Thalamic Ventralis Intermedius Nucleus Research Articles

Response to Thalamic Ventralis Intermedius Nucleus Deep Brain Stimulation in Essential Tremor vs. Essential Tremor-Plus.

Introduction: Essential tremor (ET) is a tremor syndrome characterized by bilateral, upper limb action tremor. Essential tremor-plus (ET-plus) describes ET patients with additional neurologic signs. It is unknown whether there is a difference in response to treatment with ventralis intermedius nucleus deep brain stimulation (VIM DBS) in patients with ET and ET-plus. Due to potential variability in underlying etiology in ET-plus, there is a concern that ET-plus patients may have worse outcomes. The aim of this study was to identify whether patients with ET-plus have worse tremor outcomes after VIM DBS than patients with ET.Methods: This is a retrospective chart and video review evaluating VIM DBS outcomes by comparing changes from baseline in the Fahn-Tolosa-Marin Tremor Rating Scale Part B (FTM-B) for the treated limb between patients with ET and ET-plus at follow-up examinations. Patients were re-classified as having ET or ET-plus using pre-operative examination videos by two independent movement disorders neurologists blinded to patient characteristics. As a secondary outcome, we evaluated for correlations and potential predictors of treatment response.Results: Twenty-six patients were included: 13 with ET, 13 with ET-plus. There were no significant differences in the change in FTM-B scores between the ET and ET-plus patients at each follow-up examination. None of the included patients developed new symptoms compatible with dystonia, parkinsonism or gait disturbances.Conclusions: Patients with ET-plus had tremor improvement from VIM DBS, with no differences when compared to those with ET, without emergence of postoperative neurological issues. Patients with ET-plus should still be considered good candidates for VIM DBS for treatment of tremor.

Cognitive safety after unilateral magnetic resonance-guided focused ultrasound thalamotomy for essential tremor

Essential tremor (ET) is the most common movement disorder, affecting 1% of the population worldwide. There is sound evidence that medically refractory tremor improves with thalamotomy and deep brain stimulation...

Long-term Thalamic Deep Brain Stimulation for Essential Tremor: Clinical Outcome and Stimulation Parameters.

The reasons underlying the loss of efficacy of deep brain stimulation (DBS) of the thalamic nucleus ventralis intermedius (VIM-DBS) over time in patients with essential tremor are not well understood. Long-term clinical outcome and stimulation parameters were evaluated in 14 patients with essential tremor who underwent VIM-DBS. The mean ± standard deviation postoperative follow-up was 7.7 ± 3.8 years. At each visit (every 3-6 months), tremor was assessed using the Fahn-Tolosa-Marin tremor rating scale (FTM-TRS) and stimulation parameters were recorded (contacts, voltage, frequency, pulse width, and total electrical energy delivered by the internal generator [TEED 1sec]). The mean reduction in FTM-TRS score was 73.4% at 6 months after VIM-DBS surgery (P < 0.001) and 50.1% at the last visit (P < 0.001). The gradual worsening of FTM-TRS scores over time fit a linear regression model (coefficient of determination [R2] = 0.887; P < 0.001). Stimulation adjustments to optimize tremor control required a statistically significant increase in voltage (P = 0.01), pulse width (P = 0.01), frequency (P = 0.02), and TEED 1sec (P = 0.008). TEED 1sec fit a third-order polynomial curve model throughout the follow-up period (R2 = 0.966; P < 0.001). The initial exponential increase (first 4 years of VIM-DBS) was followed by a plateau and a further increase from the seventh year onward. The current findings suggest that the waning effect of VIM-DBS over time in patients with essential tremor may be the consequence of a combination of factors. Superimposed on the progression of the disease, tolerance can occur during the early years of stimulation.

Prelemniscal Radiations: A New Reliable Landmark of the Thalamic Nucleus Ventralis Intermedius Location?

