Comparative neural correlates of DBS and MRgFUS lesioning for tremor control in essential tremor.

BACKGROUND: Given high rates of early complications and non-reversibility, refined targeting is necessitated for magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for essential tremor (ET). Selection of lesion location can be informed by considering optimal stimulation area from deep brain stimulation (DBS). METHODS: 118 patients with ET who received DBS (39) or MRgFUS (79) of the ventral intermediate nucleus (VIM) underwent stimulation/lesion mapping, probabilistic mapping of clinical efficacy and normative structural connectivity analysis. The efficacy maps were compared, which depict the relationship between stimulation/lesion location and clinical outcome. RESULTS: Efficacy maps overlap around the VIM ventral border and encompass the dentato-rubro-thalamic tract. While the MRgFUS map extends inferiorly into the posterior subthalamic area, the DBS map spreads inside the VIM antero-superiorly. CONCLUSION: Comparing the efficacy maps of DBS and MRgFUS suggests a potential alternative location for lesioning, more antero-superiorly. This may reduce complications, without sacrificing efficacy, and individualise targeting. TRIAL REGISTRATION NUMBER: NCT02252380.

Neurophysiological responses of globus pallidus internus during the auditory oddball task in Parkinson's disease.

Parkinson's disease can be associated with significant cognitive impairment that may lead to dementia. Deep brain stimulation (DBS) of the subthalamic nucleus is an effective therapy for motor symptoms but is associated with cognitive decline. DBS of globus pallidus internus (GPi) poses less risk of cognitive decline so may be the preferred target. A research priority is to identify biomarkers of cognitive decline in this population, but efforts are hampered by a lack of understanding of the role of the different basal ganglia nuclei, such as the globus pallidus, in cognitive processing. During deep brain stimulation (DBS) surgery, we monitored single units, beta oscillatory LFP activity as well as event related potentials (ERPs) from the globus pallidus internus (GPi) of 16 Parkinson's disease patients, while they performed an auditory attention task. We used an auditory oddball task, during which one standard tone is presented at regular intervals and a second deviant tone is presented with a low probability that the subject is requested to count and report at the end of the task. All forms of neuronal activity studied were selective modulated by the attended tones. Of 62 neurons studied, the majority (51 or 82%) responded selectively to the deviant tone. Beta oscillatory activity showed an overall desynchronization during both types of attended tones interspersed by bursts of beta activity giving rise to peaks at a latency of around 200 ms after tone onset. cognitive ERPs recorded in GPi were selective to the attended tone and the right-side cERP was larger than the left side. The averages of trials showing a difference in beta oscillatory activity between deviant and standard also had a significant difference in cERP amplitude. In one block of trials, the random occurrence of 3 deviant tones in short succession silenced the activity of the GPi neuron being recorded. Trial blocks where a clear difference in LFP beta was seen were twice as likely to yield a correct tone count (25 vs 11). The data demonstrate strong modulation of GPi neuronal activity during the auditory oddball task. Overall, this study demonstrates an involvement of GPi in processing of non-motor cognitive tasks such as working memory and attention, and suggests that direct effects of DBS in non-motor GPi may contribute to cognitive changes observed post-operatively.

Bilateral Focused Ultrasound Thalamotomy for Essential Tremor (BEST-FUS Phase 2 Trial).

BACKGROUND: In patients with medically refractory essential tremor, unilateral magnetic resonance-guided focused ultrasound thalamotomy can improve contralateral tremor. However, this procedure does not address ipsilateral symptoms. OBJECTIVE: The objective of the current study was to determine whether bilateral thalamotomies can be performed with an acceptable safety profile where benefits outweigh adverse effects. METHODS: We conducted a prospective, single-arm, single-blinded phase 2 trial of second-side magnetic resonance-guided focused ultrasound thalamotomy in patients with essential tremor. Patients were followed for 3 months. The primary outcome was the change in quality of life relative to baseline, as well as the answer to the question "Given what you know now, would you treat the second side again?". Secondary outcomes included tremor, gait, speech, and adverse effects. RESULTS: Ten patients were analyzed. The study met both primary outcomes, with the intervention resulting in clinically significant improvement in quality of life at 3 months (mean Quality of Life in Essential Tremor score difference, 19.7; 95%CI, 8.0-31.4; P = 0.004) and all patients reporting that they would elect to receive the second-side treatment again. Tremor significantly improved in all patients. Seven experienced mild adverse effects, including 2 with transient gait impairment and a fall, 1 with dysarthria and dysphagia, and 1 with mild dysphagia persisting at 3 months. CONCLUSIONS: Staged bilateral magnetic resonance-guided focused ultrasound thalamotomy can be performed with a reasonable safety profile similar to that seen with unilateral thalamotomy and improves the tremor and quality of life of patients with essential tremor. Longer-term follow-up and continued accrual in the phase 3 trial will be required to validate these findings. © 2021 International Parkinson and Movement Disorder Society.

