Deep Brain Stimulation

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Jerzy Slowinski, Ryan J. Uitti, John D. Putzke and Robert E. Wharen Jr.

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Peter Novak, Slawomir Daniluk, Samuel A. Ellias and Jules M. Nazzaro

✓Accurate and fast localization of the subthalamic nucleus (STN) during intraoperative electrophysiological monitoring can improve the outcome of deep brain stimulation surgery. The authors show a simple method of detecting the STN that is based on an analysis of the high-frequency (> 500 Hz) background (HFB) activity of neurons. The HFB reflects multiunit spiking activity close to the recording electrode, and its characteristic profile, which is higher in the STN than in neighboring structures, and facilitates delineation of both the dorsal and ventral STN borders.

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Claudio Pollo, François Vingerhoets, Etienne Pralong, Joseph Ghika, Philippe Maeder, Reto Meuli, Jean-Philippe Thiran and Jean-Guy Villemure

Object

The authors describe a new method of localizing electrodes on magnetic resonance (MR) images and focus on the positions of both the most efficient contact and the electrode related to the MR imaging target.

Methods

Thirty-one patients who had undergone bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) were included in this study. Target coordinates were calculated in the anterior commissure–posterior commissure referential. A study of the correlation between the artifact and the related contact allowed one to deduce the contact position from the identification of the distal artifact on MR imaging. The best stimulation point corresponded with the contact resulting in the best Unified Parkinson’s Disease Rating Scale (UPDRS) motor score improvement. It was compared (Student t-test) with the dorsal margin of the STN (DM STN), which was determined electrophysiologically. The distance between the target and the electrode was calculated individually in each axis.

The best stimulation point was located at anteroposterior −2.34 ± 1.63 mm, lateral 12.04 ± 1.62 mm, and vertical −2.57 ± 1.68 mm. This point was not significantly different from the DM STN (p < 0.05). The postoperative UPDRS motor score was 28.07 ± 12.16, as opposed to the preoperative score of 46.27 ± 13.89. The distance between the expected and actual target in the x- and y-axes was 1.34 ± 1.02 and 1.03 ± 0.76 mm, respectively. In the z-axis, 39.7% of the distal contacts were located proximal to the target.

Conclusions

This approach proposed for the localization of the electrodes on MR imaging shows that DBS is most effective in the dorsal and lateral part of the STN and indicates that the DBS electrode can be located more proximally than originally expected because of the caudal brain shift that may occur during the implantation procedure.

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Dominique Guehl, Roderick Edwards, Emmanuel Cuny, Pierre Burbaud, Alain Rougier, Julien Modolo and Anne Beuter

Object

The subthalamic nucleus (STN) is currently recognized as the preferred target for deep brain stimulation (DBS) in patients with Parkinson disease (PD). If there is agreement in the literature that DBS improves motor symptoms significantly, the situation is less clear with respect to the side effects of this procedure. The goal of this study was to correlate the coordinate values of active electrode contacts with the amplitude of residual clinical symptoms and side effects using a mathematical approach.

Methods

In this study the investigators examined a cohort of 41 patients with PD who received clinical benefits from DBS after stimulating electrodes had been implanted bilaterally into the STN. The combined scores of residual clinical symptoms plus side effects, including speech disturbance, postural instability, and weight gain, were fitted by using either inverted ellipsoidal exponentials or smooth splines.

These analyses showed evidence of lower combined scores for stimulating contacts at an x coordinate approximately 12.0 to 12.3 mm lateral to the anterior commissure–posterior commissure (AC–PC) line and at a z coordinate approximately 3.1 to 3.3 mm under the AC–PC line. There was insufficient evidence for a preferred y coordinate location.

Conclusions

The authors propose a “best” therapeutic ellipse area that is centered at an x, z location of 12.5 mm, −3.3 mm and characterized by an extension of 1.85 mm in the x direction and 2.22 mm in the z direction. Therapeutic electrode contacts located within this area are well correlated with the lowest occurrence of residual symptoms and the lowest occurrence of side effects independent of STN anatomical considerations. The lack of a significant result in the y direction remains to be explored further.

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Dirk Rasche, Patricia C. Rinaldi, Ronald F. Young and Volker M. Tronnier

Object

Electrical intracerebral stimulation (also referred to as deep brain stimulation [DBS]) is a tool for the treatment of chronic pain states that do not respond to less invasive or conservative treatment options. Careful patient selection, accurate target localization, and identification with intraoperative neurophysiological techniques and blinded test evaluation are the key requirements for success and good long-term results. The authors present their experience with DBS for the treatment of various chronic pain syndromes.