Background: The thalamic nucleus ventralis intermedius (Vim nucleus) is the main surgical target for the management of intractable tremor. The Vim nucleus cannot be reliably located with routine stereotactic imaging, and so targeting relies on indirect coordinates. Objective: We propose to investigate if colored fractional anisotropy (FA) mapping can help to locate the Vim nucleus by identifying its borders, particularly the prelemniscal radiations (Raprl) that lie below and behind the nucleus. Method: We retrospectively reviewed the colored FA maps for 18 consecutive patients having undergone gamma knife stereotactic Vim thalamotomy for disabling tremor. Results: The Raprl were easily located on colored FA maps and enabled the identification of the lower and posterior borders of the Vim nucleus in all patients. In the medial plane, the mean distance ± SD between the Raprl and Vim nucleus was 0.77 ± 1.19 mm (range: 0.1-3.3). The Raprl were located 1.35 ± 1.33 mm (range: 0.2-3.9) behind the Vim nucleus and 1.99 ± 1.23 mm (range: 0.7-4.4) below it. The mean vector distance ± SD between the Vim nucleus and the Raprl was 3 ± 1.38 mm (range: 1.25-5.2). Conclusion: The Raprl can be easily seen on colored FA maps and constitute a reliable landmark for the borders of the Vim nucleus.

The variability of atlas-based targets in relation to surrounding major fibre tracts in thalamic deep brain stimulation.

In essential tremor (ET), the main target for deep brain stimulation (DBS) is the thalamic ventralis intermedius nucleus (Vim). This target cannot be identified on conventional magnetic resonance imaging (MRI). Therefore, targeting depends on probabilistic coordinates derived from stereotactic atlases. The goal of our study was to investigate the variability of atlas-based Vim targets in relation to surrounding major fibre tracts. With the MRI and computed tomography (CT) scan data of ten patients who underwent DBS, we planned atlas based Vim targets in both hemispheres. We also performed deterministic fibre-tracking with diffusion tensor imaging (DTI) of the dentato-rubro-thalamic tract (DRTT), pyramidal tract (PT) and lemniscus medialis (LM) in all 20 hemispheres. Subsequently, we measured the distance from the atlas-based Vim target to each tract along the medial/lateral (x-coordinate), anterior/posterior (y-coordinate) and superior/inferior axis (z-coordinate). Seventeen out of 20 DRTTs could be depicted with our standardised DTI/fibre-tracking parameters. The PT and the LM could be displayed in all 20 hemispheres. The atlas-based Vim target was found inside the DRTT in 11 (concerning the x-coordinate) and 10 hemispheres (concerning the z-coordinate). Regarding the anterior/posterior direction, the target was posterior to the DRTT in 11 cases. In 19 hemispheres the Vim target was located medial and superior to the PT and in 17 hemispheres posterior to it. Concerning the LM, the Vim target was found inside the LM in 16 (regarding the x-coordinate) and in 14 cases (regarding the z-coordinate). In eight cases it was located inside and in 12 cases anterior to the LM concerning the y-coordinate. We found a considerable variability of the location of atlas-based target points of the ventralis intermedius nucleus in relation to neighbouring major fibre tracts in individual patients. These results suggest that individualised targeting to structures not directly visible on conventional MRI is necessary.

Mechanisms of deep brain stimulation for essential tremor

Although essential tremor is often thought of as benign, it can be disabling to the point of justifying invasive deep brain stimulation (DBS). However, the mechanisms by which thalamic and subthalamic stimulation suppress tremor are poorly understood. In this issue of Brain , Groppa et al. (2014) quantified the performance of seven patients with essential tremor in a reaching task to determine the DBS target structures associated with therapeutic reduction in tremor and with the side effect of stimulation-induced ataxia. The optimum site of stimulation was usually in the posterior subthalamic area, beneath the inferior border of the thalamic nucleus ventralis intermedius. Probabilistic diffusion tractography identified the dentatothalamic tract as the key therapeutic DBS target structure. Supratherapeutic stimulation of this site produced upper limb ataxia, despite continued suppression of tremor. The authors systematically varied stimulation pulse strength and duration to find that stimulation chronaxies of 27 and 52 µs were associated with tremor suppression and the induction of ataxia, respectively. Chronaxie is loosely defined as the minimum duration at which a current twice threshold (minimum current with indefinitely long pulse duration) elicits a response and provides a clue as to the properties of the axons recruited. They reasoned that two different populations of large myelinated nerve fibres were affected: (i) dentatothalamic axons for the therapeutic effect; and (ii) afferent or efferent axons of the red nucleus for the stimulation-induced ataxia. However, the involvement of rubral pathways could not be confirmed with diffusion tractography. This work is an important contribution to a growing literature addressing the mechanisms of DBS and the preferred site of DBS stimulation for essential tremor. Ventralis intermedius has historically been the preferred stereotactic target for thalamotomy and DBS in the treatment of essential tremor and other tremor disorders (Miocinovic et al. , 2013), but recent postoperative correlations …