Adoption of focused ultrasound thalamotomy for essential tremor: why so much fuss about FUS?

BACKGROUND: Focused ultrasound (FUS) was approved as a new treatment modality for essential tremor (ET) in 2016. The goal of this study was to quantify FUS adoption for ET and understand its drivers. METHODS: The adoption of the various surgical options for ET was estimated using three measures: the number of presentations on the various surgical treatments for ET at specialised international meetings, the number of original papers published as identified by literature searches and the number of thalamotomy procedures performed worldwide for ET as provided by device manufacturers' registries. RESULTS: First, we found that the number of presentations related to lesioning procedures is increasing relative to deep brain stimulation (DBS) at international meetings. Second, there are already more publications on FUS (93) than stereotactic radiosurgery (SRS) (68) or radiofrequency (43) for ET, although they still lag behind DBS papers (750). Third, the number of annual FUS thalamotomies performed for ET (n>1200 in 2019) in 44 centres has surpassed the annual procedures across 342 Gamma Knife units (n<400, 2018) but is yet to reach the number of DBS cases for ET estimated at over 2400/year. CONCLUSION: FUS is being rapidly adopted for the treatment of ET. We hypothesise that its perceived minimally invasive nature coupled with the ability to perform intraoperative clinical assessments, its immediate effects and active marketing efforts are contributing factors. As lesioning modalities for the treatment of ET are reappraised, the superior popularity of FUS over SRS appears to arise for reasons other than differences in clinical outcomes.

Multimodal MRI for MRgFUS in essential tremor: post-treatment radiological markers of clinical outcome.

BACKGROUND: MRI-guided focused ultrasound (MRgFUS) thalamotomy is a promising non-invasive treatment option for medication-resistant essential tremor. However, it has been associated with variable efficacy and a relatively high incidence of adverse effects. OBJECTIVES: To assess the evolution of radiological findings after MRgFUS thalamotomy and to evaluate their significance for clinical outcomes. METHODS: Ninety-four patients who underwent MRgFUS between 2012 and 2017 were retrospectively evaluated. Lesion characteristics were assessed on routine MRI sequences, as well as with tractography. Relationships between imaging appearance, extent of white matter tract lesioning (59/94, on a 4-point scale) and clinical outcome were investigated. Recurrence was defined as >33% loss of tremor suppression at 3 months relative to day 7. RESULTS: Acute lesions demonstrated blood products, surrounding oedema and peripheral diffusion restriction. The extent of dentatorubrothalamic tract (DRTT) lesioning was significantly associated with clinical improvement at 1 year (t=4.32, p=0.001). Lesion size decreased over time (180.8±91.5 mm3 at day 1 vs 19.5±19.3 mm3 at 1-year post-treatment). Higher post-treatment oedema (t=3.59, p<0.001) was associated with larger lesions at 3 months. Patients with larger lesions at day 1 demonstrated reduced rates of tremor recurrence (t=2.67, p=0.019); however, lesions over 170 mm3 trended towards greater incidence of adverse effects (sensitivity=0.60, specificity=0.63). Lesion encroachment on the medial lemniscus (Sn=1.00, Sp=0.32) and pyramidal tract (Sn=1.00, Sp=0.12) were also associated with increased adverse effects incidence. CONCLUSION: Lesion size at day 1 predicts symptom recurrence, with fewer recurrences seen with larger lesions. Greater DRTT lesioning is associated with treatment efficacy. These findings may have implications for lesion targeting and extent. TRIAL REGISTRATION NUMBER: NCT02252380.

