Neural signal data collection and analysis of Percept™ PC BrainSense recordings for thalamic stimulation in epilepsy.

Deep brain stimulation (DBS) using Medtronic's Percept™ PC implantable pulse generator is FDA-approved for treating Parkinson's disease (PD), essential tremor, dystonia, obsessive compulsive disorder, and epilepsy. Percept™ PC enables simultaneous recording of neural signals from the same lead used for stimulation. Many Percept™ PC sensing features were built with PD patients in mind, but these features are potentially useful to refine therapies for many different disease processes. When starting our ongoing epilepsy research study, we found it difficult to find detailed descriptions about these features and have compiled information from multiple sources to understand it as a tool, particularly for use in patients other than those with PD. Here we provide a tutorial for scientists and physicians interested in using Percept™ PC's features and provide examples of how neural time series data is often represented and saved. We address characteristics of the recorded signals and discuss Percept™ PC hardware and software capabilities in data pre-processing, signal filtering, and DBS lead performance. We explain the power spectrum of the data and how it is shaped by the filter response of Percept™ PC as well as the aliasing of the stimulation due to digitally sampling the data. We present Percept™ PC's ability to extract biomarkers that may be used to optimize stimulation therapy. We show how differences in lead type affects noise characteristics of the implanted leads from seven epilepsy patients enrolled in our clinical trial. Percept™ PC has sufficient signal-to-noise ratio, sampling capabilities, and stimulus artifact rejection for neural activity recording. Limitations in sampling rate, potential artifacts during stimulation, and shortening of battery life when monitoring neural activity at home were observed. Despite these limitations, Percept™ PC demonstrates potential as a useful tool for recording neural activity in order to optimize stimulation therapies to personalize treatment.

Decreasing the Symptoms of Essential Tremor With Medical Painting Therapy.

Introduction Essential tremor (ET) is a common movement disorder in the elderly. Bilateral postural tremor usually involves the hands and forearms; the primary diagnostic criteria can be with or without a kinetic tremor. Anticonvulsants are frequently prescribed as a primary medication, and botulinum toxin and deep brain stimulation as secondary options. In this case report, a patient with ET received medical painting therapy guided by the principles of anthroposophy and the work of Liane Collot d´Herbois. Case Presentation A 78-year-old woman presented ET, depression and bipolar symptoms. Additionally, she reported insomnia, constipation, lumbar pain, and sciatic pain. Current medications included lithium carbonate, folic acid, levothyroxine, and zinc, and she had refused to take propranolol for her ET. She agreed to begin medical painting therapy. Over 5 months, she had 16 sessions of medical painting therapy, carried out in 2 stages. The first stage consisted of 6 free painting sessions for patient evaluation, followed by the second stage of 10 therapeutic sessions. Conclusion The patient reported an increased quality of life (including emotional aspects) and a decrease in her ET, as evidenced by the patient's handwriting. Further research is needed to understand the strengths and limitations of this therapy for ET and related conditions.

Rationale and Evidence for Peripheral Nerve Stimulation for Treating Essential Tremor.

Background: There is growing recognition of peripheral stimulation techniques for controlling arm symptoms in essential tremor (ET). Recently, the FDA gave clearance to the Cala system, a device worn around the wrist to treat arm tremors. The Cala system stimulates the sensory afferents of the peripheral nerves with high-frequency pulses. These pulses are delivered to the median and radial nerves alternately at the tremor frequency of the individual patient. Methods: The PubMed database was searched using the terms ("Essential Tremor"[Mesh] OR "essential tremor" [Title/Abstract] OR "tremor" [Title/Abstract]) AND ("peripheral arm stimulation" [Title/Abstract] OR "Cala device" [Title/Abstract] OR "sensory afferent stimulation" [Title/Abstract] OR "afferent stimulation" [Title/Abstract] OR "arm stimulation" [Title/Abstract] OR "peripheral nerve stimulation" [Title/Abstract]). Results: The search yielded 54 articles. Many studies discussed the rationale and various strategies for peripheral modulation of tremor. While the Cala system was found to be safe and well-tolerated in ET, data on efficacy revealed mixed findings. In a large randomized, blinded trial (n = 77), the primary outcome evaluated with spiral drawing task did not improve but the secondary outcomes reflected by the arm tremor severity and the activities of the daily living score revealed 20-25% improvements. A subsequent trial (n = 323) found that the in-home use of the Cala device led to improvements of similar magnitude lasting for at least three months but the clinical assessments were open-labeled. Discussion: Peripheral stimulation techniques are promising therapeutic modalities for treating ET symptoms. Stimulation of sensory afferent nerve fibers at the wrist can potentially modulate the peripheral and central components of the tremor network. Although the Cala system is user-friendly, safe, and well-tolerated, the current clinical evidence on the efficacy is inconsistent and insufficient. Thus, more data is warranted for implementing peripheral nerve stimulation as a standard of care for ET. Highlights: The current review discusses the rationale, background, and potential mechanisms for using peripheral arm stimulation devices for treating ET. The Cala system is a wrist-worn peripheral nerve stimulation device that received FDA clearance to treat arm tremors. The current review evaluates the evidence for the safety and efficacy of using the Cala system and similar devices in clinical practice.

