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A quick and universal method for stereotactic visualization of the subthalamic nucleus before and after implantation of deep brain stimulation electrodes.

For deep brain stimulation (DBS) of the subthalamic nucleus (STN), it would be an advantage if the STN could be visualized with fast acquisition of MR images, allowing direct and individual targeting. We present a protocol for T2-weighted, nonvolumetric fast-acquisition MRI, implemented at 8 centers in 6 countries. Acquisition time varied between 3 min 5 s and 7 min 48 s according to the center, and imaging often provided visualization of the STN on axial and coronal scans. Postoperatively, the same imaging protocol permitted visualization of the target area and DBS electrodes with minimum artifacts. This imaging technique may contribute to a decrease in the number of electrode passes at surgery.

Electric Stimulation Therapy↗

Pseudo-bilateral hand motor responses evoked by transcranial magnetic stimulation in patients with deep brain stimulators.

OBJECTIVES: In 3 of 5 patients with dystonia and bilaterally implanted deep brain stimulating electrodes, focal transcranial magnetic stimulation (TMS) of one motor cortex elicited bilateral hand motor responses. The aim of this study was to clarify the origin of these ipsilateral responses. METHODS: TMS and electrical stimulation of corticospinal fibres by the implanted electrodes were performed and the evoked hand motor potentials were analysed. RESULTS: In comparison with responses elicited by contralateral motor cortex stimulation, ipsilateral responses were smaller in amplitude (3.0+/-1.4 versus 5.8+/-1.5 mV), had shorter peak latencies (first negative peak: 20.9+/-0.8 versus 25.1+/-0.4 ms) and were followed by a shorter-lasting silent period (46+/-4 versus 195+/-35 ms). Ipsilateral responses following TMS had similar peak latencies to responses elicited subcortically by deep brain stimulation (DBS) (20.4+/-0.9 ms). CONCLUSIONS: Hand motor responses ipsilateral to TMS result from a subcortical activation of corticospinal fibres, via the implanted electrode in the other hemisphere, secondary to currents induced by TMS in subcutaneous wire loops that underlie the magnetic coil. Studies of TMS in patients with DBS have to take this potential source of confounding into account.

Adolescent↗

Risk factors for unpleasant paresthesiae induced by paresthesiae-producing deep brain stimulation.

Paresthesiae-producing deep brain stimulation (stimulation of ventrocaudal nucleus-VC, medial lemniscus-ML or internal capsule-IC) is one of the few procedures to treat the steady element of neural injury pain (NIP) currently available. Reviewing the first 60 patients with NIP submitted to deep brain stimulation (DBS) from 1978 to 1991 at the Division of Neurosurgery, Toronto Hospital, University of Toronto, we observed that 6 patients complained of unpleasant paresthesiae with paresthesiae-producing DBS, preventing permanent electrode implantation in all of them. Such patients accounted for 15% of the failures (6 out of 40 failures) in our series. In an attempt to improve patient selection, we reviewed our patients considering a number of parameters in order to determine risk factors for unpleasant paresthesiae elicited by paresthesiae-producing DBS. The results showed that this response happened only in patients with brain central pain complaining of evoked pain, secondary to a supratentorial lesion. Age, sex, duration of pain, quality of the steady pain, size of the causative lesion and site (VC,ML,IC) and type (micro or macroelectrode) of surgical exploration were not important factors. Unpleasant parethesiae in response to dorsal column stimulation, restricted thalamic lesion on computed tomography and the occurrence of associated intermittent pain were considered major risk factors in this subset of patients and the presence of cold allodynia or hyperpathia in isolation and the absence of sensory loss were considered minor risk factors. It is our hope that the criteria here established will improve patient selection and so, the overall results of DBS.

Adult↗

Deep brain stimulation creates an informational lesion of the stimulated nucleus.

Deep brain stimulation (DBS) is an effective treatment for movement disorders, but the mechanisms are unclear. DBS generates inhibition of neurons surrounding the electrode while simultaneously activating the output axons of local neurons. This dual effect does not explain two hallmarks of DBS effectiveness: symptom relief is dependent on using a sufficiently high-stimulation frequency, and clinical effects are analogous to those produced by lesion. The effect of DBS at different frequencies on the output of intrinsically active neurons was studied using computational models. DBS produced frequency-dependent modulation of the variability of neuronal output, and above a critical frequency stimulation resulted in regular output with zero variance. The resulting loss of information offers an explanation for the two hallmarks of DBS effectiveness.

Electric Stimulation Therapy↗

Most effective stimulation site in subthalamic deep brain stimulation for Parkinson's disease.