The Utility of Diffusion Tensor Imaging in Neuromodulation: Moving Beyond Conventional Magnetic Resonance Imaging.

OBJECTIVES: Conventional targeting methods for neuromodulation therapies are insufficient for visualizing targets along white matter pathways and localizing targets in patient-specific space. Diffusion tensor imaging (DTI) holds promise for enhancing neuromodulation targeting by allowing detailed visualization of white matter tracts and their connections on an individual level. MATERIAL AND METHODS: We review the literature on DTI and neuromodulation, focusing on clinical studies that have utilized DTI tractography for surgical neuromodulation planning. This primarily includes the growing number of studies on tractography-guided targeting in deep brain stimulation as well as magnetic resonance-guided focused ultrasound. RESULTS: In this review, we discuss three main topics: 1) an overview of the basic principles of DTI, its metrics, and tractography, 2) the evolution and utility of DTI to better guide neuromodulation targets, and 3) the ability of DTI to investigate structural connectivity and brain networks, and how such a network perspective may be an integral part of identifying new or optimal neuromodulation targets. CONCLUSION: There is increasing evidence that DTI is superior to conventional targeting methods with respect to improving brain stimulation therapies. DTI has the ability to better define anatomical targets by allowing detailed visualization of white matter tracts and localizing targets based on individual anatomy. Network analyses can lead to the identification of new or optimal stimulation targets based on understanding how target regions are connected. The integration of DTI as part of routine MRI and surgical planning offers a more personalized approach to therapy and may be an important path for the future of neuromodulation.

Dystonia as complication of thalamic neurosurgery.

BACKGROUND: Thalamotomy and deep brain stimulation of the ventralis intermedius nucleus are effective symptomatic treatments for tremor, irrespective of the underlying diagnosis. METHODS AND RESULTS: Herein we describe six tremor patients (2 Parkinson's disease, 1 dystonic tremor, 2 Essential tremor plus dystonia, 1 Essential tremor plus ataxia) who underwent thalamic neurosurgery and acutely or sub-acutely developed dystonia that was permanent in three cases and could not be managed with any adjustments in the stimulation settings. Tremor response was excellent. We argue that thalamic procedures disrupted either or both the cerebello-thalamic and the cortico-striato-pallido-thalamo-cortical loop resulting in an increase of the thalamo-cortical outflow and subsequent change in the clinical picture from tremor to dystonia. CONCLUSION: Thalamic neurosurgery might be rarely complicated by dystonia. Why some patients are more prone to develop this adverse event is still unknown and possibly related to intrinsic factors, which certainly need further studies.

Outcomes from stereotactic surgery for essential tremor.

There are several different surgical procedures that are used to treat essential tremor (ET), including deep brain stimulation (DBS) and thalamotomy procedures with radiofrequency (RF), radiosurgery (RS) and most recently, focused ultrasound (FUS). Choosing a surgical treatment requires a careful presentation and discussion of the benefits and drawbacks of each. We conducted a literature review to compare the attributes and make an appraisal of these various procedures. DBS was the most commonly reported treatment for ET. One-year tremor reductions ranged from 53% to 63% with unilateral Vim DBS. Similar improvements were demonstrated with RF (range, 74%-90%), RS (range, 48%-63%) and FUS thalamotomy (range, 35%-75%). Overall, bilateral Vim DBS demonstrated more improvement in tremor reduction since both upper extremities were treated (range, 66%-78%). Several studies show continued beneficial effects from DBS up to five years. Long-term follow-up data also support RF and gamma knife radiosurgical thalamotomy treatments. Quality of life measures were similarly improved among patients who received all treatments. Paraesthesias, dysarthria and ataxia were commonly reported adverse effects in all treatment modalities and were more common with bilateral DBS surgery. Many of the neurological complications were transient and resolved after surgery. DBS surgery had the added benefit of programming adjustments to minimise stimulation-related complications. Permanent neurological complications were most commonly reported for RF thalamotomy. Thalamic DBS is an effective, safe treatment with a long history. For patients who are medically unfit or reluctant to undergo DBS, several thalamic lesioning methods have parallel benefits to unilateral DBS surgery. Each of these surgical modalities has its own nuance for treatment and patient selection. These factors should be carefully considered by both neurosurgeons and patients when selecting an appropriate treatment for ET.