Targeting accuracy of transcranial magnetic resonance–guided high-intensity focused ultrasound brain therapy: a fresh cadaver model

This work aimed at evaluating the accuracy of MR-guided high-intensity focused ultrasound (MRgHIFU) brain therapy in human cadaver heads. Eighteen heads of fresh human cadavers were removed with a dedicated protocol preventing intracerebral air penetration. The MR images allowed determination of the ultrasonic target: a part of the thalamic nucleus ventralis intermedius implicated in essential tremor. Osseous aberrations were corrected with simulation-based time reversal by using CT data from the heads. The ultrasonic session was performed with a 512-element phased-array transducer system operating at 1 MHz under stereotactic conditions with thermometric real-time MR monitoring performed using a 1.5-T imager. Dissection, imaging, targeting, and planning have validated the feasibility of this human cadaver model. The average temperature elevation measured by proton resonance frequency shift was 7.9°C ± 3°C. Based on MRI data, the accuracy of MRgHIFU is 0.4 ± 1 mm along the right/left axis, 0.7 ± 1.2 mm along the dorsal/ventral axis, and 0.5 ± 2.4 mm in the rostral/caudal axis. Despite its limits (temperature, vascularization), the human cadaver model is effective for studying the accuracy of MRgHIFU brain therapy. With the 1-MHz system investigated here, there is millimetric accuracy.

Unilateral Thalamic Deep Brain Stimulation for Disabling Kinetic Tremor in Multiple Sclerosis

Surgical options of multiple sclerosis (MS) tremor treatment are limited and narrowed to thalamotomy or deep brain stimulation of the thalamic nucleus ventralis intermedius. Lack of qualification protocol frequently results in poor outcome. To determine prospectively the efficacy and safety of unilateral ventralis intermedius deep brain stimulation as a tool to control disabling kinetic arm tremor related to MS. Neurological and neuropsychological evaluations were performed 1 month and 1 day before surgery and 1, 3, and 6 months after surgery. The evaluation included measurement of tremor and dexterity, Extended Disability Status Scale, Mini Mental State Examination, and quality-of-life assessment. Nine consecutive patients were enrolled in the group. Mean age at the time of surgery was 38.9 ± 9 years; median Extended Disability Status Scale at baseline was 7.1. Mean MS duration was 11.7 years, and mean tremor duration was 6.11 years. Mean postural and kinetic scores and hand capacity were measured. One month after surgery, median scores off and on stimulation were 12 and 6 for postural tremor, 12 and 10.5 for kinetic tremor score, 12 and 7.5 for manual capacity, and 22 and 20 for functional handicap, respectively. Similar results were 10 and 4, respectively, at the 3-month follow-up. Six months after surgery, median scores off and on stimulation were 10.4 and 4 for postural tremor and 12 and 7.8 for kinetic tremor, respectively. This prospective study confirms the value and safety of ventralis intermedius deep brain stimulation for treatment of kinetic tremor related to MS. Accurate and precise presurgical qualification plays a key role in successful treatment.