The optimal stimulation site in subthalamic deep brain stimulation (STN-DBS) was evaluated by correlation of the stereotactic position of the stimulation electrode with the electrophysiologically specified dorsal STN border. In a series of 25 electrodes, best clinical results with least energy consumption were found in contacts located in the dorsolateral border zone, whereas contacts within the subthalamic white matter, e.g., zona incerta, were significantly less effective. We suggest that the dorsolateral STN border should be covered by STN-DBS.

Electric Stimulation Therapy↗

Choosing electrodes for deep brain stimulation experiments--electrochemical considerations.

Deep brain stimulation (DBS) is a therapy of movement disorders including Parkinson's disease (PD). Commercially available electrodes for animal models of Parkinson's disease vary in geometry and material. We characterized such electrodes and found a drift in their properties within minutes and up to about 60 h after immersion in cell culture medium, both with and without a stimulation signal. Electrode properties could largely be restored by proteolytic treatment for platinum/iridium electrodes but not for stainless steel ones. Short-term drift and irreversible aging could be followed by impedance measurements. Aging was accompanied by metal corrosion and erosion of the plastic insulation. For both materials, the degradation rates depended on the current density at the electrode surfaces. Fourier analysis of the DBS pulse (60 micros, repetition rate 130 Hz) revealed harmonic frequencies spanning a band of more than three decades, with significant harmonics up to the MHz range. The band is located in a window imposed by electrode processes and capacitive cell membrane bridging at the low and high frequency ends, respectively. Even though electrode processes are reduced at higher frequencies they only vanish above 1 MHz and cannot be avoided. Therefore, the use of inert electrode materials is of special importance. The neurotoxicity of iron makes avoiding stainless steel electrodes imperative. Future developments need to avoid the use of corrosive materials and current density hot spots at the electrode surface, and to reduce low frequency components in the DBS pulses in order to diminish electrode processes.

Brain↗

Clinical response to varying the stimulus parameters in deep brain stimulation for essential tremor.

Deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus for essential tremor is sometimes limited by side effects. The mechanisms by which DBS alleviates tremor or causes side effects are unclear; thus, it is difficult to select stimulus parameters that maximize the width of the therapeutic window. The goal of this study was to quantify the impact on side effect intensity (SE), tremor amplitude, and the therapeutic window of varying stimulus parameters. Tremor amplitude and SE were recorded at 40 to 90 combinations of pulse width, frequency, and voltage across 14 thalami. Posterior variable inclusion probabilities indicated that frequency and voltage were the most important predictors of both SE and tremor amplitude. The amount of tremor suppression achieved at frequencies of 90 to 100 Hz was not different from that at 160 to 170 Hz. However, the width of the therapeutic window decreased significantly and power consumption increased as frequency was increased above 90 to 100 Hz. Improved understanding of the relationships between stimulus parameters and clinical responses may lead to improved techniques of stimulus parameter adjustment.

Adult↗

Deep brain stimulation in neurologic disorders.

Deep brain stimulation (DBS) is an effective surgical therapy for well-selected patients with medically intractable Parkinson's disease (PD) and essential tremor (ET). The purpose of this review is to describe the success of DBS in these two disorders and its promising application in dystonia, Tourette Syndrome (TS) and epilepsy. In the last 10 years, numerous short- and intermediate-term outcome studies have demonstrated significant relief to patients with PD and ET. A few long-term follow-up studies have also reported sustained benefits. When successful, DBS greatly reduces most of parkinsonian motor symptoms and drug-induced dyskinesia, and it frequently improves patients' ability to perform activities of daily living with less encumbrance from motor fluctuations. Quality of life is enhanced and many patients are able to significantly reduce the amount of antiparkinsonian medications required to still get good pharmacological benefit. Overall, adverse effects associated with DBS tend to be transient, although device-related and other postoperative complications do occur. DBS should be considered the surgical procedure of choice for patients who meet strict criteria with medically intractable PD, ET and selected cases of dystonia.

Clinical Trials as Topic↗

Neuronal response to local electrical stimulation in rat thalamus: physiological implications for mechanisms of deep brain stimulation.

High-frequency deep brain stimulation (DBS) of sensorimotor thalamus containing "tremor cells" leads to tremor arrest in humans with parkinsonian and essential tremor. To examine the possible underlying mechanism(s), we recorded in vitro intracellular responses of rat thalamic neurons to local intrathalamic stimulation. Such simulated DBS (sDBS) induced a sustained membrane depolarization accompanied by an increase in apparent membrane conductance in both motor and sensory neurons. With stimulation frequency above approximately 100 Hz, the sDBS-induced depolarization most typically led to repetitive neuronal firing or less frequently resulted in a complete blockade of action potential genesis. When regular intracellular current pulses were injected into cells to mimic "tremor" activity, such rhythmic discharges were invariably disrupted or abolished by the random spike firing induced during high-frequency sDBS. Low-frequency sDBS left rhythmicity unaffected.We conclude that clinical thalamic DBS may lead to a neuronal de-rhythmicity and tremor stoppage through masking and/or blocking rhythmic firing of tremor cells.

