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Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: effects of variation in stimulation parameters.

OBJECTIVE: To investigate the relation between the variation of the parameters of stimulation and the clinical effectiveness in parkinsonian patients treated with deep brain stimulation of the subthalamic nucleus (STN), to provide information on the electrical parameter setting and the mechanism of action of deep brain stimulation. METHODS: Ten patients with Parkinson's disease bilaterally implanted in the STN were studied. For every patient the intensity of the stimulus necessary to obtain the disappearance of contralateral wrist rigidity (required clinical effect, RCE) and the side effect threshold in 20 different conditions of stimulation, coupling four pulse width values (60, 120, 210, 450 micros) with five rate values (10, 50, 90, 130, 170 Hz) were determined. All the patients were tested after a 12 hour withdrawal of antiparkinsonian drugs, and the clinical evaluation was double blind. RESULTS: In all the patients it was impossible to obtain the RCE using 10 and 50 Hz stimulus rates. For all the other stimulus rate values, the intensity-pulse width curves (IPWCs) for the RCE and for the side effect threshold showed a hyperbolic trend. For every pulse width value, increasing the rate from 90 to 130 and to 170 Hz progressively decreased the intensity of the stimulus necessary to reach the RCE, but the differences were not significant. Within the same rate value, the progressive reduction of the stimulus intensity necessary to obtain the RCE, obtained with the lengthening of the pulse width was significant (p<0.05) only comparing 60 with 210 micros and 60 with 450 micros. CONCLUSIONS: The findings give some useful indications for the electrical parameter setting in deep brain stimulation of the STN, and some information about the mechanism of action of deep brain stimulation.

Aged↗

Effect and time course of deep brain stimulation of the globus pallidus and subthalamus on motor features of Parkinson's disease.

We studied the effect and temporal profile of deep brain stimulation (DBS) of the globus pallidus and subthalamic nucleus on the motor signs of Parkinson's disease (PD). Four patients with bilateral deep brain stimulators of the globus pallidus and four patients with bilateral deep brain stimulators of the subthalamus were studied while taking no medication and at 15 and 30 minutes and 1, 2, 4, and 6 hours after turning stimulation on. An immediate (15 minutes) and sustained (6 hours) benefit was observed for all the motor manifestations of PD for both stimulation sites. Deep brain stimulation of the globus pallidus and subthalamus is highly effective in reducing all the cardinal motor features of PD.

Electric Stimulation Therapy↗

Deep brain stimulation in epilepsy.

Since the pioneering studies of Cooper et al. to influence epilepsy by cerebellar stimulation, numerous attempts have been made to reduce seizure frequency by stimulation of deep brain structures. Evidence from experimental animal studies suggests the existence of a nigral control of the epilepsy system. It is hypothesized that the dorsal midbrain anticonvulsant zone in the superior colliculi is under inhibitory control of efferents from the substantia nigra pars reticulata. Inhibition of the subthalamic nucleus (STN) could release the inhibitory effect of the substantia nigra pars reticulata on the dorsal midbrain anticonvulsant zone and thus activate the latter, raising the seizure threshold. Modulation of the seizure threshold by stimulation of deep brain structures-in particular, of the STN-is a promising future treatment option for patients with pharmacologically intractable epilepsy. Experimental studies supporting the existence of the nigral control of epilepsy system and preliminary results of STN stimulation in animals and humans are reviewed, and alternative mechanisms of seizure suppression by STN stimulation are discussed.

Animals↗

Chronic implantation of deep brain stimulation leads in animal models of neurological disorders.