Reduction of neuronal hyperexcitability with modulation of T-type calcium channel or SK channel in essential tremor.

Essential tremor is one of the most prevalent movement disorders. Propranolol and primidone are the first-line pharmacological therapies. They provide symptomatic control in less than 50% of patients. Topiramate, alprazolam, clonazepam, gabapentin, and botulinum toxin injections are the next line of treatments. These medications lead to modest improvements and are therefore commonly used as add-on agents. Surgical therapies, including deep brain stimulation (DBS) surgery and focused ultrasound beam targeted to the thalamus, are considered for treating tremor refractory to medications and lead to greater than 75% improvements in tremor symptoms. However, DBS is a costly and an invasive procedure; some patients report tolerance to benefits. Focused ultrasound therapy leading to brain lesions is associated with a possibility for permanent clinical deficits. Therefore, research efforts to develop the next generation of oral medications with greater benefits and lesser adverse effects are warranted. There is considerable evidence that the increased functions of calcium channels (P/Q-type and T-type channels) and reduced functions of calcium-activated potassium channels (SK channels) located in the neuronal membranes lead to tremor oscillations. Consequently, many new pharmacological studies have targeted these channels to leverage better clinical outcomes. The current review will discuss the pathophysiology, the specific importance of these channels, and the early clinical experience of using compounds targeting these channels to treat essential tremor.

Deep brain stimulation and other surgical modalities for the management of essential tremor.

INTRODUCTION: Surgical treatments are considered for essential tremor (ET) when patients do not respond to oral pharmacological therapies. These treatments mainly comprise radiofrequency (RF) thalamotomy, gamma knife radiosurgery (GKRS), deep brain stimulation (DBS), and focused ultrasound (FUS) procedures. AREAS COVERED: We reviewed the strengths and weaknesses of each procedure and clinical outcomes for 7 RF studies (n = 85), 11 GKRS (n = 477), 33 DBS (n = 1061), and 13 FUS studies (n = 368). A formal comparison was not possible given the heterogeneity in studies. Improvements were about 42%-90% RF, 10%-79% GKRS, 45%-83% DBS, 42%-83% FUS at short-term follow-up (<12 months) and were about 54%-82% RF, 11%-84% GKRS, 18%-92% DBS, and 42%-80% FUS at long-term follow-up (>12 months). EXPERT OPINION: We found DBS with inherent advantages of being an adjustable and reversible procedure as the most frequently employed surgical procedure for control of ET symptoms. FUS is a promising procedure but has limited applicability for unilateral control of symptoms. RF is invasive, and GKRS has unpredictable delayed effects. Each of these surgical modalities has advantages and limitations that need consideration when selecting a treatment for the ET patients.

Fully implanted adaptive deep brain stimulation in freely moving essential tremor patients.

