Unilateral Thalamic Deep Brain Stimulation Research Articles

Enhancing outcomes in deep brain stimulation: a comparative study of direct targeting using 7T versus 3T MRI.

The aim of this study was to compare outcomes of direct targeting in deep brain stimulation (DBS) for essential tremor using 7T MRI versus 3T MRI. The authors hypothesized that 7T MRI direct targeting would be noninferior to 3T MRI in early tremor outcomes. A retrospective study was conducted on patients undergoing unilateral thalamic DBS for essential tremor between 2021 and 2023. Two matched cohorts were assessed, one using 7T MRI and the other using 3T MRI for surgical planning. The primary endpoint was the percentage improvement in the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) scores. Additionally, the authors assessed optimized programming settings and variance in electrode position on postoperative imaging. Demographic and clinical data were compared using the nonparametric Mann-Whitney U-test. The squared Euclidean distance of each contact from the group mean centroid was calculated and averaged across the entire cohort to provide the variance (i.e., the mean squared distance) of electrode contact position. A total of 34 patients were analyzed, with 17 in each cohort. There were no significant differences in demographic information or mean surgical dates between the groups. There were no differences in intraoperative target repositioning or adverse events. The 7T group had a significantly greater TRS improvement than the 3T group (64.9% ± 11.4% vs 50.9% ± 16.4%, p = 0.004). Patients in the 7T cohort also had a lower mean stimulation current compared with those in the 3T cohort (2.0 ± 0.8 mA vs 2.7 ± 0.9 mA, p = 0.01). Image evaluation revealed that although the mean electrode position was comparable between 7T and 3T, the 7T electrode positioning was more clustered, indicating a lower variance in the final electrode location. The mean Euclidean distance between the individual electrode tips and the group centroid was significantly less at 7T than at 3T (1.82 ± 0.68 mm vs 2.75 ± 0.81 mm, p = 0.001). Despite concerns for increased artifacts and distortions at 7T, the authors show that these effects can be mitigated with an appropriate workflow, leading to improved surgical outcomes with direct targeting using 7T MRI. Their results suggest similar accuracy but greater precision in targeting with 7T MRI compared with 3T MRI, resulting in lower stimulation currents and improved tremor reduction. Future studies are needed to assess outcomes related to 7T MRI in targeting other subcortical structures.

Treatment of Chronic Refractory Pain by Combined Deep Brain Stimulation of the Anterior Cingulum and Sensory Thalamus (EMOPAIN Study): Rationale and Protocol of a Feasibility and Safety Study

Background: Deep Brain Stimulation (DBS) of the sensory thalamus has been proposed for 40 years to treat medically refractory neuropathic pain, but its efficacy remains partial and unpredictable. Recent pilot studies of DBS targeting the ACC, a brain region involved in the integration of the affective, emotional, and cognitive aspects of pain, may improve patients suffering from refractory chronic pain. ACC-DBS could be complementary to thalamic DBS to treat both the sensory-discriminative and the affective components of chronic pain, but the safety of combined DBS, especially on cognition and affects, has not been studied. Methods: We propose a prospective, randomized, double-blind, and bicentric study to evaluate the feasibility and safety of bilateral ACC-DBS combined with unilateral thalamic DBS in adult patients suffering from chronic unilateral neuropathic pain, refractory to medical treatment. After a study period of six months, there is a cross-over randomized phase to compare the efficacy (evaluated by pain intensity and quality of life) and safety (evaluated by repeated neurological examination, psychiatric assessment, cognitive assessment, and assessment of affective functions) of combined ACC-thalamic DBS and thalamic DBS only, respectively. Discussion: The EMOPAIN study will show if ACC-DBS is a safe and effective therapy for patients suffering from chronic unilateral neuropathic pain, refractory to medical treatment. The design of the study will, for the first time, assess the efficacy of ACC-DBS combined with thalamic DBS in a blinded way.