Parkinsonian thalamic electrical activities reveal voluntary versus involuntary movements in conflict

Objective: The aim of this study was to analyze the correlation between neuronal responses in the thalamic ventralis intermedius (Vim) nucleus to peripheral, natural stimulation and the modulation of tremor by electrical stimulation during stereotactic thalamotomy.Design and methods: The authors studied 36 patients with hand tremor using a microelectrode. The responses of tremor to electrical stimulation were analysed electromyographically. Sixty stimulation sites were divided into three groups.Results: Group A (20 sites) where responses to stretching of the contralateral forearm muscles were recorded. Group B (26 sites) where responses to stretching of the other muscles of the upper extremity were recorded. Electrical stimulation at sites in groups A and B temporarily suppressed the contralateral tremor, but the minimum current intensity to suppress tremor at sites in group A was less than that in group B. Electrical stimulation in group C (14 sites), where kinesthetic responses of contralateral lower extremity were recorded, resulted in increased amplitude of hand tremor. Selective coagulation including the area of tremor suppression resulted in abolition of the tremor in all patients.Conclusions: These results suggest that the most effective site for thalamotomy may also be suitable for chronic stimulation in the Vim nucleus.

Deep brain stimulation for treatment of hemichorea-hemiballism after craniopharyngioma resection: long-term follow-up

Hemichorea-hemiballism is a rare movement disorder that has various causes. In treatment-resistant cases, both thalamic and pallidal functional procedures have been shown to yield beneficial results. Until now it has not been clarified whether the thalamus or the pallidum would yield a superior outcome. After resection of a craniopharyngioma in this patient at the age of 49 years, hemichorea-hemiballism developed, with a latency of several weeks. Because the patient was greatly impaired by the movement disorder, she underwent implantation of deep brain stimulation (DBS) electrodes in the thalamic ventralis intermedius nucleus and the posteroventral lateral globus pallidus internus. Although both pallidal and thalamic stimulation could suppress the movement disorder, the voltage needed was clearly less with thalamic than with pallidal stimulation. At the last available follow-up 25 months postoperatively, complete subsidence of hemichorea-hemiballism was achieved with long-term thalamic stimulation. Long-term DBS therapy is an efficient treatment modality for refractory hemichorea-hemiballism in the long run (> 2 years). A bifocal (thalamic and pallidal) target paradigm allowed selection of the optimal stimulation site. Thalamic DBS was more favorable with regard to energy consumption.

Deep Brain Stimulation in Benign Tremulous Parkinsonism

Benign tremulous parkinsonism (BTP) is characterized by prominent resting plus action tremor, mild parkinsonism with limited disability or progression apart from tremor, and a less-robust response to levodopa therapy. This disorder has an uncertain pathophysiologic relationship to idiopathic Parkinson disease. Deep brain stimulation (DBS) should be efficacious for this condition, but there is no previously published experience. To assess the clinical outcomes and surgical complications of patients with BTP who underwent DBS. Retrospective case series. Tertiary care medical center. Twelve men and 3 women with BTP who underwent DBS for levodopa-refractory tremor. Tremor status after DBS, preoperative vs postoperative scores on the Fahn-Tolosa-Marin tremor scale, and the presence of adverse events. Of the 15 patients, 8 underwent unilateral thalamic nucleus ventralis intermedius (VIM), 4 bilateral VIM, and 3 bilateral subthalamic nucleus DBS. At last follow-up at a median of 4 years post-DBS, 7 patients were tremor free, 6 had only trace tremor, and 2 were definitely improved but with residual tremor. The median preoperative Fahn-Tolosa-Marin tremor scale score was 17 (range, 11-21); the tremor scale score at the last videotaped follow-up was 1 (range, 0-6). Median time between the 2 videotapes was 11.5 months (range, 3-14 months). No patients experienced adverse events after the surgical procedure. These findings support the efficacy of DBS, with VIM and STN targets, in medically refractory BTP-related tremor. Further studies are needed to explore the long-term durability of response and to better compare the surgical targets.

