Influence of age, gender and severity of tremor on outcome after thalamic and subthalamic DBS for essential tremor

Deep brain stimulation (DBS) is an established treatment for essential tremor (ET). The nucleus ventralis intermedius thalami (Vim) is the target of choice, but promising results have been presented regarding DBS in the posterior subthalamic area (PSA). The aim of this study was to evaluate the possible influence of gender, age and severity of disease on the outcome of these procedures.Sixty eight patients (34 Vim, 34 PSA) with ET were included in this non-randomised study. Evaluation using the Essential Tremor Rating Scale (ETRS) was performed before, and one year after surgery concerning PSA DBS, and at a mean of 28 ± 24 months concerning Vim DBS. Items 5/6 and 11–14 (hand tremor and hand function) were selected for analysis of tremor outcome.The efficacy of DBS on essential tremor was not related to age or gender. Nor was it associated with the severity of tremor when the percentual reduction of tremor on stimulation was taken into account. However, patients with a more severe tremor at baseline had a higher degree of residual tremor on stimulation. Tremor in the treated hand and hand function were improved with 70% in the Vim group and 89% in the PSA group.     

Effects of Electrode Implantation Angle on Thalamic Stimulation for Treatment of Tremor

Introduction. Chronic thalamic stimulation has been confirmed as an effective treatment for tremor. The optimal target has been commonly accepted to be situated within the ventral thalamus, but a standard trajectory of the deep brain stimulation (DBS) electrode has not yet been established. Materials and Methods. A 53‐year‐old man with an 11‐year history of essential tremor was treated by DBS of the thalamus. In this patient, we had a chance to compare the effects of different trajectory angles of the DBS electrode on tremor. Results. Intraoperative stimulation with the DBS electrode temporarily inserted at a high angle to the horizontal plane of the anterior commissure–posterior commissure (AC–PC) line to cover only the nucleus ventralis intermedius (Vim) was not effective. In contrast, stimulation with the DBS electrode permanently implanted at a low angle, covering a wide area extending from the nucleus ventralis oralis (Vo) to the Vim, reduced the tremor. Conclusion. We report on the case of a patient who showed different effects on tremor depending on the trajectory angle of the DBS electrode to the AC–PC line. The insertion trajectory of the DBS electrode may be an important factor for the treatment of tremor.     

Objective tremor registration during DBS surgery for Essential Tremor

Essential Tremor (ET) is characterized by a 4–12-Hz postural and kinetic tremor, most commonly affecting the upper limbs. Deep brain stimulation (DBS) of the thalamus (Vim) has been found to be highly effective in severe/refractory forms of ET. Intra-operative assessment of tremor is performed using clinical methods based on patient and physician perception of tremor intensity. We present for the first time the case of a patient whose tremor was objectively monitored/quantified pre- and intra-operatively using device-based tremor registration to supplement clinical measures.     

Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation.

OBJECTIVE: To compare the effects of unilateral subthalamic nucleus (STN) deep brain stimulation (DBS) with bilateral STN DBS in advanced PD. METHODS: Our initial 10 consecutive patients with medication-refractory motor fluctuations and levodopa-induced dyskinesias undergoing chronic bilateral STN DBS underwent a standardized evaluation of unilateral and bilateral STN DBS in the medication-off state 6 to 18 months after electrode implantation. RESULTS: Bilateral STN DBS improved the mean total Unified Parkinson's Disease Rating Scale motor score by 54%, whereas unilateral stimulation improved motor scores only 23%. Unilateral STN DBS improved postural stability and gait 14%, other axial motor features 19%, and overall parkinsonism in limbs contralateral to stimulation by 46%, including an 86% improvement in contralateral tremor. However, bilateral STN DBS resulted in greater improvement in each of these domains, including limb function, i.e., the reduction in scores from the limbs on one side was greater with bilateral than with unilateral stimulation of the contralateral STN. CONCLUSIONS: Bilateral STN DBS improves parkinsonism considerably more than unilateral STN DBS; bilateral simultaneous electrode implantation may be the most appropriate surgical option for patients with significant bilateral disability. Unilateral STN DBS results in moderate improvement in all aspects of off-period parkinsonism and improves tremor as much as is typically reported with DBS of the ventral intermedius nucleus of the thalamus (Vim). For this reason, STN DBS may be a more appropriate choice than Vim DBS or thalamotomy for parkinsonian tremor. Some patients with highly asymmetric tremor-dominant PD might be appropriately treated with unilateral instead of bilateral STN DBS.     