Focused ultrasound thalamotomy location determines clinical benefits in patients with essential tremor.

Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy is a novel and minimally invasive ablative treatment for essential tremor. The size and location of therapeutic lesions producing the optimal clinical benefits while minimizing adverse effects are not known. We examined these relationships in patients with essential tremor undergoing MRgFUS. We studied 66 patients with essential tremor who underwent MRgFUS between 2012 and 2017. We assessed the Clinical Rating Scale for Tremor (CRST) scores at 3 months after the procedure and tracked the adverse effects (sensory, motor, speech, gait, and dysmetria) 1 day (acute) and 3 months after the procedure. Clinical data associated with the postoperative Day 1 lesions were used to correlate the size and location of lesions with tremor benefit and acute adverse effects. Diffusion-weighted imaging was used to assess whether acute adverse effects were related to lesions encroaching on nearby major white matter tracts (medial lemniscus, pyramidal, and dentato-rubro-thalamic). The area of optimal tremor response at 3 months after the procedure was identified at the posterior portion of the ventral intermediate nucleus. Lesions extending beyond the posterior region of the ventral intermediate nucleus and lateral to the lateral thalamic border were associated with increased risk of acute adverse sensory and motor effects, respectively. Acute adverse effects on gait and dysmetria occurred with lesions inferolateral to the thalamus. Lesions inferolateral to the thalamus or medial to the ventral intermediate nucleus were also associated with acute adverse speech effects. Diffusion-weighted imaging revealed that lesions associated with adverse sensory and gait/dysmetria effects compromised the medial lemniscus and dentato-rubro-thalamic tracts, respectively. Lesions associated with adverse motor and speech effects encroached on the pyramidal tract. Lesions larger than 170 mm3 were associated with an increased risk of acute adverse effects. Tremor improvement and acute adverse effects of MRgFUS for essential tremor are highly dependent on the location and size of lesions. These novel findings could refine current MRgFUS treatment planning and targeting, thereby improving clinical outcomes in patients.

Physiological mechanisms of thalamic ventral intermediate nucleus stimulation for tremor suppression.

Ventral intermediate thalamic deep brain stimulation is a standard therapy for the treatment of medically refractory essential tremor and tremor-dominant Parkinson's disease. Despite the therapeutic benefits, the mechanisms of action are varied and complex, and the pathophysiology and genesis of tremor remain unsubstantiated. This intraoperative study investigated the effects of high frequency microstimulation on both neuronal firing and tremor suppression simultaneously. In each of nine essential tremor and two Parkinson's disease patients who underwent stereotactic neurosurgery, two closely spaced (600 µm) microelectrodes were advanced into the ventral intermediate nucleus. One microelectrode recorded action potential firing while the adjacent electrode delivered stimulation trains at 100 Hz and 200 Hz (2-5 s, 100 µA, 150 µs). A triaxial accelerometer was used to measure postural tremor of the contralateral hand. At 200 Hz, stimulation led to 68 ± 8% (P < 0.001) inhibition of neuronal firing and a 53 ± 5% (P < 0.001) reduction in tremor, while 100 Hz reduced firing by 26 ± 12% (not significant) with a 17 ± 6% (P < 0.05) tremor reduction. The degree of cell inhibition and tremor suppression were significantly correlated (P < 0.001). We also found that the most ventroposterior stimulation sites, closest to the border of the ventral caudal nucleus, had the best effect on tremor. Finally, prior to the inhibition of neuronal firing, microstimulation caused a transient driving of neuronal activity at stimulus onset (61% of sites), which gave rise to a tremor phase reset (73% of these sites). This was likely due to activation of the excitatory glutamatergic cortical and cerebellar afferents to the ventral intermediate nucleus. Temporal characteristics of the driving responses (duration, number of spikes, and onset latency) significantly differed between 100 Hz and 200 Hz stimulation trains. The subsequent inhibition of neuronal activity was likely due to synaptic fatigue. Thalamic neuronal inhibition seems necessary for tremor reduction and may function in effect as a thalamic filter to uncouple thalamo-cortical from cortico-spinal reflex loops. Additionally, our findings shed light on the gating properties of the ventral intermediate nucleus within the cerebello-thalamo-cortical tremor network, provide insight for the optimization of deep brain stimulation technologies, and may inform controlled clinical studies for assessing optimal target locations for the treatment of tremor.