Comparative connectivity correlates of dystonic and essential tremor deep brain stimulation

The pathophysiology of dystonic tremor and essential tremor remains partially understood. In patients with medication-refractory dystonic tremor or essential tremor, deep brain stimulation (DBS) targeting the thalamus or posterior subthalamic area has evolved into a promising treatment option. However, the optimal DBS targets for these disorders remains unknown. This retrospective study explored the optimal targets for DBS in essential tremor and dystonic tremor using a combination of volumes of tissue activated estimation and functional and structural connectivity analyses. We included 20 patients with dystonic tremor who underwent unilateral thalamic DBS, along with a matched cohort of 20 patients with essential tremor DBS. Tremor severity was assessed preoperatively and approximately 6 months after DBS implantation using the Fahn-Tolosa-Marin Tremor Rating Scale. The tremor-suppressing effects of DBS were estimated using the percentage improvement in the unilateral tremor-rating scale score contralateral to the side of implantation. The optimal stimulation region, based on the cluster centre of gravity for peak contralateral motor score improvement, for essential tremor was located in the ventral intermediate nucleus region and for dystonic tremor in the ventralis oralis posterior nucleus region along the ventral intermediate nucleus/ventralis oralis posterior nucleus border (4 mm anterior and 3 mm superior to that for essential tremor). Both disorders showed similar functional connectivity patterns: a positive correlation between tremor improvement and involvement of the primary sensorimotor, secondary motor and associative prefrontal regions. Tremor improvement, however, was tightly correlated with the primary sensorimotor regions in essential tremor, whereas in dystonic tremor, the correlation was tighter with the premotor and prefrontal regions. The dentato-rubro-thalamic tract, comprising the decussating and non-decussating fibres, significantly correlated with tremor improvement in both dystonic and essential tremor. In contrast, the pallidothalamic tracts, which primarily project to the ventralis oralis posterior nucleus region, significantly correlated with tremor improvement only in dystonic tremor. Our findings support the hypothesis that the pathophysiology underpinning dystonic tremor involves both the cerebello-thalamo-cortical network and the basal ganglia-thalamo-cortical network. Further our data suggest that the pathophysiology of essential tremor is primarily attributable to the abnormalities within the cerebello-thalamo-cortical network. We conclude that the ventral intermediate nucleus/ventralis oralis posterior nucleus border and ventral intermediate nucleus region may be a reasonable DBS target for patients with medication-refractory dystonic tremor and essential tremor, respectively. Uncovering the pathophysiology of these disorders may in the future aid in further improving DBS outcomes.

Gait worsening and the microlesion effect following deep brain stimulation for essential tremor

ObjectiveTo investigate the effects of unilateral thalamic deep brain stimulation (DBS) on walking in persons with medication-refractory essential tremor (ET).MethodsWe performed laboratory-based gait analyses on 24 persons with medication-refractory ET...

The effect of unilateral thalamic deep brain stimulation on the vocal dysfunction in a patient with spasmodic dysphonia: interrogating cerebellar and pallidal neural circuits

Spasmodic dysphonia (SD) is a neurological disorder of the voice where a patient's ability to speak is compromised due to involuntary contractions of the intrinsic laryngeal muscles. Since the 1980s, SD has been treated with botulinum toxin A (BTX) injections into the throat. This therapy is limited by the delayed-onset of benefits, wearing-off effects, and repeated injections required every 3 months. In a patient with essential tremor (ET) and coincident SD, the authors set out to quantify the effects of thalamic deep brain stimulation (DBS) on vocal function while investigating the underlying motor thalamic circuitry. A 79-year-old right-handed woman with ET and coincident adductor SD was referred to our neurosurgical team. While primarily treating her limb tremor, the authors studied the effects of unilateral, thalamic DBS on vocal function using the Unified Spasmodic Dysphonia Rating Scale (USDRS) and voice-related quality of life (VRQOL). Since dystonia is increasingly being considered a multinodal network disorder, an anterior trajectory into the left thalamus was deliberately chosen such that the proximal contacts of the electrode were in the ventral oralis anterior (Voa) nucleus (pallidal outflow) and the distal contacts were in the ventral intermediate (Vim) nucleus (cerebellar outflow). In addition to assessing on/off unilateral thalamic Vim stimulation on voice, the authors experimentally assessed low-voltage unilateral Vim, Voa, or multitarget stimulation in a prospective, randomized, doubled-blinded manner. The evaluators were experienced at rating SD and were familiar with the vocal tremor of ET. A Wilcoxon signed-rank test was used to study the pre- and posttreatment effect of DBS on voice. Unilateral left thalamic Vim stimulation (DBS on) significantly improved SD vocal dysfunction compared with no stimulation (DBS off), as measured by the USDRS (p < 0.01) and VRQOL (p < 0.01). In the experimental interrogation, both low-voltage Vim (p < 0.01) and multitarget Vim + Voa (p < 0.01) stimulation were significantly superior to low-voltage Voa stimulation. For the first time, the effects of high-frequency stimulation of different neural circuits in SD have been quantified. Unexpectedly, focused Voa (pallidal outflow) stimulation was inferior to Vim (cerebellar outflow) stimulation despite the classification of SD as a dystonia. While only a single case, scattered reports exist on the positive effects of thalamic DBS on dysphonia. A Phase 1 pilot trial (DEBUSSY; clinical trial no. NCT02558634, clinicaltrials.gov) is underway at the authors' center to evaluate the safety and preliminary efficacy of DBS in SD. The authors hope that this current report stimulates neurosurgeons to investigate this new indication for DBS.