Loss of benefit in VIM thalamic deep brain stimulation (DBS) for essential tremor (ET): How prevalent is it?

Ventralis intermedius (Vim) thalamic deep brain stimulation for medication-refractory essential tremor (ET) has been shown to significantly improve severity of limb tremor in several large case series with significant reduction in objective motor scores. A variable proportion of patients experience decline in benefit over time, however, most studies have not been designed to describe the phenomenon of waning benefit in terms that are helpful for patient counseling. In this retrospective single center study, we define waning benefit as a phenomenon that occurs after patients begin to require reprogramming visits to optimize DBS benefit on tremor. We employed a survival analysis with time to escape (TTE) as a quantitative measure of time elapsed between implantation and the need for subsequent reprogramming. In our cohort of ET patients operated on with Vim DBS from 1994 to 2009, among 45 subjects who met inclusion criteria, 73% reported waning benefit at some point during a mean follow-up period of 56 months (range 12–152 months). The mean TTE from implantation date was 18 months (range 3–75 months). We conclude that loss of benefit over time from Vim DBS for ET is more prevalent than previously published estimates have indicated and should be discussed during patient counseling regarding durability of expected benefit. In addition, this data suggests that a disease-based explanation rather than technical factors are more likely to explain the decline in benefit.     

Mood and motor effects of thalamic deep brain stimulation surgery for essential tremor

Purpose: The aim of this study was to evaluate the effects of unilateral and bilateral ventralis intermedius (Vim) deep brain stimulation (DBS) on mood and motor function. Methods: Thirty‐one consecutive medication refractory patients with essential tremor who underwent unilateral or bilateral Vim DBS at University of Florida and returned for at least 6 ‐month follow‐up completed the Visual Analog Mood (VAMS), the Beck Depression Inventory (BDI), and the Tremor Rating Scale (TRS) before and after surgery. We excluded all patients who were implanted at other institutions. Results: The tense subscale of the VAMS improved significantly in both the unilateral and bilateral DBS groups (P < 0.001). On the VAMS afraid subscale, only the bilateral group trended toward improvement (P = 0.075). There were no significant changes for either group for the happy, confused, sad, angry, energetic or tired VAMS scores. TRS subscale scores all improved after unilateral and bilateral Vim DBS surgery (P < 0.001). Conclusions: Feelings of tenseness, tremor severity and ADLs improved following unilateral or bilateral Vim DBS for ET.     

Bilateral effects of unilateral thalamic deep brain stimulation: A case report

A recent study has proved that unilateral deep brain stimulation (DBS) of the subthalamic nucleus has bilateral effects. However, it is still unclear whether unilateral ventral intermediate thalamic nucleus (Vim) DBS exerts exclusively contralateral or bilateral effects on tremor. Previous studies demonstrated a clinically irrelevant improvement on the nontarget side after thalamic stimulator implantation, which was considered to be solely the result of mechanical effects. We report here the case of a 55‐year‐old woman in whom unilateral thalamic DBS can stop the disabling postural‐kinetic tremor in both hands. Simultaneous surface electromyography (sEMG), accelerometry, and video recordings were obtained to evaluate the underlying mechanism. After the right Vim DBS was turned off, moderate rest tremor appeared in both hands accompanied by bilateral bursts on sEMG. Because right hand tremor cannot simply reflect the mechanical overflow of the left side, the bilateral improvement caused by right Vim DBS is probably due to an active tremor reduction in this particular case. © 2007 Movement Disorder Society     

Central oscillators in a patient with neuropathic tremor: Evidence from intraoperative local field potential recordings

