = 1.32, P > .2; repeated measures ANOVA). With regard to the HDRS, 6 patients had ≥ 40% improvement, 5 patients had ≥ 50% improvement, and 4 subjects achieved remission (HDRS < 10) at some point during the study. CONCLUSION Epidural cortical stimulation of the left dorsolateral prefrontal cortex appears to be a safe and potentially efficacious neuromodulation approach for treatment-refractory major depressive disorder. ABBREVIATIONS DBS: deep brain stimulation DLPFC: dorsolateral prefrontal cortex ECT: electroconvulsive therapy EPCS: epidural cortical stimulation FDA: Food and Drug Administration FDG: fluorodeoxyglucose GAF: Global Assessment of Functioning HDRS: Hamilton Depression Rating Scale-28 MADRS: Montgomery-Asberg Depression Rating Scale MDD: major depressive disorder QLES: Quality of Life Enjoyment and Satisfaction questionnaire rCMRG: regional cerebral metabolic rate of glucose TMS: transcranial magnetic stimulation VNS: vagus nerve stimulation

History of psychosurgery: a psychiatrist's perspective.

Interest in using neuromodulation to treat psychiatric disorders is rapidly increasing. The development of novel tools and techniques, such as deep brain stimulation (DBS), increases precision and minimizes risk. This article reviews the history of psychosurgical interventions and recent developments of DBS to provide a framework for understanding current options and future goals. We begin by discussing early approaches to psychosurgery, focusing on the widespread use of lobotomy and the subsequent backlash from the public and professionals in the field. Next, we discuss the development of stereotaxis. This technique allows for more targeted, precise interventions that produce discrete subcortical lesions. We focus on four stereotactic procedures that were developed using this technique: cingulotomy, capsulotomy, subcaudate tractotomy, and limbic leucotomy. We subsequently review contemporary theory and approaches with relevance to psychosurgery. We discuss the systems and neurocircuitry that are thought to be involved in psychiatric illness and provide targets for intervention. This discussion includes presentation of basal ganglia thalamocortical pathophysiology including cortico-striato-thalamo-cortical loops. We focus the discussion on two psychiatric disorders that have been targets of neurosurgical interventions: obsessive-compulsive disorder and mood disorders such as major depressive disorder. Evidence from studies of DBS in psychiatric disorders, including efficacy and tolerability, is reviewed. Finally, we look to the future, exploring the possibilities for these approaches to increase understanding, transform societal views of mental illness, and improve treatment.

Deep brain stimulation for obsessive-compulsive disorder: Using functional magnetic resonance imaging and electrophysiological techniques: Technical case report

OBJECTIVE AND IMPORTANCE To demonstrate the pattern of activation associated with electrical stimulation through bilateral deep brain stimulation electrodes placed within the anterior limb of the internal capsule to the level of the ventral striatum for treatment of obsessive-compulsive disorder. CLINICAL PRESENTATION A 44-year-old man with a 26-year history of obsessive-compulsive disorder underwent functional magnetic resonance imaging (fMRI) and deep brain stimulation-evoked cortical potential testing after bilateral implantation of deep brain stimulation leads. Stimulation was delivered independently through the distal two contacts of each percutaneously extended lead using an external pulse generator. On postoperative Day 2, we used a 3-Tesla magnetic resonance system to measure changes in the fMRI blood oxygen level-dependent signal using stimulation parameters that were predetermined to demonstrate behavioral effects. INTERVENTION All studies were well tolerated. Trial stimulations performed intraoperatively as well as on postsurgical Day 1 were associated with acutely elevated mood and reduced anxiety. Although the benefit achieved acutely was relatively symmetric between the bilaterally placed leads, follow-up programming showed a clear advantage to right-sided stimulation. Three of the four fMRI trials demonstrated good activation, with the fourth being moderately corrupted by motion artifact. The beneficial effects observed with right-sided stimulation were associated with activation of the ipsilateral head of the caudate, medial thalamus, and anterior cingulate cortex as well as the contralateral cerebellum. The distribution of the cortical evoked potentials was consistent with the locus of cortical activation observed with fMRI. CONCLUSION High-frequency stimulation via a lead placed in the anterior limb of the internal capsule induced widespread hemodynamic changes at both the cortical and subcortical levels including areas typically associated with the pathogenesis of obsessive-compulsive disorder.

Spectral signal space projection algorithm for frequency domain MEG and EEG denoising, whitening, and source imaging

MEG and EEG data contain additive correlated noise generated by environmental and physiological sources. To suppress this type of spatially coloured noise, source estimation is often performed with spatial whitening based on a measured or estimated noise covariance matrix. However, artifacts that span relatively small noise subspaces, such as cardiac, ocular, and muscle artifacts, are often explicitly removed by a variety of denoising methods (e.g., signal space projection) before source imaging. Here, we introduce a new approach, the spectral signal space projection (S(3)P) algorithm, in which time-frequency (TF)-specific spatial projectors are designed and applied to the noisy TF-transformed data, and whitened source estimation is performed in the TF domain. The approach can be used to derive spectral variants of all linear time domain whitened source estimation algorithms. The denoised sensor and source time series are obtained by the corresponding inverse TF-transform. The method is evaluated and compared with existing subspace projection and signal separation techniques using experimental data. Altogether, S(3)P provides an expanded framework for MEG/EEG data denoising and whitened source imaging in both the time and frequency/scale domains.