Deep Brain Stimulation

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Jeffrey E. Arle, Diana Apetauerova, Janet Zani, D. Vedran Deletis, Dana L. Penney, Daniel Hoit, Christine Gould and Jay L. Shils

Object

Since the initial 1991 report by Tsubokawa et al., stimulation of the M1 region of cortex has been used to treat chronic pain conditions and a variety of movement disorders.

Methods

A Medline search of the literature published between 1991 and the beginning of 2007 revealed 459 cases in which motor cortex stimulation (MCS) was used. Of these, 72 were related to a movement disorder. More recently, up to 16 patients specifically with Parkinson disease were treated with MCS, and a variety of results were reported. In this report the authors describe 4 patients who were treated with extradural MCS.

Results

Although there were benefits seen within the first 6 months in Unified Parkinson's Disease Rating Scale Part III scores (decreased by 60%), tremor was only modestly managed with MCS in this group, and most benefits seen initially were lost by the end of 12 months.

Conclusions

Although there have been some positive findings using MCS for Parkinson disease, a larger study may be needed to better determine if it should be pursued as an alternative surgical treatment to DBS.

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Bianca M. L. Stelten, Lieke H. M. Noblesse, Linda Ackermans, Yasin Temel and Veerle Visser-Vandewalle

Addiction or substance dependence is a psychiatric disorder that affects many individuals in the general population. Different theories concerning the neurobiological aspects of addiction have been proposed. Special attention has been paid to models concerning dysregulation of the reward circuit and the inhibitory control system within the cortico-basal ganglia-thalamocortical pathways. In the past, attempts have been made to treat patients suffering from addiction by performing psychosurgery. Lesions were created in specific brain regions that were believed to be dysfunctional in addiction. Procedures such as cingulotomy, hypothalamotomy, and resection of the substantia innominata and the nucleus accumbens have been described as a treatment for severe addictive disorders. Deep brain stimulation, a neurosurgical treatment that has been proven to be a safe alternative for lesions in the treatment of movement disorders, has more recently been proposed as treatments for severe psychiatric conditions such as treatment-refractory obsessive-compulsive disorder and depression. With the expanding knowledge of the neurobiology of addiction, deep brain stimulation could be a future option in the treatment arsenal of addiction.

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Jason S. Hauptman, Antonio A. F. DeSalles, Randall Espinoza, Mark Sedrak and Warren Ishida

Object

The goal of this study was to evaluate the definition of treatment-resistant depression (TRD), review the literature regarding deep brain stimulation (DBS) for TRD, and identify potential anatomical and functional targets for future widespread clinical application.

Methods

A comprehensive literature review was performed to determine the current status of DBS for TRD, with an emphasis on the scientific support for various implantation sites.

Results

The definition of TRD is presented, as is its management scheme. The rationale behind using DBS for depression is reviewed. Five potential targets have been identified in the literature: ventral striatum/nucleus accumbens, subgenual cingulate cortex (area 25), inferior thalamic peduncle, rostral cingulate cortex (area 24a), and lateral habenula. Deep brain stimulation electrodes thus far have been implanted and activated in only the first 3 of these structures in humans. These targets have proven to be safe and effective, albeit in a small number of cases.

Conclusions

Surgical intervention for TRD in the form of DBS is emerging as a viable treatment alternative to existing modalities. Although the studies reported thus far have small sample sizes, the results appear to be promising. Various surgical targets, such as the subgenual cingulate cortex, inferior thalamic peduncle, and nucleus accumbens, have been shown to be safe and to lead to beneficial effects with various stimulation parameters. Further studies with larger patient groups are required to adequately assess the safety and efficacy of these targets, as well as the optimal stimulation parameters and long-term effects.