Present pathophysiological concepts of neuropathic tremor assume mistimed and defective afferent input resulting in deregulation of cerebello‐thalamo‐cortical motor networks. Here, we provide direct evidence of central tremor processing in a 76‐year‐old female who underwent bilateral deep brain stimulation of the ventral intermedial nucleus of the thalamus (Vim‐DBS) because of neuropathic tremor associated with IgM paraproteinemia. Electrophysiological recordings of EEG and EMG were performed in three perioperative sessions: (1) preoperatively, (2) intraoperatively, and (3) 4 days after surgery in both rest and postural tremor conditions. Tremor‐related synchronization (coherence) between motor cortex (M1) and muscles (M. extensor digitorum, M. flexor digitorum) was assessed, and additional intraoperative local field potential (LFP) recordings from Vim allowed comprehensive coherence mapping in thalamo‐cortico‐muscular networks. Directionality of information flow was determined by directed transfer function (DTF) and phase analyses. Stimulation effects on tremor and corticomuscular coherence were assessed and the patient was followed for 12 months on clinical outcome measures (Tremor Rating Scale, CADET‐Score). Vim‐DBS reduced tremor (59%) and improved motor functionality in daily activities (31%, CADET‐A) after 12 months. Intraoperative recordings demonstrated significant coherence in the tremor frequency (4 Hz) between M1 and contralateral muscle, Vim and ipsilateral M1, Vim and contralateral muscle, but not between Vim and contralateral M1. Information flow was directed from M1 to Vim and bidirectional between M1 and muscle and between Vim and muscle, respectively. Corticomuscular coherence at tremor frequency was completely suppressed by Vim‐DBS. Our case study demonstrates central oscillators underlying neuropathic tremor and implies a strong pathophysiological rationale for Vim‐DBS. © 2010 Movement Disorder Society     

Thalamic deep brain stimulation in the treatment of essential tremor

Background and purposeQuality of life can be severely impaired by essential tremor (ET) being the main cause of the patient's disability. The authors present a group of ET patients treated with deep brain stimulation of the ventral intermediate nucleus of the thalamus (Vim DBS). The aim of the study was to evaluate the efficacy and safety of Vim DBS in the treatment of ET.Material and methodsBetween 2006 and 2009, 8 female and 10 male ET patients were treated with Vim DBS. Mean age at implantation was 63 ± 15 years. ET lasted from 4 to 30 years (mean 12 years). Clinical condition of the group was evaluated before surgery and 3 months after implantation with spirography (spiral drawings), the modified Fahn (Tremor Rating Scale, TRS) scale, and the modified ADL (Activity of Daily Living) scale. The Vim was localized with CT and MRI. The procedures of implantation were performed under local and general anaesthesia. A bilateral procedure was performed in 11 cases and a unilateral procedure was performed in 7 cases.ResultsThe therapeutic effect of DBS was maintained at the follow-up in the third month following surgery. Mean contralateral limb tremor reduction was 79%. Head tremor reduction was reported by 75% of patients in the bilateral Vim DBS subgroup and 50% of patients in the unilateral Vim DBS subgroup. Mean ADL score improved by 61%.ConclusionsVim DBS is a safe and effective method of ET treatment. Vim DBS improves activities of daily living of ET patients.     

Steady or not following thalamic deep brain stimulation for essential tremor

Deep brain stimulation (DBS) has become an important option for medication-refractory essential tremor (ET), but may contribute to worsened gait and falling. This study evaluates impaired gait in a cohort of patients treated with DBS with a retrospective review of ET patients before and after DBS implantation. Factors examined included: age, duration of symptoms, pre-morbid gait difficulties/falls, Fahn-Tolosa-Marin tremorrating scale (TRS) scores at baseline, 6 months post-unilateral DBS implantation, and 6 or 12 months post-bilateral implantation. All implantations targeted the nucleus ventralis intermediate (Vim). Thirty-eight patients (25 males, 13 females) were included. Twenty-five patients (65.8%) underwent unilateral DBS implantation and 13 (34.2%) bilateral. The mean age at surgery was 67.1 years ± 11.4 (range 34-81). The mean disease duration was 31 years ± 18.3 (range 6-67). Fifty-eight percent of patients had worsened gait post-operatively. Seventy percent of patients with unilateral Vim DBS experienced gait worsening while 55% of bilateral DBS patients experienced gait worsening. Patients with worsened gait post-DBS had higher baseline pre-operative TRS scores than those without worsened gait (43.1 points ± 8.4 vs. 33.1 points ± 10.1, p = 0.002) (odds ratio 2.5, p = 0.02). Gait/balance may worsen following DBS for medication refractory ET. Higher baseline TRS score may factor into these issues, although a larger prospective study will be required with a control population. The larger percentage of difficulties observed in unilateral versus bilateral cases likely reflected the bias not to proceed to second-sided surgery if gait/balance problems were encountered.     