OBJECTIVE: Deep brain stimulation (DBS) is a safe and established treatment for essential tremor (ET) and several other movement disorders. One approach to improving DBS therapy is adaptive DBS (aDBS), in which stimulation parameters are modulated in real time based on biofeedback from either external or implanted sensors. Previously tested systems have fallen short of translational applicability due to the requirement for patients to continuously wear the necessary sensors or processing devices, as well as privacy and security concerns. APPROACH: We designed and implemented a translation-ready training data collection system for fully implanted aDBS. Two patients chronically implanted with electrocorticography strips over the hand portion of M1 and DBS probes in the ipsilateral ventral intermediate nucleus of the thalamus for treatment of ET were recruited for this study. Training was conducted using a translation-ready distributed training procedure, allowing a substantially higher degree of control over data collection than previous works. A linear classifier was trained using this system, biased towards activating stimulation in accordance with clinical considerations. MAIN RESULTS: The clinically relevant average false negative rate, defined as fraction of time during which stimulation dropped below [Formula: see text] clinical levels during movement epochs, was 0.036. Tremor suppression, calculated through analysis of gyroscope data, was 33.2% more effective on average with aDBS than with continuous DBS. During a period of free movement with aDBS, one patient reported a slight paresthesia; patients noticed no difference in treatment efficacy between systems. SIGNIFICANCE: Here is presented the first translation-ready training procedure for a fully embedded aDBS control system for MDs and one of the first examples of such a system in ET, adding to the consensus that fully implanted aDBS systems are sufficiently mature for broader deployment in treatment of movement disorders.

Deep Brain Stimulation for Spasmodic Dysphonia: A Blinded Comparison of Unilateral and Bilateral Stimulation in Two Patients.

Deep brain stimulation (DBS) is a promising new therapy for patients with spasmodic dysphonia (SD). The preliminary results from our randomized controlled trial showed good clinical effects with unilateral left thalamic stimulation in 6 right- handed patients. This suggests that the pathological process underpinning SD may have a "hemisphere dominant" pathway. We describe 2 patients with concurrent essential tremor and SD who had previously undergone bilateral thalamic DBS for their limb tremor. Both patients experienced an unanticipated improvement of their SD symptoms. One patient was right-handed, and the other was mixed left-handed. To investigate the amount of SD improvement following DBS therapy in each hemisphere, 4 different settings were tested: both sides on, left side on, right side on, and both sides off. Both patients most improved following bilateral stimulation. There was, however, a powerful unilateral benefit in both patients with only a small additional benefit from bilateral stimulation. The right-handed patient improved most with left-hemisphere stimulation whereas the mixed left-handed patient improved most with right hemisphere stimulation. There was some discrepancy between the two tests applied in the second patient reflecting the known difficulties to evaluate vocal symptom improvement in SD. We discuss the possible correlation of handedness and speech hemisphere dominance as well as the need for more reliable tests to measure SD severity. Ultimately, we recommend a bilateral approach for future studies, using a patient perception test as the primary outcome and functional imaging to further investigate the correlation of handedness and the amount of hemisphere dominance in SD.

Thalamic Deep Brain Stimulation for Essential Tremor: Relation of the Dentatorubrothalamic Tract with Stimulation Parameters.

BACKGROUND: In deep brain stimulation (DBS) for essential tremor, the primary target ventrointermedius (VIM) nucleus cannot be clearly visualized with structural imaging. As such, there has been much interest in the dentatorubrothalamic tract (DRTT) for target localization, but evidence for the DRTT as a putative stimulation target in tremor suppression is lacking. We evaluated proximity of the DRTT in relation to DBS stimulation parameters. METHODS: This is a retrospective analysis of 26 consecutive patients who underwent DBS with microelectrode recordings (46 leads). Fiber tracking was performed with a published deterministic technique. Clinically optimized stimulation parameters were obtained in all patients at the time of most recent follow-up (6.2 months). Volume of tissue activated (VTA) around contacts was calculated from a published model. RESULTS: Tremor severity was reduced in all treated hemispheres, with 70% improvement in the treated hand score of the Clinical Rating Scale for Tremor. At the level of the active contact (2.9 ± 2.0 mm superior to the commissural plane), the center of the DRTT was lateral to the contacts (5.1 ± 2.1 mm). The nearest fibers of the DRTT were 2.4 ± 1.7 mm from the contacts, whereas the radius of the VTA was 2.9 ± 0.7 mm. The VTA overlapped with the DRTT in 77% of active contacts. The distance from active contact to the DRTT was positively correlated with stimulation voltage requirements (Kendall τ = 0.33, P = 0.006), whereas distance to the atlas-based VIM coordinates was not. CONCLUSIONS: Active contacts in proximity to the DRTT had lower voltage requirements. Data from a large cohort provide support for the DRTT as an effective stimulation target for tremor control.

The effects of thalamic and posterior subthalamic deep brain stimulation on speech in patients with essential tremor - A prospective, randomized, doubleblind crossover study.