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Hideki Oshima, Yoichi Katayama, Chikashi Fukaya, Toshikazu Kano, Kazutaka Kobayashi, Takamitsu Yamamoto and Yutaka Suzuki

✓Beginning-of-dose motor deterioration (BDMD) is a complication of levodopa medications in Parkinson disease (PD) that is presumably caused by inhibitory effects of levodopa. Only limited experience of BDMD has been described in the literature. The authors report the case of a patient with PD who demonstrated a marked BDMD while being treated with standard levodopa medications. This 55-year-old woman had a 12-year history of PD and a 10-year history of levodopa treatment. Marked exacerbation of symptoms occurred 15 to 20 minutes after every dose of levodopa at 100 mg and lasted approximately 15 minutes. The PD symptoms, particularly tremor and rigidity, were exacerbated more markedly during this period than during the wearing-off deterioration. The BDMD could be controlled very well by subthalamic nucleus (STN) stimulation without any change in the regimen of levodopa medications. These observations suggest that the BDMD was inhibited by STN stimulation through a direct effect.

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Hiroki Toda, Clement Hamani, Adrian P. Fawcett, William D. Hutchison and Andres M. Lozano

Object

To examine the influence of deep brain stimulation on hippocampal neurogenesis in an adult rodent model.

Methods

Rats were anesthetized and treated for 1 hour with electrical stimulation of the anterior nucleus of the thalamus (AN) or sham surgery. The animals were injected with 5′-bromo-2′-deoxyuridine (BrdU) 1–7 days after surgery and killed 24 hours or 28 days later. The authors counted the BrdU-positive cells in the dentate gyrus (DG) of the hippocampus. To investigate the fate of these cells, they also stained sections for doublecortin, NeuN, and GFAP and analyzed the results with confocal microscopy. In a second set of experiments they assessed the number of DG BrdU-positive cells in animals treated with corticosterone (a known suppressor of hippocampal neurogenesis) and sham surgery, corticosterone and AN stimulation, or vehicle and sham surgery.

Results

Animals receiving AN high-frequency stimulation (2.5 V, 90 μsec, 130 Hz) had a 2- to 3-fold increase in the number of DG BrdU-positive cells compared with nonstimulated controls. This increase was not seen with stimulation at 10 Hz. Most BrdU-positive cells assumed a neuronal cell fate. As expected, treatment with corticosterone significantly reduced the number of DG BrdU-positive cells. This steroid-induced reduction of neurogenesis was reversed by AN stimulation.

Conclusions

High-frequency stimulation of the AN increases the hippocampal neurogenesis and restores experimentally suppressed neurogenesis. Interventions that increase hippocampal neurogenesis have been associated with enhanced behavioral performance. In this context, it may be possible to use electrical stimulation to treat conditions associated with impairment of hippocampal function.

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Yasushi Miyagi, Fumio Shima and Tomio Sasaki

Object

The goal of this study was to focus on the tendency of brain shift during stereotactic neurosurgery and the shift's impact on the unilateral and bilateral implantation of electrodes for deep brain stimulation (DBS).

Methods

Eight unilateral and 10 bilateral DBS electrodes at 10 nuclei ventrales intermedii and 18 subthalamic nuclei were implanted in patients at Kaizuka Hospital with the aid of magnetic resonance (MR) imaging–guided and microelectrode-guided methods. Brain shift was assessed as changes in the 3D coordinates of the anterior and posterior commissures (AC and PC) with MR images before and immediately after the implantation surgery. The positions of the implanted electrodes, based on the midcommissural point and AC–PC line, were measured both on x-ray films (virtual position) during surgery and the postoperative MR images (actual position) obtained on the 7th day postoperatively.

Results

Contralateral and posterior shift of the AC and PC were the characteristics of unilateral and bilateral procedures, respectively. The authors suggest the following. 1) The first unilateral procedure elicits a unilateral air invasion, resulting in a contralateral brain shift. 2) During the second procedure in the bilateral surgery, the contralateral shift is reset to the midline and, at the same time, the anteroposterior support by the contralateral hemisphere against gravity is lost due to a bilateral air invasion, resulting in a significant posterior (caudal) shift.