Deep brain stimulation of the ventral intermediate nucleus of the thalamus in medically refractory orthostatic tremor: Preliminary observations

Orthostatic tremor (OT) is a disabling movement disorder associated with postural and gait impairment in the elderly. Medical therapy often yields insufficient benefit. We report the clinical and electrophysiological data on two patients with medication‐refractory OT treated with deep brain stimulation of the ventral intermediate thalamic nucleus (Vim DBS). Patient 1 underwent bilateral deep brain stimulation (DBS) and Patient 2 unilateral Vim DBS following 28 and 30 years of disease duration, respectively. Both patients showed increased latency to symptom onset after rising from a seated position, improved tolerance for prolonged standing, and slower crescendo of tremor severity when remaining upright. Postoperative evaluation demonstrated decreased amplitude of electromyographic activity with persistence of well‐defined oscillatory behavior showing strong coherence at 15 Hz between all muscles tested in the upper and lower limbs. Postural sway was unchanged. Clinical benefits have been sustained for over 18 months in Patient 1, and receded after 3 months in Patient 2. These findings support the consideration of bilateral Vim DBS implantation as a therapeutic option in patients with medically refractory OT. Further efficacy studies on chronic stimulation to disrupt the abnormal oscillatory activity in this disorder are warranted. © 2008 Movement Disorder Society     

Combined deep brain stimulation and thalamotomy for tremor-dominant Parkinson’s disease

Although deep brain stimulation (DBS) is an established treatment for Parkinson’s disease, the long-term suppression of tremor is still a challenging issue. We report two patients with tremor-dominant Parkinson’s disease (PD) treated with unilateral thalamotomy of the ventralis intermedius nucleus (Vim) combined with the subthalamic nucleus (STN)-DBS or the posterior subthalamic area (PSA)-DBS. One year after the surgery, thalamotomy of the area from the Vim to the PSA showed improvement not only in tremor but also in rigidity and akinesia. PSA- or STN-DBS with low intensity stimulation eliminated residual PD symptoms. Combined DBS and thalamotomy may provide long-term improvement of the majority of PD symptoms using lower therapeutic stimulation voltages.     

脑深部电刺激治疗帕金森病和特发性震颤的近期和远期疗效

自1987年以后,脑深部电刺激(deep brain stimulation,DBS)成为治疗难治性帕金森病和特发性震颤的主要外科手段。刺激的靶点最先为丘脑腹侧中间核(nucleus ventero-intermedius,Vim)。由于Vim DBS只能缓解震颤,而对于帕金森病的其他核心症状以及多巴长期应用后的不良反应,如运动波动和异动症疗效不显著,1990年后治疗PD的靶点转移到丘脑底核(subthalamic nucleus,STN)和苍白球内侧部(interal globus pallidus,GPi),上述问题在这两个靶点得到显著改善。Vim DBS仍然为治疗特发性震颤的位点。本文就这3个靶点的持续电刺激在治疗帕金森病和特发性震颤的近期和远期疗效等进行评述。     

Deep brain stimulation in the posterior subthalamic area in the treatment of essential tremor

To evaluate the posterior subthalamic area (PSA) as a target for deep brain stimulation (DBS) in the treatment of essential tremor (ET). The ventral intermediate nucleus of the thalamus is the traditional target for DBS in the treatment of ET. Recent studies have presented beneficial effects of DBS in the PSA in the treatment of tremor. Twenty‐one patients with ET were included in this study. All patients were evaluated before and 1 year after surgery, on and off stimulation, using the essential tremor rating scale (ETRS). A marked microlesional effect was noticed in 83%, in some cases obviating the need for electrical stimulation for many months. The total ETRS was reduced from 46.2 at baseline to 18.7 (60%). Item 5/6 (tremor of the upper extremity) was improved from 6.2 to 0.3 (95%), and items 11 to 14 (hand function) from 9.7 to 1.3 (87%) concerning the contralateral hand. Activities of daily living were improved by 66%. No severe complication occurred. Eight patients presented a postoperative mild dysphasia that regressed within days to weeks. DBS in the PSA resulted in a marked reduction of tremor. © 2010 Movement Disorder Society     