OBJECTIVE: To prospectively evaluate the effect of PSA- and VIM DBS on speech in ET patients. METHODS: Leads were implanted bilaterally with contacts placed in both VIM and PSA. Thirteen patients were analyzed pre- and postoperatively. Preoperative speech of ET patients was compared to healthy controls. PSA- and VIM-DBS were evaluated in a randomized, double-blind crossover phase. RESULTS: At preoperative baseline, we found reduced intelligibility. Differences in acoustic and VAS data ('ability to speak') compared to controls were gradient. Articulation rate could be predicted by disease duration. Decreased articulation rate, spirantization and voicing were found for PSA- and VIM-DBS. Targets did not differ in terms of speech deterioration. CONCLUSION: Speech in ET patients without DBS can be impaired, dependent on patient's individual characteristics. Both PSA- and VIM-DBS affect speech in a comparable way. Thus, the PSA can be considered an alternative DBS target in ET without higher risk of dysarthria.

Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor.

OBJECTIVE: To test the hypothesis that transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy is effective, durable, and safe for patients with medication-refractory essential tremor (ET), we assessed clinical outcomes at 3-year follow-up of a controlled multicenter prospective trial. METHODS: Outcomes were based on the Clinical Rating Scale for Tremor, including hand combined tremor-motor (scale of 0-32), functional disability (scale of 0-32), and postural tremor (scale of 0-4) scores, and total scores from the Quality of Life in Essential Tremor Questionnaire (scale of 0-100). Scores at 36 months were compared with baseline and at 6 months after treatment to assess for efficacy and durability. Adverse events were also reported. RESULTS: Measured scores remained improved from baseline to 36 months (all p < 0.0001). Range of improvement from baseline was 38%-50% in hand tremor, 43%-56% in disability, 50%-75% in postural tremor, and 27%-42% in quality of life. When compared to scores at 6 months, median scores increased for hand tremor (95% confidence interval [CI] 0-2, p = 0.0098) and disability (95% CI 1-4, p = 0.0001). During the third follow-up year, all previously noted adverse events remained mild or moderate, none worsened, 2 resolved, and no new adverse events occurred. CONCLUSIONS: Results at 3 years after unilateral tcMRgFUS thalamotomy for ET show continued benefit, and no progressive or delayed complications. Patients may experience mild degradation in some treatment metrics by 3 years, though improvement from baseline remains significant. CLINICALTRIALSGOV IDENTIFIER: NCT01827904. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years.

An Acute Randomized Controlled Trial of Noninvasive Peripheral Nerve Stimulation in Essential Tremor.

OBJECTIVE: To evaluate the safety and effectiveness of a wrist-worn peripheral nerve stimulation device in patients with essential tremor (ET) in a single in-office session. METHODS: This was a randomized controlled study of 77 ET patients who received either treatment stimulation (N = 40) or sham stimulation (N = 37) on the wrist of the hand with more severe tremor. Tremor was evaluated before and immediately after the end of a single 40-minute stimulation session. The primary endpoint compared spiral drawing in the stimulated hand using the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) Archimedes spiral scores in treatment and sham groups. Additional endpoints included TETRAS upper limb tremor scores, subject-rated tasks from the Bain and Findley activities of daily living (ADL) scale before and after stimulation as well as clinical global impression-improvement (CGI-I) rating after stimulation. RESULTS: Subjects who received peripheral nerve stimulation did not show significantly larger improvement in the Archimedes spiral task compared to sham but did show significantly greater improvement in upper limb TETRAS tremor scores (p = 0.017) compared to sham. Subject-rated improvements in ADLs were significantly greater with treatment (49% reduction) than with sham (27% reduction; p = 0.001). A greater percentage of ET patients (88%) reported improvement in the stimulation group as compared to the sham group (62%) according to CGI-I ratings (p = 0.019). No significant adverse events were reported; 3% of subjects experienced mild adverse events. CONCLUSIONS: Peripheral nerve stimulation in ET may provide a safe, well-tolerated, and effective treatment for transient relief of hand tremor symptoms.

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.

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.

Recent advances in Essential Tremor: Surgical treatment.