Conclusions

To note the tendency of the brain to shift is very important for accurate implantation of a DBS electrode or high frequency thermocoagulation, as well as for the prediction of therapeutic and adverse effects of stereotactic surgery.

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W. Jeffrey Elias, Kai-Ming Fu and Robert C. Frysinger

Object

The success of stereotactic surgery depends upon accuracy. Tissue deformation, or brain shift, can result in clinically significant errors. The authors measured cortical and subcortical brain shift during stereotactic surgery and assessed several variables that may affect it.

Methods

Preoperative and postoperative magnetic resonance imaging volumes were fused and 3D vectors of deviation were calculated for the anterior commissure (AC), posterior commissure (PC), and frontal cortex. Potential preoperative (age, diagnosis, and ventricular volume), intraoperative (stereotactic target, penetration of ventricles, and duration of surgery), and postoperative (volume of pneumocephalus) variables were analyzed and correlated with cortical (frontal cortex) and subcortical (AC, PC) deviations.

Results

Of 66 cases, nine showed a shift of the AC by more than 1.5 mm, and five by more than 2.0 mm. The largest AC shift was 5.67 mm. Deviation in the x, y, and z dimensions for each case was determined, and most of the cortical and subcortical shift occurred in the posterior direction. The mean 3D vector deviations for frontal cortex, AC, and PC were 3.5 ± 2.0, 1.0 ± 0.8, and 0.7 ± 0.5 mm, respectively. The mean change in AC–PC length was −0.2 ± −0.9 mm (range −4.28 to 1.66 mm). The volume of postoperative pneumocephalus, assumed to represent cerebrospinal fluid (CSF) loss, was significantly correlated with shift of the frontal cortex (r = 0.640, 64 degrees of freedom, p < 0.001) and even more strongly with shift of the AC (r = 0.754, p < 0.001). No other factors were significantly correlated with AC shift. Interestingly, penetration of the ventricles during electrode insertion, whether unilateral or bilateral, did not affect volume of pneumocephalus.

Conclusions

Cortical and subcortical brain shift occurs during stereotactic surgery as a direct function of the volume of pneumocephalus, which probably reflects the volume of CSF that is lost. Clinically significant shifts appear to be uncommon, but stereotactic surgeons should be vigilant in preventing CSF loss.

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Sylvie Raoul, Dominique Leduc, Thomas Vegas, Paul Sauleau, Andres M. Lozano, Marc Vérin, Philippe Damier and Youenn Lajat

Object

Deep brain stimulation (DBS) has been shown to be an effective treatment for various types of movement disorders. High-frequency stimulation is applied to specific brain targets through an implanted quadripolar lead connected to a pulse generator. These leads can be used for creating lesions in the brain. The experimental study reported here was designed to examine the electrical parameters that could be used to create reproducible therapeutic lesions in the brain.

Methods

Egg whites were used to measure the relationship between the electrical parameters (current and voltage) applied through the DBS electrode and the size of coagulum. The authors measured current spread from the electrode contact used for lesioning to the adjacent contact. Similar studies were performed in the pallidum or the thalamus of human cadavers. Modeling of the lesion size was performed with simulation of current density and temperature. The ultrastructure of the electrodes after lesioning was verified by electron microscopy.

Results

Coagulation size increased with time but reached a plateau after 30 seconds. For a given set of electrical parameters, reproducibility of the size of lesions was high. Using constant voltage, lesions were larger in egg whites than in cadaveric brains with a mean length of 5 ± 0.6 mm in egg whites at 40 V, 125 mA, impedance 233 Ω; and 4.0 ± 0.8 mm in cadavers at 40 V, 38 mA, impedance 1333 Ω. Computer modeling indicated negligible current flow to the adjacent, unused electrodes. The electrodes showed no structural alterations on scanning electron microscopy after more than 200 lesions.