Deep brain stimulation (DBS) has routinely been used as a treatment option in Parkinson's disease (PD), tremor disorders and, more recently, dystonia. Here, we describe a method of implantation of DBS leads in the monkey model of PD. By adapting procedures used in human patients, we have devised implantation techniques that can be readily applied to any animal model in which stimulation of subcortical structures is desired. The procedure for implantation consists of microelectrode mapping of the target structure, DBS lead preparation and implantation, and verification of lead placement. The stimulation system described in this paper allows for simultaneous recording of neuronal activity (during stimulation) and observation of animal behavior without restriction of the subject's head or body. In addition, we detail techniques for stimulation and recording from distant structures (utilizing either a one or two chamber system) to facilitate examination of the effects of DBS on neural activity. Thus, the correlation of changes in neuronal activity with behavior during stimulation of subcortical structures can be accomplished. In addition, the use of leads in primates which are analogous in size to human devices allows for close reproduction of the effects of stimulation as observed in humans.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Choice of Anesthesia in Microelectrode Recording-guided Deep Brain Stimulation Surgery for Parkinson's Disease (CHAMPION): A Noninferiority Randomized Controlled Trial.

BACKGROUND: Deep brain stimulation for Parkinson's disease is often performed under conscious sedation or general anesthesia. However, anesthetic agents may influence intraoperative microelectrode recording, and the optimal anesthesia method for microelectrode recording remains unclear. This study compared general anesthesia and conscious sedation in preserving microelectrode recording signal intensity during deep brain stimulation. METHODS: In this prospective, noninferiority randomized controlled trial, patients with Parkinson's disease (United Kingdom Brain Bank criteria) undergoing elective bilateral surgery were randomized 1:1 to the conscious sedation or the general anesthesia group. During surgery, a desflurane anesthetic titrated against the quality of the electrophysiologic signal was applied in the general anesthesia group, whereas patients in the conscious sedation group received dexmedetomidine anesthesia. The primary outcome was the proportion of patients with high-quality microelectrode recording (normalized root mean square greater than 2.0), assessed postoperatively off-line. Secondary outcomes included operation and recording duration, 6-month clinical efficacy, and complication rates. RESULTS: Of 188 randomized patients (94 general anesthesia, 93 conscious sedation), desflurane anesthesia was noninferior for high normalized root mean square proportion (89.4% vs . 90.3%; difference, -0.96%; 95% CI, -9.62 to 7.70). The general anesthesia group had shorter operative time (difference, -9.07&#x2009;min; 95% CI, -13.99 to -4.14; P < 0.001). At 6 months, changes in Unified Parkinson's Disease Rating Scale score (difference, -2.50; 95% CI, -7.20 to 2.20; P = 0.297), levodopa equivalent daily dose (difference, -58.4&#x2009;mg; 95% CI, -133.56 to 16.75; P = 0.128), and complication rates (general anesthesia: 10.9% vs . conscious sedation: 8.9%; P = 0.655) were comparable between the groups. CONCLUSIONS: General anesthesia is noninferior to conscious sedation for microelectrode-guided subthalamic nucleus deep brain stimulation, providing equivalent signal intensity and clinical outcomes while improving procedural efficiency, supporting its use as a valid clinical option.

Humans↗

Lower stimulation frequency can enhance tolerability and efficacy of pallidal deep brain stimulation for dystonia.

We report the case of a patient with medically refractory primary dystonia who was treated with bilateral pallidal deep brain stimulation. Stimulation at 130 Hz or higher, by means of the more ventral contacts generated capsular side effects, which made their use impractical. Consequently, the patient was treated for 9 months at 130 to 185 Hz, by means of the more dorsal contacts, achieving modest results. By reducing the stimulation frequency to 80 Hz, we were able to activate the ventral contacts without inducing side effects. Within days, the patient experienced a dramatic improvement in function that has persisted for 1 year. A further reduction in stimulation frequency to 60 Hz resulted in a worsening of his symptoms. We conclude that chronic stimulation at frequencies of <100 Hz may be efficacious in dystonia and may enhance the tolerability of stimulation by means of contacts that are positioned posteroventrally within the internal globus pallidus, nearer the internal capsule.

Deep Brain Stimulation↗

Split cannula method for accurate placement of an electrode for deep brain stimulation: technical note.