Body weight gain and deep brain stimulation

Deep brain stimulation (DBS) is a neurosurgical technique that has now been available for some 25years. It is used in the treatment of various motor disorders, e.g. Parkinson's disease (PD), essential tremor and dystonia, and neuropsychiatric illnesses, e.g. obsessive–compulsive disorder and Tourette syndrome. The surgical targets of DBS include the thalamic ventralis intermedius nucleus (Vim), the globus pallidus internus (GPi) and more recently the subthalamic nucleus (STN), currently considered as the reference target in the treatment of PD. In the last ten years, most studies in PD patients have described a rapid and marked weight gain in the months following DBS of the STN. This weight gain sometimes induces obesity and can have metabolic repercussions. The physiopathological mechanisms responsible for the weight gain are multifactorial (changes in energy metabolism and eating behaviour, reduction of motor complications, etc.).This review reports current knowledge concerning weight changes in patients treated by DBS with different surgical targets. It also describes the mechanisms responsible for weight gain and the health outcome for the patients.

Thalamic deep brain stimulation for tremor among multiple sclerosis patients

Background and purposeDisabling tremor might be the main cause of disability of multiple sclerosis (MS) patients. Neuromodulation with deep brain stimulation of the thalamic nucleus ventralis intermedius (Vim DBS) is a well accepted method of neurosurgical treatment of tremor related to essential tremor or Parkinson disease. Vim DBS is not widely used to control MS tremor. Material and methodsFive MS patients with tremor (3 females and 2 males) were treated with Vim DBS. Age at implantation was 37 ± 5 years. MS lasted from 5 to 12 years (mean 6) and tremor was the main cause of disability of those patients from 2 to 5 years (mean 3) before surgery. Clinical condition of the group was evaluated with spirography, the modified Fahn scale and the modified Activity of Daily Living (ADL) scale. Evaluations were performed before surgery and 3 months after surgery. MRI exclusion criteria were the presence of a thalamic hyperintense signal in T2-weighted images or ventricular enlargement. The procedures of implantation were performed under local and general anaesthesia. ResultsIntensity of contralateral limb tremor during intraoperative macrostimulation was reduced in the whole group. The therapeutic effect of DBS was maintained at three-month follow-up. Mean contralateral limb tremor reduction was 40%. Mean ADL score improved by 18%. No mortality or morbidity was reported in the group. ConclusionsThe study confirms the value and safety of Vim DBS for treatment of MS-related tremor. Further study on a larger population and introduction of a qualification protocol might increase efficacy of the treatment.

Long-term electrical inhibition of deep brain targets in movement disorders.

Stimulation of the thalamic nucleus ventralis intermedius (Vim) at high (130-Hz) frequency has been used over the last 8 years as a treatment in 134 patients with movement disorders (91 Parkinson's disease [PD], 23 essential tremor [ET], 21 various dyskinesias and dystonias, including four multiple sclerosis [MS]), implanted with long-term electrodes connected to a programmable stimulator. In PD patients, tremor was selectively suppressed for < or = 11 years. In ET patients, results were satisfactory, but in 35% of the cases deteriorated with time, when tremor had an action component. Other types of dyskinesias were much less influenced. Sixty-eight patients were bilaterally implanted, and 14 were implanted contralateral to a previous thalamotomy. Side effects were often minor, well tolerated, and immediately reversible. Three secondary scalp infections led to temporary removal of implanted material. There was no permanent morbidity. Long-term Vim stimulation, which is reversible, adaptable, and well tolerated, even by bilaterally operated-on (68 of 134) and by elderly patients, should replace thalamotomy in the regular surgical treatment of parkinsonian and essential tremors. More recently, we stimulated the subthalamic nucleus (STN) in 51 patients (44 bilateral) and the globus pallidus internus (GPi) in 12 patients (seven bilateral). STN stimulation has a spectacular effect on akinesia and rigidity and may improve the patients so as to maintain them all day at a level similar to their best "on" periods. A 30-50% reduction in drug dosage was possible in most of the patients. GPi stimulation has indications and effects similar to those of pallidectomy: abnormal involuntary movements are totally suppressed, whereas effects on akinesia and rigidity are not so important as they are with STN stimulation. For all three targets, morbidity is low and reversible, even when bilateral implantations are performed. The deep-brain stimulation method has now proved its safety as compared with ablative surgery and is able to provide a significant improvement to these severely disabled patients. Long-term follow up is establishing the security of the method, which should be considered in earlier stages of the disease actively to participate to rehabilitation.