Deep brain stimulation of the ventral intermediate thalamic nucleus in the treatment of essential tremor

Essential tremor (ET) is the most common movement disorder. In most patients the course of ET is mild and pharmacological therapy controls postural and kinetic components of tremor. The first-line treatment of ET is pharmacotherapy with propranolol, primidone and gabapentin. In patients with marked head and voice tremor, local botulinum toxin injections have been found to be very effective. Despite optimal drug therapies it is estimated that approximately 50% of patients with ET have medication-resistant tremor. ET can cause more functional impairment than parkinsonian resting tremor because most prominent components of ET are postural and kinetic ones. For patients with drug-resistant debilitating tremor, surgical therapy (thalamotomy) and more recently deep brain stimulation (DBS) of the ventral intermediate thalamic nucleus (VIM) is a viable treatment modality. Several long-term studies have confirmed the high effectiveness rate of ablative surgery and thalamic DBS in the treatment of ET. The most striking advantage of thalamic DBS is the possibility of performing bilateral surgery in one operative session with a significantly lower rate of side effects. Nowadays the bilateral staged thalamotomy is performed rarely because of unacceptable side effects. Moreover, many authors have observed that in bilaterally stimulated patients the head and voice tremor have diminished in postoperative course. Thalamic DBS is a very efficacious and safe procedure in the treatment of ET.     

Thalamic deep brain stimulation: comparison between unilateral and bilateral placement

BACKGROUND: Unilateral thalamic deep brain stimulation (DBS) is accepted as an effective treatment for essential tremor (ET) and the tremor of Parkinson disease (PD). There are, however, relatively little data concerning bilateral thalamic DBS and no thorough comparisons between the 2 methods. METHODS: To assess the relative benefit of a staged second contralateral DBS placement in patients with PD and ET, we compared preoperative baseline assessments with those at 3 months after the initial implantation, and again at 3 months after the second contralateral implantation. The assessments included the Unified Parkinson's Disease Rating Scale for patients with PD (n = 8) and a modified Unified Tremor Rating Assessment for patients with ET (n = 13). The design included open and blinded (unknown activation status) assessments. RESULTS: Overall, after the second implantation, all specific measures assessing tremor contralateral to that side improved in patients with PD and ET, generally without sacrificing those contralateral to the first side implantation. Midline tremors (face and head) improved only after the second side implantation. In patients with ET, functional and subjective scores tended to further improve after the second placement; however, patients with PD had less subjective improvement. Hand tremor scores in patients with ET randomized to "on" stimulation improved from 6.7 +/- 0.9 to 1.3 +/- 1.2 (P<.005). The scores of patients with PD randomized to on stimulation improved from 9.3 +/- 1.0 to 1.0 +/- 0.5. (Data are given as mean +/- SD.) Tremor scores did not change from baseline in those patients randomized to "off" stimulation in either group. Adverse events related to stimulation increased after the second implantation in both groups. CONCLUSIONS: Bilateral thalamic DBS is more effective than unilateral DBS at controlling bilateral appendicular and midline tremors of ET and PD. Despite this, overall functional disability only improved in patients with ET, possibly secondary to more problematic adverse events in patients with PD, especially balance problems. Bilateral DBS should be considered when unilateral DBS does not offer satisfactory benefit, especially in patients with ET.     

Successful thalamic deep brain stimulation for orthostatic tremor

We report a patient with severe orthostatic tremor (OT) unresponsive to pharmacological treatments that was successfully controlled with thalamic (Vim, ventralis intermedius nucleus) deep brain stimulation (DBS) over a 4‐year period. Cortical activity associated with the OT revealed by EEG back‐averaging and fluoro‐deoxi‐glucose PET were also suppressed in parallel with tremor arrest. This case suggests that Vim‐DBS may be a useful therapeutic approach for patients highly disabled by OT. © 2008 Movement Disorder Society     

Gait and balance in essential tremor: Variable effects of bilateral thalamic stimulation