OBJECTIVE: We describe a "split cannula method" for accurate placement of a deep brain stimulation electrode. This method eliminates the risk of displacement of the electrode when withdrawing the outer guide cannula. METHOD: A separate short guide cannula is covered over the distal part of a long cannula for microrecording or macrostimulation. After confirmation of the stimulation point, the short cannula is fixed with an accessory-holding device and the long cannula is pulled out. The electrode for deep brain stimulation is inserted through the short cannula. Because this cannula is much shorter than the electrode, securing the stimulation electrode at any withdrawal stage of the outer guide cannula is always possible. RESULTS AND CONCLUSION: With this simple method, we experienced no displacement of the stimulation point during stereotactic insertion of a deep brain stimulation electrode. This method can be easily adapted to any stereotactic frame.

Brain↗

[Deep brain stimulation in the management of Parkinson's disease].

Deep brain stimulation (DBS) is a neurosurgical treatment of Parkinson's disease and other movement disorders. This surgical technique is applied to three brain targets: the ventral intermediate nucleus of the thalamus (Vim), the globus pallidus internus (Gpi) and the subthalamic nucleus (STN). Vim DBS improves contralateral parkinsonian tremor. STN and GPi DBS improve contralateral bradykinesia, rigidity, parkinsonian tremor and also levodopa-induced dyskinesia. There is little comparative data between bilateral STN and bilateral GPi procedures but the improvement with bilateral STN DBS seems more pronounced than with bilateral GPi DBS. Moreover, only STN BDS allows a significant decrease of antiparkinsonian medication. The other advantage of STN over GPi DBS is the lower consumption of current. The DBS procedure contrary to ablative surgery has the unique advantage of reversibility and adjustability over time. Patients with no behavioral, mood and cognitive impairments benefit the most from bilateral STN DBS. The stimulation-induced adverse effects related to DBS are reversible and adjustable. More specific adverse effects related do hardware are: disconnection, lead breaking, erosion or infection. The disadvantage of DBS is a relatively high cost. The setting of stimulation parameters to achieve the best clinical result may be very time-consuming. Most authors agree that DBS is a safer and more favorable procedure than ablative surgery.

Antiparkinson Agents↗

High frequency deep brain stimulation: what are the therapeutic mechanisms?

High frequency deep brain stimulation (HFS) used to treat the symptoms of Parkinson's disease (PD) was first assumed to act by reducing an excessive tonic GABAergic inhibitory output from the internal globus pallidus (GPi). Stimulation in GPi might produce this directly by mechanisms such as depolarization block or activation of presynaptic inhibitory fibers, and the same mechanisms evoked by HFS in the subthalamic nucleus (STN) could reduce the excitatory action of STN on GPi neurons. Although somatic recordings from neurons near the stimulation site may appear to support this potential mechanism, the action downstream from the site of stimulation often is not consistent with this interpretation. A more parsimonious explanation for the similar effects of HFS in STN or GPi and a lesion of either of these structures is that both HFS and pallidotomy interrupt an abnormal pattern of firing in cortico-basal ganglia-thalamocortical loops that is responsible for the symptoms of PD.

Cerebrovascular Circulation↗

Nursing time to program and assess deep brain stimulators in movement disorder patients.

The use of deep brain stimulation (DBS) to treat movement disorders such as Parkinson's disease, essential tremor, and dystonia is increasing. Although some published literature describes the methods for DBS programming, the time and nursing requirements to run a DBS surgical program have not been examined previously. For this study, we prospectively recorded the time required for both assessments and programming of the DBS from the preoperative period to 1 year after surgery in a variety of patients. Results showed that the mean total time spent programming the stimulator and assessing these patients ranged from 18.0-36.2 hours per patient. It took twice as long to program the stimulator in patients with Parkinson's disease as it did in patients with essential tremor or dystonia. When setting up a program for movement disorders surgery, nursing time spent on patient assessment and programming should be considered in the workload.

Activities of Daily Living↗

Deep-brain stimulation in a persistent vegetative state: follow-up results and criteria for selection of candidates.