Tic related local field potentials in the thalamus and the effect of deep brain stimulation in Tourette syndrome: Report of three cases

ObjectiveThree patients with intractable Tourette syndrome (TS) underwent thalamic deep brain stimulation (DBS). To investigate the role of thalamic electrical activity in tic generation, local field potentials (LFP), EEG and EMG simultaneously were recorded. MethodsEvent related potentials and event related spectral perturbations of EEG and LFP, event related cross-coherences between EEG/LFP and LFP/LFP were analyzed. As time locking events, the tic onsets were used. Spontaneous tics were compared to voluntary tic mimicking. The effect of tic suppression and DBS on thalamic LFPs was evaluated. ResultsAll three patients showed time-locked and prior to onset of spontaneous motor tics thalamic synchronization and thalamo-cortical cross-coherence. Also in three patients, not time-locked to motor tics, increased intra-thalamic coherences in the 1–8Hz frequency band were found. In one patient it was demonstrated that voluntary mimicked tics were preceded by premotor cortical and thalamic potentials. In this patient unilateral thalamic DBS contralaterally decreased the background thalamic activity. ConclusionsThe present study in three cases with TS shows that spontaneous tics in TS are preceded by repetitive coherent thalamo-cortical discharges, indicating that preceding a tic the basal ganglia circuits are “charged up”, ultimately leading to a motor tic. SignificanceThalamic LFP recording may lead to more insight in underlying pathophysiological mechanisms in TS.

Which Approach is Better: Bilateral Versus Unilateral Thalamic Deep Brain Stimulation in Patients with Fragile X–Associated Tremor Ataxia Syndrome

Fragile X-associated tremor ataxia syndrome (FXTAS) is a relatively recently described condition that is frequently misdiagnosed as essential tremor and then occasionally treated as such with deep brain stimulation (DBS) to the nucleus ventralis intermedius of the thalamus (Vim). Reports of ataxia worsening after bilateral Vim DBS in FXTAS patients are conflicting, and only five FXTAS patients treated with Vim DBS for intractable tremor have been reported in the literature, three of whom having undergone a bilateral procedure. We report a patient who underwent a staged Vim DBS procedure, with excellent contralateral hand tremor control and no worsening of ataxia after the first procedure, but immediate worsening of his ataxia after the second one, arguing in favor of a unilateral surgical approach for intractable tremor in FXTAS.

Unilateral thalamic deep brain stimulation in essential tremor demonstrates long-term ipsilateral effects

IntroductionDeep Brain Stimulation (DBS) of thalamus in essential tremor (ET) is effective for the treatment of contralateral tremors. Bilateral DBS controls tremors on both sides but is associated with increased morbidity and risks. We evaluated if unilateral surgery had ipsilateral benefits on tremors and thus could be a potentially safer alternative to bilateral DBS. MethodsMedication refractory ET patients undergoing unilateral thalamic DBS were included and longitudinally followed. Tremor rating scale was used to record total motor, arm tremor and activities of daily living (ADL) scores at baseline, six months and at last visit (three or more years after surgery). Postoperative scores were recorded with DBS turned OFF and ON. ResultsTwenty-two patients with a mean follow-up 3.4 ± 0.14 years were enrolled. When baseline scores were compared to scores with the DBS turned ON, significant improvements were noted in total tremor (40%), ADL (67%) and arm tremor scores both on the ipsilateral and the contralateral side at six months and at the last visit of follow-up (all p < 0.05). Ipsilateral arm tremor (∼56%) improvements were milder compared to the contralateral side (∼73%) tremors. ConclusionUnilateral thalamic DBS in ET demonstrates significant long-term benefits for ipsilateral arm tremors and can be offered to higher risk and to select patients.