Action Potentials↗

Deep brain stimulation of the subthalamic nucleus enhances emotional processing in Parkinson disease.

BACKGROUND: High-frequency electrical stimulation of the subthalamic nucleus is a new and highly effective therapy for complications of long-term levodopa therapy and motor symptoms in advanced Parkinson disease (PD). Clinical observations indicate additional influence on emotional behavior. METHODS: Electrical stimulation of deep brain nuclei with pulse rates above 100 Hz provokes a reversible, lesioning-like effect. Here, the effect of deep brain stimulation of the subthalamic nucleus on emotional, cognitive, and motor performance in patients with PD (n = 12) was examined. The results were compared with the effects of a suprathreshold dose of levodopa intended to transiently restore striatal dopamine deficiency. Patients were tested during medication off/stimulation off (STIM OFF), medication off/stimulation on (STIM ON), and during the best motor state after taking levodopa without deep brain stimulation (MED). RESULTS: More positive self-reported mood and an enhanced mood induction effect as well as improvement in emotional memory during STIM ON were observed, while during STIM OFF, patients revealed reduced emotional performance. Comparable effects were revealed by STIM ON and MED. Cognitive performance was not affected by the different conditions and treatments. CONCLUSIONS: Deep brain stimulation of the subthalamic nucleus selectively enhanced affective processing and subjective well-being and seemed to be antidepressive. Levodopa and deep brain stimulation had similar effects on emotion. This finding may provide new clues about the neurobiologic bases of emotion and mood disorders, and it illustrates the important role of the basal ganglia and the dopaminergic system in emotional processing in addition to the well-known motor and cognitive functions.

Basal Ganglia↗

Deep brain stimulation in neuropsychiatric disorders.

Deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus, subthalamic nucleus, and internal globus pallidus has been put forth as an alternative to surgical ablation for the treatment of movement disorders. In this paper, the authors discuss the history and putative physiologic mechanisms underlying DBS of these target regions. The authors then review empirical findings pertaining to the effects of DBS on neurological symptoms, cognitive functioning, and psychiatric symptoms in Parkinson's disease and essential tremor, the disorders for which the procedure has been most extensively applied. Finally, emerging and potential novel areas of application of DBS for the treatment of neuropsychiatric disorders and symptoms are discussed.

Brain↗

Deep brain stimulation for hyperkinetic disorders.

Deep brain stimulation (DBS) has a record of safety and efficacy for an expanding range of indications. Recently,the Food and Drug Administration provided approval through a Humanitarian Device Exemption for DBS of the globus pallidus internus and subthalamic nucleus for the treatment of dystonia. There is increasing clinical experience demonstrating that DBS is also effective for other hyperkinetic disorders such as chorea from a variety of causes. The selection criteria, intraoperative targeting, and the postoperative management of DBS for hyperkinetic disorders are discussed.

Adult↗

Neurophysiologic aspects of deep brain stimulation.

Implanting electrodes for deep brain stimulation (DBS) allows performance of a number of different neurophysiologic studies. Before definitive internalization of the device, recording and stimulation through the electrodes is possible. Stimulation of the globus pallidum produced a mixture of excitation and inhibition of ongoing muscle activity. The excitatory response is probably produced by activation of the large-diameter fibers of the corticospinal tract. Stimulation of the thalamus is mainly associated with EMG inhibition. These findings indicate that the effect of stimulation may vary in different targets and that the mechanism of action of DBS is heterogeneous. A different type of study concerns those undertaken after chronic DBS of the subthalamic nucleus (STN) and globus pallidum internum (GPi) in parkinsonian patients. Cortical mechanisms subserving movement preparation and execution have been assessed. The main findings were that stimulation had a more prominent effect on execution than on preparation and that this was greater in patients treated with STN DBS than GPi DBS.

Electric Stimulation Therapy↗

[Parkinson's disease: deep brain stimulation]

The effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the internal pallidum (GPi) on the parkinsonian triad and on levodopa-induced dyskinesias are very similar. The antiakinetic effect of STN DBS seems to be slightly better. On the contrary to pallidal DBS, stimulation of the STN allows to reduce dopaminergic treatment by more than 50p.100 on average. Moreover, the current drain is smaller in STN. Thus, the STN is a low budget target compared to the GPi. STN DBS seems to be as effective on PD tremor as stimulation of the classic thalamic target, the ventral intermediate nucleus (Vim), whereas Vim stimulation has no effect on akinesia and very little on levodopa-induced dyskinesias. Thus, the STN has become the main target nucleus for DBS in PD, which is most often performed bilaterally in one surgical procedure. There is a good correlation of the preoperative response to levodopa and postoperative effects of bilateral STN DBS and this defines the patient population. Given the large patient population, simple guidelines for patient selection are developed. The referring physician can preselect patients based mainly on age (less than 70), absence of dementia and presence of severe disability related to motor fluctuations or dyskinesias. It is the responsibility of the operating centre to determine the levodopa response, to confirm the diagnosis, to rule out contraindications and to make sure that the medical treatment cannot be further optimised. Severe surgical complications with permanent sequels are relatively rare, about 1p.100 per implanted side. The patient selection, the precision of the surgery and the quality of the postoperative follow-up are the three main determinants of success.