Quantification of Temporal and Spatial Accuracy of Alternating Arm Movements in Multiple Sclerosis Patients Treated with Deep Brain Stimulation of the Thalamic Ventralis Intermedius Nucleus (VIM)

In patients with multiple sclerosis (MS) ataxia is a common symptom, which is barely influenced by pharmacological treatment. We studied whether stimulation of the thalamic ventralis intermedius nucleus (VIM) improves the performance of alternating forearm movements in MS patients. We investigated 6 patients with primary (n=1) or secondary (n=5) chronic progressive MS (age 36-66 years, median 41.5 years, median EDSS [expanded disability status scale] 6.5). Patients were seated in a chair with one arm abduced at right angles to the body. This arm was strapped into a splint with one fixed section for the upper arm and one movable section for the forearm. The latter allowed horizontal movements in the elbow joint. The patients had to perform rhythmic alternating flexion and extension movements in the elbow joint. The rhythm and spatial extent of movements were indicated acoustically by a click tone stimulator and by marks respectively. Six manoeuvres (spatial extents of 48 degrees , 83 degrees at frequencies of 0.9 Hz, 1.5 Hz, and 2.5 Hz each) had to be performed. A potentiometer converted the horizontal movements of the forearm into a variable voltage. Forearm movements were measured with and without contralateral VIM stimulation. In all patients, spatial accuracy of the alternating forearm movements improved significantly after the stimulation had been switched on. Temporal accuracy increased during VIM stimulation in 5 of 6 patients. In 1 of 6 patients the spatial but not the temporal movement accuracy improved during stimulation. During VIM stimulation, performance of alternating forearm movements improved significantly. This might indicate that VIM stimulation could be a therapeutic alternative in the treatment of upper limb ataxia in MS.

Long-term deep brain stimulation in elderly patients with cardiac pacemakers

Deep brain stimulation (DBS) has become an accepted therapy for movement disorders such as Parkinson disease (PD) and essential tremor (ET), when these conditions are refractory to medical treatment. The presence of a cardiac pacemaker is still considered a contraindication for DBS in functional neurosurgery. The goal of this study was to evaluate the technical and clinical management of DBS for the treatment of movement disorders in elderly patients with cardiac pacemakers. Six patients with cardiac pacemakers underwent clinical and cardiac examinations to analyze the safety of DBS in the treatment of movement disorders. Four patients suffered from advanced PD and two patients had ET. The mean age of these patients at surgery was 69.5 years (range 63-79 years). The settings of the pacemakers were programmed in a manner considered to minimize the chance of interference between the two systems. There were no adverse events during surgery. Four patients underwent stimulation of the thalamic ventralis intermedius nucleus (VIM), and two patients stimulation of the subthalamic nucleus. In general, bipolar sensing was chosen for the cardiac pacemakers. In all but one patient the quadripolar DBS electrodes were programmed for bipolar stimulation. Several control electrocardiography studies, including 24-hour monitoring, did not show any interference between the two systems. At the time this paper was written the patients had been followed up for a mean of 25.3 months (range 4-48 months). In certain conditions it is safe for patients with cardiac pacemakers to receive DBS for treatment of concomitant movement disorders. Cardiac pacemakers should not be viewed as a general contraindication for DBS in patients with movement disorders.