Gamma oscillations in the somatosensory thalamus of a patient with a phantom limb: case report.

The amputation of an extremity is commonly followed by phantom sensations that are perceived to originate from the missing limb. The mechanism underlying the generation of these sensations is still not clear although the development of abnormal oscillatory bursting in thalamic neurons may be involved. The theory of thalamocortical dysrhythmia implicates gamma oscillations in phantom pathophysiology although this rhythm has not been previously observed in the phantom limb thalamus. In this study, the authors report the novel observation of widespread 38-Hz gamma oscillatory activity in spike and local field potential recordings obtained from the ventral caudal somatosensory nucleus of the thalamus (Vc) of a phantom limb patient undergoing deep brain stimulation (DBS) surgery. Interestingly, microstimulation near tonically firing cells in the Vc resulted in high-frequency, gamma oscillatory discharges coincident with phantom sensations reported by the patient. Recordings from the somatosensory thalamus of comparator groups (essential tremor and pain) did not reveal the presence of gamma oscillatory activity.

Beta oscillatory neurons in the motor thalamus of movement disorder and pain patients.

Excessive beta oscillations (15-25Hz) in the basal ganglia have been linked to the akineto-rigid symptoms of Parkinson's disease (PD) although it remains unclear whether the underlying mechanism is causative or associative. While a number of studies have reported beta activity in the subthalamic nucleus and globus pallidus internus, relatively little is known about the beta rhythm of the motor thalamus and its relation to movement disorders. To test whether thalamic beta oscillations are related to parkinsonian symptoms, we examined the spectral properties of neuronal activity in the ventral thalamic nuclei of five Parkinson's disease patients (two female, age range 50-72years) and compared them to five essential tremor (three female, aged 41-75) and four central pain patients (one female, aged 38-60). Spike and local field potential recordings were obtained during microelectrode-guided localization of thalamic nuclei prior to the implantation of deep brain stimulating electrodes. A total of 118 movement-related neurons in the region of the ventral intermediate nucleus (Vim) were analyzed across all patient groups. Eighty of these neurons (68%) displayed significant oscillatory firing in the beta range with the limbs at rest. In contrast, only 5.7% of the ventral oral posterior (Vop) (χ(2) test, p<0.05) and only 7.2% of the ventral caudal (Vc) neurons fired rhythmically at beta frequency (χ(2) test, p<0.05). Beta power was significantly decreased during limb movements (ANOVA, p<0.05) and was inversely related to tremor-frequency power during tremor epochs in ET and PD (r(2)=0.44). Comparison between patient groups showed that Vim beta power was significantly higher in ET patients versus pain and PD groups (ANOVA, p<0.05). The findings suggest that beta oscillations are found predominantly in Vim and are involved in movement but are not enhanced in tremor-dominant Parkinson's patients.

Acute complications of movement disorders surgery: effects of age and comorbidities.

The most common indication for movement disorder surgery is Parkinson's disease (PD), and the incidence of PD increases with age. The analysis reported here was undertaken with the primary goal of examining whether there is a relationship between peri-operative complications and age. The Nationwide Inpatient Sample (Agency for Healthcare Research and Quality, Rockville, MD, USA) was queried for 10 years beginning in 1999 for patients undergoing deep brain stimulator insertion, pallidotomy, and thalamotomy for treatment of PD, essential tremor, and dystonia. Inpatient complications, including death, stroke (both ischemic and hemorrhagic), and other overall complications were examined. The relative risks associated with advanced age; primary diagnosis; treatment modality; the diagnoses of hypertension, diabetes, and nicotinism; and the cumulative number of comorbidities were examined. There were 5464 patients who met inclusion criteria, including 4145 patients treated for PD and 4961 patients treated with deep brain stimulation (DBS). Overall in-hospital mortality was 0.26%, with 0.15% related to surgical factors. There was a correlation between in-hospital mortality, increasing age, and number of medical comorbidities. After multivariate regression no factor remained predictive of mortality. Having more than 1 medical comorbidity or PD increased the risk of in-hospital complications. Patients with PD were more likely to suffer hemorrhage or stroke. Hypertension, diabetes, nicotinism, and modality of treatment were not associated with increased mortality, hemorrhage or stroke risk, or in-hospital mortality in univariate or multivariate analysis. Both age and medical comorbidity are correlated with in-hospital complications, but age appears to serve as a surrogate for comorbidity. Surgery for PD appears to carry an increased risk of hemorrhage or stroke and in-hospital complications.