Essential tremor (ET) is a multi‐faceted condition best known for postural and action tremor but also may include disordered gait and postural instability. Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus provides substantial tremor reduction yet some patients with bilateral VIM DBS have gait and balance impairment. This study examines gait and balance performance in 13 participants with ET who have bilateral VIM DBS compared with a matched control group. Participants with ET were tested with their stimulators off (DBS OFF) and on (DBS ON). For both standard and tandem walking, participants with ET walked significantly more slowly than controls, with significantly lower cadence, spending a lower percentage of the gait cycle in single limb support and a higher percentage in double support compared with controls. Participants with ET also had significantly lower tandem and one leg stance times, Berg balance scores, balance confidence, and required significantly greater time to perform the Timed Up‐and‐Go relative to controls. There were no significant differences in any gait or balance measures in the DBS OFF versus DBS ON conditions, but the effects of DBS on gait and balance were highly variable among individuals. Future studies are needed to determine why some individuals experience gait and balance difficulties after bilateral thalamic DBS and others do not. A better understanding of the mechanisms underlying gait and balance impairments in those with bilateral DBS is critical to reduce falls and fractures in this group. © 2008 Movement Disorder Society     

Comparing Two Deep Brain Stimulation Leads to One in Refractory Tremor

A sizable proportion of medication refractory tremor patients may not respond satisfactorily to deep brain stimulation (DBS) to the ventralis intermedialis nucleus of the thalamus (Vim). Implanting a second DBS lead ipsilaterally to the first one is thought to be beneficial based on scarce and unblinded data. This article aims to report a double-blind assessment of five patients with a second DBS lead for refractory tremor. Tremor was assessed by two blinded movement disorder specialists using a videotaped tremor rating scale (TRS) evaluation of each patient in four conditions: both leads OFF, Vim ON/2nd lead OFF, Vim OFF/2nd lead ON, and both leads ON. Paired t-test was used to determine if double stimulation was different than stimulation of Vim alone or than stimulation of the 2nd lead alone. Each hypothesis was tested with the total TRS as well as the contralateral upper limb score and the contralateral hemibody score. Tremor was secondary to multiple sclerosis in two patients and to essential tremor in three. The second lead was in the ventralis oralis anterior nucleus of the thalamus in three patients and in the prelemniscal radiations in two patients. There was improvement with the 2nd lead or double ON in four patients compared to stimulating the Vim alone. However, when taken as a group, the results were not statistically significant. These results were constant with the three different ratings used. The lack of overall statistically significant improvement might be secondary to the small size and the heterogeneity of our sample. However, four patients had 17 to 60 % tremor improvement after the implant of the 2nd lead on double-blinded evaluation. We report objective improvement after addition of a second DBS lead in patients with tremor refractory to Vim DBS. Larger studies are needed to confirm these results.     

Decoding voluntary movements and postural tremor based on thalamic LFPs as a basis for closed-loop stimulation for essential tremor

BackgroundHigh frequency Deep brain stimulation (DBS) targeting motor thalamus is an effective therapy for essential tremor (ET). However, conventional continuous stimulation may deliver unnecessary current to the brain since tremor mainly affects voluntary movements and sustained postures in ET.ObjectiveWe aim to decode both voluntary movements and the presence of postural tremor from the Local field potentials (LFPs) recorded from the electrode implanted in motor thalamus for stimulation, in order to close the loop for DBS so that stimulation could be delivered on demand, without the need for peripheral sensors or additional invasive electrodes.MethodsLFPs from the motor thalamus, surface electromyographic (EMG) signals and/or behavioural measurements were simultaneously recorded in seven ET patients during temporary lead externalisation 3–5 days after the first surgery for DBS when they performed different voluntary upper limb movements. Nine different patients were recorded during the surgery, when they were asked to lift their arms to trigger postural tremor. A machine learning based binary classifier was used to detect voluntary movements and postural tremor based on features extracted from thalamic LFPs.ResultsCross-validation demonstrated that both voluntary movements and postural tremor can be decoded with an average sensitivity of 0.8 and false detection rate of 0.2. Oscillatory activities in the beta frequency bands (13–23 Hz) and the theta frequency bands (4–7 Hz) contributed most to the decoding of movements and postural tremor, respectively, though incorporating features in different frequency bands using a machine learning approach increased the accuracy of decoding.