Methods

In this study 56 patients with different forms of neuropathic and mixed nociceptive/neuropathic pain syndromes were treated with DBS according to a rigorous protocol. The postoperative follow-up duration ranged from 1 to 8 years, with a mean of 3.5 years. Electrodes were implanted in the somatosensory thalamus and the periventricular gray region. Before implantation of the stimulation device, a double-blinded evaluation was carefully performed to test the effect of each electrode on its own as well as combined stimulation with different parameter settings.

The best long-term results were attained in patients with chronic low-back and leg pain, for example, in so-called failed–back surgery syndrome. Patients with neuropathic pain of peripheral origin (such as complex regional pain syndrome Type II) also responded well to DBS. Disappointing results were documented in patients with central pain syndromes, such as pain due to spinal cord injury and poststroke pain. Possible reasons for the therapeutic failures are discussed; these include central reorganization and neuroplastic changes of the pain-transmitting pathways and pain modulation centers after brain and spinal cord lesions.

Conclusions

The authors found that, in carefully selected patients with chronic pain syndromes, DBS can be helpful and can add to the quality of life.

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Robert J. Coffey and Andres M. Lozano

Object

Neurostimulation to treat chronic pain includes approved and investigational therapies directed at the spinal cord, thalamus, periaqueductal or periventricular gray matter, motor cortex, and peripheral nerves. Persistent pain after surgery and work-related or neural injuries are common indications for such treatments. In light of the risks, efforts, costs, and expectations associated with neurostimulation therapies, a careful reexamination of the methods used to gather evidence for this treatment’s long-term efficacy is in order.

Methods

The authors combed English-language publications to determine the nature of the evidence supporting the efficacy of neurostimulation therapies for chronic noncancer pain. To formulate recommendations for the design of future studies, the results of their analysis were compared with established guidelines for the evaluation of medical evidence.

Evidence supporting the efficacy of neurostimulation has been collected predominantly from retrospective series or from prospective studies whose design or methods of analysis make them subject to limited interpretation. To date, there has been no successful clinical study focused on establishing the efficacy of neurostimulation for pain and incorporating sufficient numbers of participants, matched control groups, sham stimulation, randomization, prospectively defined end points, and methods for controlling experimental bias. Currently available data provide little support for the common practices of psychological or pharmacological screening or trial stimulation to predict and/or improve long-term results.

Conclusions

These findings do not diminish the value of previous investigations or positive patient experiences and do not mean that the treatments are ineffective; rather, they reveal that new data are required to answer the questions raised in and by previous study data. Future analyses of emerging neurostimulation modalities for pain should, whenever feasible, require unambiguous diagnoses as an entry criterion and should involve the use of randomization, parallel control groups that receive sham stimulation, and blinding of patients, investigators, and device programmers. Given the chronicity of patient symptoms and stimulation therapies, efficacy should be studied for 1 year or longer after device implantation. Meticulous study methods are especially important to evaluate new therapies like motor cortex and occipital nerve stimulation.

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Shouyan Wang, Xuguang Liu, John Yianni, Alex L. Green, Carole Joint, John F. Stein, Peter G. Bain, Ralph Gregory and Tipu Z. Aziz

Object

The object of this study was to identify a preoperative physiological index by using surface electromyography (EMG) signals that would correlate with clinical outcome in dystonic patients following bilateral pallidal stimulation.

Methods

In 14 patients with spasmodic torticollis, generalized dystonia, and myoclonic dystonia, surface EMG signals were recorded from the most affected muscle groups. Although the dystonia affected different body segments, the EMG signals in all patients could be decomposed into bursting and sustained components. Subsequently, a ratio of the EMG amplitude was calculated between the two components and then correlated with clinical outcome.

Patients who experienced rapid improvement following bilateral pallidal stimulation had a significantly higher EMG ratio compared with those who did not. Furthermore, a significant correlation was found between the EMG ratio and clinical improvement during the 12-month period following pallidal stimulation.

Conclusions

The authors concluded that surface EMG studies could be used to predict the clinical outcome of and to select patients for pallidal stimulation for dystonia.

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Patrick B. Senatus, David Teeple, Shearwood McClelland III, Seth L. Pullman, Qiping Yu, Blair Ford, Guy M. McKhann II and Robert R. Goodman

Object

Implantation of a subthalamic nucleus (STN) deep brain stimulation (DBS) electrode is increasingly recognized as an effective treatment for advanced Parkinson disease (PD). Despite widespread use of microelectrode recording (MER) to delineate the boundaries of the STN prior to stimulator implantation, it remains unclear to what extent MER improves the clinical efficacy of this procedure. In this report, the authors analyze a series of patients who were treated at one surgical center to determine to what degree final electrode placement was altered, based on readings obtained with MER, from the calculated anatomical target.