Erratum: Long-term benefits in quality of life after unilateral thalamic deep brain stimulation for essential tremor

Erratum: Long-term benefits in quality of life after unilateral thalamic deep brain stimulation for essential tremor

Long-term benefits in quality of life after unilateral thalamic deep brain stimulation for essential tremor

The goal of this study was to evaluate short- and long-term benefits in quality of life (QOL) after unilateral deep brain stimulation (DBS) for essential tremor (ET). Patients who received unilateral DBS of the ventral intermediate nucleus of the thalamus between 1997 and 2010 and who had at least 1 follow-up evaluation at least 1 year after surgery were included. Their QOL was assessed with the Parkinson Disease Questionnaire-39 (PDQ-39), and ET was measured with the Fahn-Tolosa-Marin tremor rating scale (TRS) prior to surgery and then postoperatively with the stimulation in the on mode. Ninety-one patients (78 at 1 year; 42 at 2-7 years [mean 4 years]; and 22 at >7-12 years [mean 9 years]) were included in the analysis. The TRS total, targeted tremor, and activities of daily living (ADL) scores were significantly improved compared with presurgical scores up to 12 years. The PDQ-39 ADL, emotional well-being, stigma, and total scores were significantly improved up to 7 years after surgery compared with presurgical scores. At the longest follow-up, only the PDQ-39 stigma score was significantly improved, and the PDQ-39 mobility score was significantly worsened. Unilateral thalamic stimulation significantly reduces ET and improves ADL scores for up to 12 years after surgery, as measured by the TRS. The PDQ-39 total score and the domains of ADL, emotional well-being, and stigma were significantly improved up to 7 years. Although scores were improved compared with presurgery, other than stigma, these benefits did not remain significant at the longest (up to 12 years) follow-up, probably related in part to changes due to aging and comorbidities.

Primary writing tremor responds to unilateral thalamic deep brain stimulation

Primary writing tremor is a task associated tremor which occurs during and interferes with handwriting. Considered in most cases to be a nonprogressive disorder, a number of patients are significantly debilitated by the disease. The pathophysiology of the disorder is not fully understood, but felt to represent a variant of either essential tremor or dystonia versus a separate entity. Treatment has been limited to medications, writing devices and botulinum toxin type A for most patients. Recently, deep brain stimulation has been reported in a few patients as an effective option for those patients with medically refractory symptoms. We report our experience in a patient with primary writing tremor who underwent successful thalamic deep brain stimulation, discuss the current theories on the pathophysiology of the disorder and review the current literature of deep brain stimulation for refractory primary writing tremor.

NEUROSURGICAL TREATMENT OF TREMOR IN ANTI-MYELIN-ASSOCIATED GLYCOPROTEIN NEUROPATHY

Anti-myelin-associated glycoprotein (anti-MAG) neuropathy is an antibody-mediated demyelinating neuropathy, with monoclonal immunoglobulin M (IgM) antibodies. It is characterized by a progressive, symmetric, mainly sensory neuropathy and mild distal weakness.1,2 Gait disorder with ataxia is a prominent feature.2 Limb tremor is common, while head, chin, and voice tremor do not occur.2 We report a case of a patient with anti-MAG neuropathy and tremor who had a marked improvement in tremor and quality of life with unilateral thalamic deep brain stimulation (DBS). There have been few other case reports in the literature regarding neuropathic tremor and DBS.3 ### Case report. A right-handed 82-year-old woman with no family history of tremor presented with hand and feet paresthesia, followed by the development of hand tremor 12 months later. Diagnosis of anti-MAG neuropathy was made serologically. Neurophysiologic studies confirmed the presence of a demyelinating, sensorimotor neuropathy with prolongation of the distal motor latencies. The tremor was disabling and prevented feeding and dressing herself as well as performing personal hygiene activities. Corticosteroids, plasma exchange, and IV cyclophosphamide were tried for 12 months without benefit. Primidone and gabapentin also gave little effect. Propranolol was contraindicated due to asthma. Rituximab …

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.

Approche chirurgicale d’un tremblement de Holmes associé à un tremblement synchrone de haute fréquence

The effectiveness of thalamic stimulation is now clearly demonstrated for essential tremor, but remains to be demonstrated for other types of tremor. A young woman presented Holmes' tremor resulting from a pontine tegmental hemorrhage related to an arteriovenous malformation. A surgical approach was considered when major functional impairment persisted at 2-year follow-up despite drug therapy. The patient underwent unilateral thalamic deep brain stimulation (Vim); major improvement persisted at eighteen months follow-up. This observation is in line with previous reports suggesting that thalamic surgery can be one of the best options for treating medically intractable Holmes' tremor. The mechanism underlying the tremor, implying dentate-rubro-thalamic pathways is discussed. Moreover, the patient exhibited short periods of 16Hz tremor when her arms were maintained outstretched. Thalamic stimulation also appears to be effective for these high-frequency synchronous cerebellar bursts.