Conclusions

Results of this study demonstrate that DBS electrodes can be used to generate lesions reproducibly in the brain. The choice of lesioning parameters must take into account differences in impedance between the test medium (egg whites) and the human brain parenchyma.

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Alan Diamond, Christopher Kenney, Michael Almaguer and Joseph Jankovic

✓The authors present a unique case of hyperhidrosis as a side effect of a misplaced deep brain stimulation (DBS) electrode near the ventrointermedius (Vim) nucleus in a patient with essential tremor. Magnetic resonance imaging of the brain showed electrode placement in the left anterior thalamus traversing the hypothalamus. High-frequency electrical stimulation possibly resulted in unilateral activation of the efferent sympathetic pathways in the zona incerta. Although a rare complication, hypothalamic dysfunction may occur as a stimulation-related side effect of Vim-DBS.

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Charles A. Sansur, Robert C. Frysinger, Nader Pouratian, Kai-Ming Fu, Markus Bittl, Rod J. Oskouian, Edward R. Laws and W. Jeffrey Elias

Object

Intracranial hemorrhage (ICH) is the most significant complication associated with the placement of stereotactic intracerebral electrodes. Previous reports have suggested that hypertension and the use of microelectrode recording (MER) are risk factors for cerebral hemorrhage. The authors evaluated the incidence of symptomatic ICH in a large cohort of patients with various diseases treated with stereotactic electrode placement. They examined the effect of comorbidities on the risk of ICH and independently assessed the risks associated with age, sex, use of MER, diagnosis, target location, hypertension, and previous use of anticoagulant medications. The authors also evaluated the effect of hemorrhage on length of hospital stay and discharge disposition.

Methods

Between 1991 and 2005, 567 electrodes were placed by two neurosurgeons during 337 procedures in 259 patients. Deep brain stimulation (DBS) was performed in 167 procedures, radiofrequency lesioning (RFL) of subcortical structures in 74, and depth electrodes were used in 96 procedures in patients with epilepsy. Electrodes were grouped according to target, patient diagnosis, use of MER, patient history of hypertension, and patient prior use of anticoagulant medication (stopped 10 days before surgery). The Charlson Comorbidity Index (CCI) was used to evaluate the effect of comorbidities. The CCI score, patient age, length of hospital stay, and discharge status were continuous variables. Symptomatic hemorrhages were grouped as transient or leading to permanent neurological deficits.

Results

The risk of hemorrhage leading to permanent neurological deficits in this study was 0.7%, and the risk of symptomatic hemorrhage was 1.2%. A patient history of hypertension was the most significant factor associated with hemorrhage (p = 0.007). Older age, male sex, and a diagnosis of Parkinson disease (PD) were also significantly associated with hemorrhage (p = 0.01, 0.04, 0.007, respectively). High CCI scores, specific target locations, and prior use of anticoagulant therapy were not associated with an increased risk of hemorrhage. The use of MER was not found to be correlated with an increased hemorrhage rate (p = 0.34); however, the number of hemorrhages in the patients who underwent DBS was insufficient to draw definitive conclusions. The mean length of stay for the DBS, RFL, and depth electrode patient groups was 2.9, 2.6, and 11.0 days, respectively. For patients who received DBS and RFL, the mean duration of hospitalization in cases of symptomatic hemorrhage was 8.2 days compared with 2.7 days in those without hemorrhaging (p < 0.0001). Three of the seven patients with symptomatic hemorrhages were discharged home.

Conclusions

The placement of stereotactic electrodes is generally safe, with a symptomatic hemorrhage rate of 1.2%, and a 0.7% rate of permanent neurological deficit. Consistent with prior reports, this study confirms that hypertension is a significant risk factor for hemorrhage. Age, male sex, and diagnosis of PD were also significant risk factors. Patients with symptomatic hemorrhage had longer hospital stays and were less likely to be discharged home.