Spinal cord stimulators and radiotherapy: first case report and practice guidelines.

Spinal cord stimulators (SCS) are a well-recognised treatment modality in the management of a number of chronic neuropathic pain conditions, particularly failed back syndrome and radiculopathies. The implantable pulse generator (IPG) component of the SCS is designed and operates in a similar fashion to that of a cardiac pacemaker. The IPG consists of an electrical generator, lithium battery, transmitter/receiver and a minicomputer. When stimulated, it generates pulsed electrical signals which stimulate the dorsal columns of the spinal cord, thus alleviating pain. Analogous to a cardiac pacemaker, it can be potentially damaged by ionising radiation from a linear accelerator, in patients undergoing radiotherapy. Herein we report our clinical management of the first reported case of a patient requiring adjuvant breast radiotherapy who had a SCS in situ. We also provide useful practical recommendations on the management of this scenario within a radiation oncology department.

Gamma knife thalamotomy for disabling tremor: a blinded evaluation.

BACKGROUND: Gamma knife thalamotomy (GKT) has been used as a therapeutic option for patients with disabling tremor refractory to medications. Impressive improvement of tremor has been reported in the neurosurgical literature, but the reliability of such data has been questioned. OBJECTIVE: To prospectively evaluate clinical outcomes after GKT for disabling tremor with blinded assessments. DESIGN: Prospective study with blinded independent neurologic evaluations. SETTING: University hospital. PATIENTS: Consecutive patients who underwent unilateral GKT for essential tremor and Parkinson disease tremor at our center. These patients were unwilling or deemed unsuitable candidates for deep brain stimulation or other surgical procedures. INTERVENTIONS: Unilateral GKT and regular follow-up evaluations for up to 30 months, with blinded video evaluations by a movement disorders neurologist. MAIN OUTCOME MEASURES: Clinical outcomes, as measured by the Fahn-Tolosa-Marin Tremor Rating Scale and activities of daily living scores, and incidence of adverse events. RESULTS: From September 1, 2006, to November 30, 2008, 18 patients underwent unilateral GKT for essential tremor and Parkinson disease tremor at our center. Videos for 14 patients (11 with essential tremor, 3 with Parkinson disease tremor) with at least 6 months' postoperative follow-up were available for analysis (mean [SD] follow-up duration, 19.2 [7.3] months; range, 7-30 months). The Fahn-Tolosa-Marin Tremor Rating Scale activities of daily living scores improved significantly after GKT (P = .03; median and mean change scores, 2.5 and 2.7 points, respectively [range of scale was 0-27]), but there was no significant improvement in other Fahn-Tolosa-Marin Tremor Rating Scale items (P = .53 for resting tremor, P = .24 for postural tremor, P = .62 for action tremor, P = .40 for drawing, P > .99 for pouring water, P = .89 for head tremor). Handwriting and Unified Parkinson's Disease Rating Scale activities of daily living scores tended to improve (P = .07 and .11, respectively). Three patients developed delayed neurologic adverse events. CONCLUSIONS: Overall, we found that GKT provided only modest antitremor efficacy. Of the 2 patients with essential tremor who experienced marked improvement in tremor, 1 subsequently experienced a serious adverse event. Further prospective studies with careful neurologic evaluation of outcomes are necessary before GKT can be recommended for disabling tremor on a routine clinical basis.

Dopamine-dependent high-frequency oscillatory activity in thalamus and subthalamic nucleus of patients with Parkinson's disease.