Neuropsychological and quality of life outcomes 12 months after unilateral thalamic stimulation for essential tremor

Objectives: To evaluate the one year cognitive, mood state, and quality of life (QoL) outcomes of unilateral thalamic deep brain stimulation (DBS) for essential tremor (ET). Methods: 40 patients diagnosed...

A prospective study of thalamic deep brain stimulation for the treatment of movement disorders in multiple sclerosis

The place for neurosurgical management of movement disorders in multiple sclerosis is unclear. To evaluate the potential benefits of unilateral thalamic deep brain stimulation (DBS) a prospective study was performed. Fifteen patients with confirmed MS and chronic, severe, drug-resistant movement disorders underwent stereotactic surgery to implant a thalamic DBS electrode using CT image guidance and intra-operative neurophysiological testing. The primary outcome measures were reduction in tremor severity and improvement in tests of hand function when the DBS electrode was turned on, 12 months after surgery. Secondary outcome measures included indices of disability, handicap, neuropsychological function and independence. Thirty-seven patients were assessed for treatment, but only 15 underwent surgery. In the 10 patients in whom implantation of the complete DBS system was carried out there was a significant reduction in the severity of tremor ( p = 0.02) and improvement in hand function ( p = 0.02). There were no benefits in any of the secondary outcome measures. Two patients had thalamocapsular haemorrhages at the site of electrode implantation and two had seizures in the follow-up period. Thalamic stimulation significantly reduced the tremor associated with MS and improved hand function in the targeted upper limb. However, there can be difficulties with identifying an optimal implantation site during operation, significant procedural morbidity and difficulty in predicting immediate outcome. It is also likely that the insignificant benefits of DBS on disability and handicap reflect persisting cerebeller dysmetria, and both the severity and diffuse nature of the disease process in this patient cohort.

Neuropsychological and Quality of Life Changes Following Unilateral Thalamic Deep Brain Stimulation in Parkinson's Disease: A One-Year Follow-up

The long-term neuropsychological and quality of life (QOL) outcomes of unilateral thalamic deep brain stimulation (DBS) in patients with intractable Parkinson's disease (PD) have not heretofore been described. Six patients diagnosed with PD underwent unilateral DBS implantation into a verified thalamic VIM nucleus target. Participants completed presurgical neuropsychological evaluation and follow-up assessment at approximately one year postsurgery. Compared to their presurgical scores, PD patients exhibited significant improvement on measures of conceptualization, verbal memory, emotional adjustment, and QOL at one-year follow-up. A few nominal declines were observed across the battery of tests. These data provide preliminary support for the long-term neurocognitive safety and QOL improvements following thalamic stimulation in patients with PD.

Neuropsychological and quality of life outcome after thalamic stimulation for essential tremor.

To evaluate short-term effects of unilateral thalamic deep brain stimulation (DBS) on cognition, mood state, and quality of life in patients with essential tremor (ET). Unilateral thalamotomy and thalamic DBS are effective in alleviating refractory tremor contralateral to the side of surgery. Thalamotomy can lead to cognitive morbidity, and DBS might be a preferable surgical intervention given potential avoidance or reversibility of such morbidity. Although unilateral thalamic DBS is cognitively safe and leads to quality of life improvement in PD, its neurobehavioral effects in ET are unknown. Forty patients with ET were administered a broad neuropsychological test battery, measures of mood state, and generic and disease-specific quality of life measures approximately 1 month before and 3 months after surgery (left hemisphere, 38 patients). Unilateral thalamic DBS was associated with significant improvements in tremor and dominant-hand fine visuomotor coordination. Statistically significant but clinically modest gains were observed on tasks of visuoperceptual and constructional ability, visual attention, delayed word list recognition, and prose recall. Only lexical verbal fluency declined significantly after surgery. Patients rated themselves as less anxious after surgery, and they perceived their quality of life as improved significantly. In particular, patients reported improved quality of life with respect to activities of daily living, stigma, emotional well-being, and communication. Unilateral thalamic DBS for ET is cognitively safe and associated with improvements in anxiety and quality of life in the near term and in the absence of operative complications. Patients were better able to carry out activities of daily living after surgery, and they reported improvement in several psychosocial domains of quality of life.