Eight cases of a persistent vegetative state caused by brain damage were treated by chronic deep-brain stimulation (stimulation target: the mesencephalic reticular formation and/or non-specific thalamic nucleus) over a period of more than 6 months. Three of the patients are currently able to communicate and to express their demands by voice and one other patient has recovered very close to this state. These four cases showed changeable spectrograms with desynchronization on continuous EEG recording and all components of the BSR and SER could be recorded except for prolonged latency of both N20 (SER) and the V wave (BSR) 2 months after the initial coma. Following chronic deep-brain stimulation, EEG and behavioural arousal responses were observed with increased r-CBF, r-CMRO2 and r-CMRGL in the whole brain tissue. After 3-6 months of chronic deep brain stimulation, the prolonged coma scale rose in four of the eight cases and three cases emerged from the persistent vegetative state. Transmitter substances and their metabolites were also found to be increased in the CSF after chronic deep-brain stimulation. Based on these findings, chronic deep-brain stimulation represents a useful kind of treatment that can lead to emergence from a persistent vegetative state, if the candidate is selected by electrophysiological studies 2 months after the initial insult and if the stimulation is applied for more than 6-8 months using a high-safety chronic deep-brain stimulating instrument.

Adult↗

Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder.

Deep brain stimulation (DBS) of the anterior limb of the internal capsule has been shown to be beneficial in the short term for obsessive-compulsive disorder (OCD) patients who exhaust conventional therapies. Nuttin et al, who published the first DBS for OCD series, found promising results using a capsule target immediately rostral to the anterior commissure extending into adjacent ventral capsule/ventral striatum (VC/VS). Published long-term outcome data are limited to four patients. In this collaborative study, 10 adult OCD patients meeting stringent criteria for severity and treatment resistance had quadripolar stimulating leads implanted bilaterally in the VC/VS. DBS was activated openly 3 weeks later. Eight patients have been followed for at least 36 months. Group Yale-Brown Obsessive Compulsive Scale (YBOCS) scores decreased from 34.6+/-0.6 (mean+/-SEM) at baseline (severe) to 22.3+/-2.1 (moderate) at 36 months (p < 0.001). Four of eight patients had a > or =35% decrease in YBOCS severity at 36 months; in two patients, scores declined between 25 and 35%. Global Assessment of Functioning scores improved from 36.6+/-1.5 at baseline to 53.8+/-2.5 at 36 months (p < 0.001). Depression and anxiety also improved, as did self-care, independent living, and work, school, and social functioning. Surgical adverse effects included an asymptomatic hemorrhage, a single seizure, and a superficial infection. Psychiatric adverse effects included transient hypomanic symptoms, and worsened depression and OCD when DBS was interrupted by stimulator battery depletion. This open study found promising long-term effects of DBS in highly treatment-resistant OCD.

Adult↗

Long-term deep brain stimulation in elderly patients with cardiac pacemakers.

OBJECT: Deep brain stimulation (DBS) has become an accepted therapy for movement disorders such as Parkinson disease (PD) and essential tremor (ET), when these conditions are refractory to medical treatment. The presence of a cardiac pacemaker is still considered a contraindication for DBS in functional neurosurgery. The goal of this study was to evaluate the technical and clinical management of DBS for the treatment of movement disorders in elderly patients with cardiac pacemakers. METHODS: Six patients with cardiac pacemakers underwent clinical and cardiac examinations to analyze the safety of DBS in the treatment of movement disorders. Four patients suffered from advanced PD and two patients had ET. The mean age of these patients at surgery was 69.5 years (range 63-79 years). The settings of the pacemakers were programmed in a manner considered to minimize the chance of interference between the two systems. There were no adverse events during surgery. Four patients underwent stimulation of the thalamic ventralis intermedius nucleus (VIM), and two patients stimulation of the subthalamic nucleus. In general, bipolar sensing was chosen for the cardiac pacemakers. In all but one patient the quadripolar DBS electrodes were programmed for bipolar stimulation. Several control electrocardiography studies, including 24-hour monitoring, did not show any interference between the two systems. At the time this paper was written the patients had been followed up for a mean of 25.3 months (range 4-48 months). CONCLUSIONS: In certain conditions it is safe for patients with cardiac pacemakers to receive DBS for treatment of concomitant movement disorders. Cardiac pacemakers should not be viewed as a general contraindication for DBS in patients with movement disorders.