While no real breakthrough in the medical treatment of Essential Tremor (ET) has recently emerged, surgical field is expanding exponentially. Purpose of this review is to examine the recent and future developments of the surgical treatments for ET. Technological advances are shaping the present and the future application of deep brain stimulation (DBS) in ET. New electrode configurations as well as new implantable pulse generators are now available. Application of closed-loop or adaptive stimulation in clinical practice will allow DBS to deliver stimulation in a truly physiological way to restore aberrant neurological circuits on demand, thus avoiding side effects, tolerance and also saving the battery life. Besides DBS and standard thalamotomy, novel surgical approaches for ET are on the horizon. The development of MRI-guided focused ultrasound technique has been the new frontier of deep brain lesional therapies. Although the benefit of motor cortex stimulation is yet to be defined, this minimally invasive approach remains intriguing. Although the advances of surgical treatments along the clinical and technological directions described in this review will certainly contribute to a successful management of ET patients, future studies need to consider critical issues such as the heterogeneity of ET and the development of tolerance.

Sensory electrical stimulation for suppression of postural tremor in patients with essential tremor.

Essential tremor is an involuntary trembling of body limbs in people without tremor-related disease. In previous study, suppression of tremor by sensory electrical stimulation was confirmed on the index finger. This study investigates the effect of sensory stimulation on multiple segments and joints of the upper limb. It denotes the observation regarding the effect's continuity after halting the stimulation. 18 patients with essential tremor (8 men and 10 women) participated in this study. The task, "arms stretched forward", was performed and sensory electrical stimulation was applied on four muscles of the upper limb (Flexor Carpi Radialis, Extensor Carpi Radialis, Biceps Brachii, and Triceps Brachii) for 15 seconds. Three 3-D gyro sensors were used to measure the angular velocities of segments (finger, hand, and forearm) and joints (metacarpophalangeal and wrist joints) for three phases of pre-stimulation (Pre), during-stimulation (On), and 5 minute post-stimulation (P5). Three characteristic variables of root-mean-squared angular velocity, peak power, and peak power frequency were derived from the vector sum of the sensor signals. At On phase, RMS velocity was reduced from Pre in all segments and joints while peak power was reduced from Pre in all segments and joints except for forearm segment. Sensory stimulation showed no effect on peak power frequency. All variables at P5 were similar to those at On at all segments and joints. The decrease of peak power of the index finger was noted by 90% during stimulation from that of On phase, which was maintained even after 5 min. The results indicate that sensory stimulation may be an effective clinical method to treat the essential tremor.

Implementing novel trial methods to evaluate surgery for essential tremor.

INTRODUCTION: Deep brain stimulation (DBS) can provide dramatic essential tremor (ET) relief, however no Class I evidence exists. MATERIALS AND METHODS: Analysis methods: I) traditional cohort analysis; II) N-of-1 single patient randomised control trial and III) signal-to-noise (S/N) analysis. 20 DBS electrodes in ET patients were switched on and off for 3-min periods. Six pairs of on and off periods in each case, with the pair order determined randomly. Tremor severity was quantified with tremor evaluator and patient was blinded to stimulation. Patients also stated whether they perceived the stimulation to be on after each trial. RESULTS: I) Mean end-of-trial tremor severity 0.84 out of 10 on, 6.62 Off, t = - 13.218, p < 0.0005. II) N-of-1: 60% of cases had 12 correct perceptions (p = 0.001), 20% had 11 correct perceptions (p = 0.013). III) S/N: > 80% tremor reduction occurred in 99/114 'On' trials (87%), and 3/114 'Off' trials (3%). S/N ratio for 80% improvement with DBS versus spontaneous improvement was 487,757-to-1. CONCLUSIONS: DBS treatment effect on ET is too large for bias to be a plausible explanation. Formal N-of-1 trial design, and S/N ratio method for presenting results, allows this to be demonstrated convincingly where conventional randomised controlled trials are not possible. CLASSIFICATION OF EVIDENCE: This study is the first to provide Class I evidence for the efficacy of DBS for ET.

Morphometric and functional MRI changes in essential tremor with and without resting tremor.