In recent years there has been great interest in oscillatory activity in the brain and in the role of pathological oscillations in the basal ganglia in mediating some of the symptoms of Parkinson's disease (PD). In this study, thalamic and subthalamic nucleus local field potentials were intraoperatively recorded from pairs of closely separated microelectrodes in six PD patients ON and OFF dopaminergic medication. Using correlation and coherence analyses, we found high-frequency oscillatory activity in the 110-170 Hz band in thalamus in patients OFF dopamine. These oscillations were significantly reduced after administration of dopamine-replacement therapy. In contrast, activity in the lower frequencies (the theta and beta ranges) was increased. However, in subthalamic nucleus, we observed an increase in high-frequency oscillatory activity (150-200 Hz), and a reduction of the activity in the low-frequency range after levodopa administration. These findings confirm and extend earlier findings suggesting that in PD there are marked changes in basal ganglia oscillatory activity and that these can be reversed after dopaminergic therapy.

Deep brain stimulation for the treatment of epilepsy.

During the last decade, deep brain stimulation (DBS) has been used to treat several neurologic disorders, including epilepsy. Promising results have been reported with stimulation in different brain regions. At present however, several issues remain unanswered. As an example, it is still unclear whether particular seizure types and syndromes should be treated with DBS in different targets or with different stimulation parameters. In addition, clinical, electrophysiological and anatomical features capable of predicting a good postoperative outcome are still unknown. We review the published literature on DBS, cortical and cerebellar stimulation for the treatment of epilepsy focusing predominantly on the rationale and clinical outcome in each target.

Enhanced synchronization of thalamic theta band local field potentials in patients with essential tremor.

Local field potentials (LFPs) were recorded in 13 patients from pairs of microelectrodes driven through thalamus during functional localization prior to implantation of a thalamic deep brain stimulation electrode for treatment of tremor or pain. Six patients had a history of essential tremor (ET), 3 of multiple sclerosis, and the remaining 4 had symptoms of chronic pain. Specific to the ET group was the observation that oscillatory field potentials recorded from the two microelectrodes in the motor thalamus (ventralis intermedius--Vim, ventralis oralis posterior--Vop) were highly coherent at frequencies characteristic of pathological tremor (4-7 Hz). This stands in contrast to the significantly more desynchronized state observed in the somatosensory thalamus (ventralis caudalis--Vc) for that frequency band. In addition, higher frequency coherent oscillations typically associated with physiological tremor (8-12 Hz) were observed in the ET patients in motor thalamus and Vc and in motor thalamus of pain patients. An examination of the inter-frequency correlation of the LFPs in Vim and Vop showed that the low frequency theta waves correlated with high frequency oscillations in the beta and gamma ranges. These findings are consistent with and extend those of other studies suggesting that alterations in thalamic oscillatory activity are involved in the pathophysiology of ET and furthermore suggest that increased synchronization in the 4-7 Hz range is related to the occurrence of tremor in the ET patient group. Furthermore, they support the idea that therapies such as lesions and high frequency stimulation of the motor thalamus are effective in reducing tremor symptoms since they destroy the abnormal low frequency synchronization in motor thalamus.

Chronic anterior thalamus stimulation for intractable epilepsy.

PURPOSE: A significant number of patients with epilepsy remain poorly controlled despite antiepileptic medication (AED) treatment and are not eligible for resective surgery. Novel therapeutic methods are required to decrease seizure burden in this population. Several observations have indicated that the anterior thalamic region plays an important role in the maintenance and propagation of seizures. We investigated neuromodulation of the anterior thalamus by using deep-brain stimulation (DBS) in patients with intractable seizures. METHODS: Five patients with medically refractory epilepsy underwent stereotactic placement of and received stimulation through bilateral DBS electrodes in the anterior thalamus. RESULTS: Treatment showed a statistically significant decrease in seizure frequency, with a mean reduction of 54% (mean follow-up, 15 months). Two of the patients had a seizure reduction of > or =75%. No adverse effects were observed after DBS electrode insertion or stimulation. Unexpectedly, the observed benefits did not differ between stimulation-on and stimulation-off periods. CONCLUSIONS: DBS of the anterior thalamus is a safe procedure and possibly effective in patients with medically resistant seizures.