Journal Article↗

Deep brain stimulation for Parkinson's disease.

Deep brain stimulation at high frequency was first used in 1997 to replace thalamotomy in treating the characteristic tremor of Parkinson's disease, and has subsequently been applied to the pallidum and the subthalamic nucleus. The subthalamic nucleus is a key node in the functional control of motor activity in the basal ganglia. Its inhibition suppresses symptoms in animal models of Parkinson's disease, and high frequency chronic stimulation does the same in human patients. Acute and long-term results after deep brain stimulation show a dramatic and stable improvement of a patient's clinical condition, which mimics the effects of levodopa treatment. The mechanism of action may involve a functional disruption of the abnormal neural messages associated with the disease. Long-term changes, neural plasticity and neural protection might be induced in the network. Similar effects of stimulation and lesioning have led to the extension of this technique for other targets and diseases.

Electric Stimulation Therapy↗

Electric field and stimulating influence generated by deep brain stimulation of the subthalamic nucleus.

OBJECTIVE: The goal of this project was to develop a quantitative understanding of the volume of axonal tissue directly activated by deep brain stimulation (DBS) of the subthalamic nucleus (STN). METHODS: The 3-dimensionally inhomogeneous and anisotropic tissue medium surrounding DBS electrodes complicates our understanding of the electric field and tissue response generated by the stimulation. We developed finite element computer models to address the effects of DBS in a homogeneous isotropic medium, and a medium with tissue conductivity properties derived from human diffusion tensor magnetic resonance data. The second difference of the potential distribution generated in the tissue medium was used as a predictor of the volume of tissue supra-threshold for axonal activation. RESULTS: The model predicts that clinically effective stimulation parameters (-3 V; 0.1 ms; 150 Hz) result in activation of large diameter (5.7 microm) myelinated axons over a volume that spreads outside the borders of the STN. The shape of the activation volume was dependent on the strong dorsal-ventral anisotropy of the internal capsule, and the moderate anterior-posterior anisotropy of the region around zona incerta. CONCLUSIONS: Small deviations ( approximately 1 mm) in the electrode position within STN can substantially alter the shape of the activation volume as well as its spread to neighboring structures. SIGNIFICANCE: STN DBS represents an effective treatment for medically refractory movement disorders such as Parkinson's disease. However, stimulation induced side effects such as tetanic muscle contraction, speech disturbance and ocular deviation are not uncommon. Quantitative characterization of the spread of stimulation will aid in the development of techniques to maximize the efficacy of DBS.

Artifacts↗

Deep brain stimulation in movement and psychiatric disorders.

Deep brain stimulation (DBS) is the most focal and invasive of the electromagnetic brain stimulation therapies. A subcutaneous pulse generator provides continuous stimulation of circumscribed brain tissue via a multicontact microelectrode that terminates within its target. The result is an adjustable, reversible, and specific therapy. Despite limited understanding of its mechanisms of action, DBS efficacy has been established in several movement disorders, and promising reports have emerged for Tourette syndrome, obsessive-compulsive disorder, and major depression. Deep brain stimulation may prove to be a reasonable option for severely ill and treatment-resistant patients who otherwise have limited therapeutic options and a poor prognosis.

Animals↗

Lower urinary tract symptoms and bladder control in advanced Parkinson's disease: effects of deep brain stimulation in the subthalamic nucleus.

Deep brain stimulation in the subthalamic nucleus (STN) leads to significant improvement in motor function in patients with advanced Parkinson's disease (PD). In this prospective study including 16 patients with PD, we investigated (1) lower urinary tract symptoms (LUTS) by questionnaires International Prostate Symptom Score (IPSS, symptoms only) and Danish Prostate Symptom Score (DanPSS, symptoms and bother of symptoms) and (2) bladder control (assessed by urodynamics) before and after implantation of electrodes in the STN. PD symptoms (Unified Parkinson's Disease Rating Scale score) improved significantly (P < 0.0001), and symptoms of overactive bladder (IPSS) decreased along with the troublesome symptoms of overactive bladder (DanPSS; P < 0.01 for both). Urodynamic parameters before and after implantation of electrodes in the STN, evaluated with and without the stimulation on, did not change significantly.

Adult↗