Methods

Subthalamic DBS devices were placed bilaterally in nine patients with advanced PD. Frame-based volumetric magnetic resonance images were acquired and then transferred to a stereotactic workstation to determine the anterior and posterior commissure coordinates and plane. The initial anatomical target was 4 mm anterior, 4 mm deep, and 12 mm lateral to the midcommissural point. The MERs defined the STN boundaries along one or more parallel tracks, refining the final electrode placement by comparison of results with illustrations in a stereotactic atlas.

In eight of 18 electrodes, the MER results did not prompt an alteration in the anatomically derived target. In another eight placements, MER altered the target by less than 1 mm and two of 18 electrode positions differed by less than 2 mm. The anterior–posterior difference was 0.53 ± 0.65 mm, whereas the medial–lateral direction differed by 0.25 ± 0.43 mm. The ventral boundary of the STN defined by MER was 2 ± 0.72 mm below the calculated target (all values are the means ± standard deviation). All patients attained clinical improvement, similar to previous reports.

Conclusions

In this series of patients, microelectrode mapping of the STN altered the anatomically based target only slightly. Because it is not clear whether such minor adjustments improve clinical efficacy, a prospective clinical comparison of MER-refined and anatomical targeting may be warranted.

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Kelly E. Lyons and Rajesh Pahwa

Object

The aim of this study was to assess the long-term effects of bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson disease (PD) on sleep, daytime sleepiness, and early morning dystonia and to evaluate the relationship between total sleep time and motor function.

Methods

Patients who had undergone bilateral STN DBS and a follow-up evaluation of 6 months (89 patients), 12 months (83 patients), and 24 months (43 patients) were included in this study. The patients were preoperatively assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) in the medication-on and -off conditions, and they completed patient diaries. A subset of patients also completed the Epworth Sleepiness Scale. These assessments were repeated postoperatively with stimulation.

The UPDRS activities of daily living (ADL) and motor scores as well as total sleep hours were significantly improved at 6, 12, and 24 months poststimulation and with no medication compared with baseline values. Increased sleep time was significantly correlated with improvements in bradykinesia but not with tremor or rigidity. Patient-reported sleep problems and early morning dystonia were reduced after STN DBS. Antiparkinsonian medications were significantly reduced after STN DBS; however, there were no changes in excessive daytime sleepiness 6, 12, or 24 months after surgery.

Conclusions

Bilateral STN DBS increased total sleep time and reduced patient-reported sleep problems and early morning dystonia for up to 24 months posttreatment. These changes in sleep were related to improvements in functioning, specifically those affected by bradykinesia. Despite significant reductions in antiparkinsonian medications, STN DBS did not reduce excessive daytime sleepiness.

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Rajesh Pahwa, Kelly E. Lyons, Steven B. Wilkinson, Richard K. Simpson Jr., William G. Ondo, Daniel Tarsy, Thorkild Norregaard, Jean P. Hubble, Donald A. Smith, Robert A. Hauser and Joseph Jankovic

Object

The effects of thalamic deep brain stimulation (DBS) on essential tremor (ET) and Parkinson disease (PD) have been well documented, but there is a paucity of long-term data. The aim of this study was to evaluate the longterm safety and efficacy of DBS of the ventralis intermedius nucleus (VIM) of the thalamus for PD and ET.

Methods

Thirty-eight of 45 patients enrolled at five sites completed a 5-year follow-up study. There were 26 patients with ET and 19 with PD undergoing 29 unilateral (18 ET/11 PD) and 16 bilateral (eight ET/eight PD) procedures. Patients with ET were evaluated using the Tremor Rating Scale, and patients with PD were evaluated using the Unified Parkinson’s Disease Rating Scale. The mean age of patients with ET was 70.2 years and 66.3 years in patients with PD. Unilaterally implanted patients with ET had a 75% improvement of the targeted hand tremor; those with bilateral implants had a 65% improvement in the left hand and 86% in the right compared with baseline. Parkinsonian patients with unilateral implants had an 85% improvement in the targeted hand tremor and those with bilateral implants had a 100% improvement in the left hand and 90% improvement in the right. Common DBS-related adverse events in patients receiving unilateral implants were paresthesia (45%) and pain (41%), and in patients receiving implants bilaterally dysarthria (75%) and balance difficulties (56%) occurred. Device-related surgical revisions other than IPG replacements occurred in 12 (27%) of the 45 patients.

Conclusions

Thalamic stimulation is safe and effective for the long-term management of essential and parkinsonian tremors. Bilateral stimulation can cause dysarthria and incoordination and should be used cautiously.