Aged↗

The effect of deep brain stimulation on quality of life in movement disorders.

Deep brain stimulation (DBS) is a viable treatment alternative for patients with Parkinson's disease (PD), essential tremor (ET), dystonia, and cerebellar outflow tremors. When poorly controlled, these disorders have detrimental effects on the patient's health related quality of life (HRQoL). Instruments that measure HRQoL are useful tools to assess burden of disease and the impact of therapeutic interventions on activities of daily living, employment, and other functions. We systematically and critically reviewed the literature on the effects of DBS on HRQoL in PD, ET, dystonia, and cerebellar outflow tremor related to multiple sclerosis.

Anxiety↗

Phacoemulsification in a patient with a deep brain stimulator.

We describe a 62-year-old man with a deep brain stimulator who had cataract surgery performed by phacoemulsification. Representatives of Medtronic and Alcon Laboratories would not sanction our proceeding with cataract surgery because of the possible interaction between the ultrasound and the device. Simulated cataract surgery 1 week before the scheduled operation failed to produce any consequences. One week later, the patient had uneventful cataract surgery. Although a single case does not guarantee the lack of interference between the ultrasound used in phacoemulsification and the deep brain stimulator, our safe outcome may warrant a place in the ophthalmic literature.

Deep Brain Stimulation↗

Deep brain stimulation in Parkinson's disease patients: biochemical evidence.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) patients augments STN-driven excitation of the internal globus pallidus (GPi). However, other DBS-induced changes are largely unknown. Here we report the biochemical effects of STN-DBS in two basal ganglia stations (putamen--PUT--and GPi) and in a thalamic relay nucleus, the anteroventral thalamus (VA). In six advanced PD patients undergoing surgery, microdialysis samples were collected from GPi, PUT and VA before, during and after one hour of STN-DBS. cGMP was measured in the GPi and PUT as an index of glutamatergic transmission, whereas GABA was measured in the VA. During clinically effective STN-DBS, we found a significant decrease in GABA extracellular concentrations in the VA (-25%). Simultaneously, cGMP extracellular concentrations were enhanced in the PUT (+200%) and GPi (+481%). DBS differentially affects fibers crossing the STN area: it activates the STN-GPi pathway while inhibiting the GPi-VA one. These findings support a thalamic dis-inhibition, as the main responsible for the clinical effect of STN-DBS. This, in turn, re-establishes a more physiological level of PUT activity.

Aged↗

Basic algorithms for the programming of deep brain stimulation in Parkinson's disease.

The clinical success of deep brain stimulation (DBS) for treating Parkinson's disease (PD) critically depends on the quality of postoperative neurological management. Movement disorder specialists becoming involved with this therapy need to acquire new skills to adapt optimally stimulation parameters and medication after implantation of a DBS system. At first glance, the infinite number of theoretically possible parameter combinations seems to make programming a complex and time-consuming art. This article outlines a stepwise and standardized approach, reducing the possible parameter settings in DBS to a few relevant combinations. The basic programming algorithms for thalamic, subthalamic, and pallidal stimulation in PD are explained and summarized in flowcharts.

Algorithms↗

Improvements in daily functioning after deep brain stimulation of the thalamus for intractable tremor.

Deep brain stimulation (DBS) of the thalamus reduces tremor in patients with essential tremor (ET). However, few studies have determined the degree of improvement in daily functioning associated with DBS. We developed a self-report Tremor Activities of Daily Living Scale (TADLS) to compare daily functioning with the stimulator turned on and off. Patients rated their performance on the 30 items of the TADLS with the stimulator turned off and then on. They also performed 10 activities under the supervision of a clinician who rated their functional ability with stimulation off and then on. There was a 58% improvement in self-rated TADLS scores in patients with DBS with the stimulator on compared with stimulation off. When activities were rated by the clinician, the average improvement in functioning with the stimulator on was 54%. There were reasonably high correlations between patient and clinician ratings of functioning. ET patients have a marked improvement in daily functioning with thalamic DBS.

Activities of Daily Living↗