The etiopathogenesis of essential tremor (ET) is still debated, since the predominant role of circuit dysfunction or brain degenerative changes has not been clearly established. The relationship with Parkinson's Disease (PD) is also controversial and resting tremor occurs in up to 20 % of ET. We investigated the morphological and functional changes associated with ET and we assessed potential differences related to the presence (ET+R) or absence (ET-R) of resting tremor. 32 ET patients (18 ET+R; 14 ET-R) and 12 healthy controls (HC) underwent 3T-MRI protocol including Spoiled Gradient T1-weighted sequence for Voxel-Based Morphometry (VBM) analysis and functional MRI during continuous writing of "8" with right dominant hand. VBM analysis revealed no gray and white matter atrophy comparing ET patients to HC and ET+R to ET-R patients. HC showed a higher BOLD response with respect to ET patients in cerebellum and other brain areas pertaining to cerebello-thalamo-cortical circuit. Between-group activation maps showed higher activation in precentral gyrus bilaterally, right superior and inferior frontal gyri, left postcentral gyrus, superior and inferior parietal gyri, mid temporal and supramarginal gyri, cerebellum and internal globus pallidus in ET-R compared to ET+R patients. Our findings support that the dysfunction of cerebello-thalamo-cortical network is associated with ET in absence of any morphometric changes. The dysfunction of GPi in ET+R patients, consistently with data reported in PD resting tremor, might suggest a potential role of this structure in this type of tremor.

Functional assessment and quality of life in essential tremor with bilateral or unilateral DBS and focused ultrasound thalamotomy.

BACKGROUND: Thalamic deep brain stimulation (DBS) has largely replaced radiofrequency thalamotomy as the treatment of choice for disabling, medication-refractory essential tremor. Recently, the development of transcranial, high-intensity focused ultrasound has renewed interest in thalamic lesioning. The purpose of this study is to compare functional outcomes and quality of life in essential tremor patients treated with either bilateral Vim DBS or unilateral procedures (focused ultrasound or DBS). We hypothesized that all three would effectively treat the dominant hand and positively impact functional outcomes and quality of life as measured with the Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire. METHODS: This is a retrospective study of medication-refractory essential tremor patients treated at the University of Virginia with bilateral Vim DBS (n = 57), unilateral Vim DBS (n = 13), or unilateral focused ultrasound Vim thalamotomy (n = 15). Tremor was rated for all patients before and after treatment, using the Clinical Rating Scale for Tremor and Quality of Life in Essential Tremor Questionnaire. RESULTS: Patients undergoing bilateral DBS treatment had more baseline tremor and worse quality of life scores. Patients had significant improvements in tremor symptoms and quality of life with all three treatments. Both DBS procedures improved axial tremor. No difference was seen in the degree of improvement in upper extremity tremor score, disability, or overall quality of life between bilateral and either unilateral procedure. CONCLUSIONS: Bilateral thalamic DBS improves overall tremor more than unilateral DBS or focused ultrasound treatment; however, unilateral treatments are equally effective in treating contralateral hand tremor. Despite the greater overall tremor reduction with bilateral DBS, there is no difference in disability or quality of life comparing bilateral versus unilateral treatments.

Thalamomuscular coherence in essential tremor: hen or egg in the emergence of tremor?

Thalamomuscular coherence in essential tremor (ET) has consistently been detected in numerous neurophysiological studies. Thereby, spatial properties of coherence indicate a differentiated, somatotopic organization; so far, however, little attention has been paid to temporal aspects of this interdependency. Further insight into the relationship between tremor onset and the onset of coherence could pave the way to more efficient deep brain stimulation (DBS) algorithms for tremor. We studied 10 severely affected ET patients (six females, four males) during surgery for DBS-electrode implantation and simultaneously recorded local field potentials (LFPs) and surface electromyographic signals (EMGs) from the extensor and flexor muscles of the contralateral forearm during its elevation. The temporal relationship between the onset of significant wavelet cross spectrum (WCS) and tremor onset was determined. Moreover, we examined the influence of electrode location within one recording depth on this latency and the coincidence of coherence and tremor for depths with strong overall coherence ("tremor clusters") and those without. Data analysis revealed tremor onset occurring 220 ± 460 ms before the start of significant LFP-EMG coherence. Furthermore, we could detect an anterolateral gradient of WCS onset within one recording depth. Finally, the coincidence of tremor and coherence was significantly higher in tremor clusters. We conclude that tremor onset precedes the beginning of coherence. Besides, within one recording depth there is a spread of the tremor signal. This reflects the importance of somatosensory feedback for ET and questions the suitability of thalamomuscular coherence as a biomarker for "closed-loop" DBS systems to prevent tremor emergence.