Gamma knife thalamotomy for movement disorders: evaluation of the thalamic lesion and clinical results

The authors studied the effects of gamma knife thalamotomy (GKT) on Parkinson disease-related tremor and essential tremor before and after reloading of radioactive cobalt. Based on experience in stereotactic thalamotomy aided by depth microrecording, the target was located at the lateral border of the thalamic ventralis intermedius nucleus (VIM). For more precise targeting, the percentage representation of the thalamic VIM in relation to the entire thalamic length is useful. The location of the target was determined on magnetic resonance (MR) imaging and computerized tomography scanning. A maximum dose of 130 Gy was delivered to the target by using a single isocenter with the 4-mm collimator. In more recent cases, a systematic follow-up examination was performed at 3, 6, 12, 18, and 24 months after GKT. Since 1993, the authors have treated 70 patients with PD. Throughout the series the same dosimetric technique has been used. The course after GKT was compared between the 25 cases with PD treated before reloading and the 35 cases treated after reloading. In the majority (80-85%) treated after reloading, tremor and rigidity were reduced around 6 months after GKT. In the cases treated before reloading this effect took approximately 1 year. The thalamic reaction on MR imaging showed the same two lesion types in both series: a restricted and a diffuse. After reloading the restricted lesion was more frequent and the lesion volume was smaller. The shorter delay in clinical improvement and smaller lesion size may be related to an increased radiation dose.

Gamma knife thalamotomy for movement disorders: evaluation of the thalamic lesion and clinical results

Object. The authors studied the effects of gamma knife thalamotomy (GKT) on Parkinson disease-related tremor and essential tremor before and after reloading of radioactive cobalt. Methods. Based on experience in stereotactic thalamotomy aided by depth microrecording, the target was located at the lateral border of the thalamic ventralis intermedius nucleus (VIM). For more precise targeting, the percentage representation of the thalamic VIM in relation to the entire thalamic length is useful. The location of the target was determined on magnetic resonance (MR) imaging and computerized tomography scanning. A maximum dose of 130 Gy was delivered to the target by using a single isocenter with the 4-mm collimator. In more recent cases, a systematic follow-up examination was performed at 3, 6, 12, 18, and 24 months after GKT. Since 1993, the authors have treated 70 patients with PD. Throughout the series the same dosimetric technique has been used. The course after GKT was compared between the 25 cases with PD treated before reloading and the 35 cases treated after reloading. In the majority (80–85%) treated after reloading, tremor and rigidity were reduced around 6 months after GKT. In the cases treated before reloading this effect took approximately 1 year. The thalamic reaction on MR imaging showed the same two lesion types in both series: a restricted and a diffuse. After reloading the restricted lesion was more frequent and the lesion volume was smaller. Conclusions. The shorter delay in clinical improvement and smaller lesion size may be related to an increased radiation dose.

Model Based Development of Novel Deep Brain Stimulation Techniques

Pathological synchronization is a hallmark of several neurological diseases like Parkinson's disease (PD) or essential tremor [Alberts et al., Nature 1969; 221: 670; Nini et al., J Neurophys 1995; 74: 1800]. For example, a pacemaker-like population of neurons, which fires in a synchronized and periodical manner, provokes the Parkinsonian resting tremor [Alberts et al., Nature 1969; 221: 670]. In contrast, an uncorrelated, i.e., desynchronized firing pattern of these neuronal populations is characteristic in healthy subjects [Nini et al., J Neurophys 1995; 74: 1800]. In medically intractable patients, electrical deep brain stimulation (DBS) is administered via depth electrodes chronically implanted in the subthalamic nucleus of the thalamic ventralis intermedius nucleus [Benabid et al., Lancet 1991; 337: 403]. For that purpose, a permanent high-frequency (>100Hz) periodic pulse train stimulation is used. Up to now the mechanism of high-frequency DBS is not yet sufficiently understood [Benabid et al., Lancet 1991; 337: 403]. We initiated a model-based development of novel stimulation protocols to find milder and more effective DBS techniques [Tass, Phase Resetting in Medicine and Biology, Springer, 1999; Tass, Biol Cyb 2003; 89: 81]. In a first clinical study performed during electrode implantation, we have shown that the coordinated reset via multiple/several sites can suppress the peripheral tremor, even if the standard high-frequency DBS has no tremor suppressive effect at all [Tass et al., submitted (2004)]. Here we present a technique for the desynchronization of a strongly synchronized target population which we expect to be even more effective and milder. For this, delayed mean field potentials are administered at different sites within a neuronal population to establish a desynchronized state. According to detailed theoretical investigations and simulations, we expect the novel desynchronization technique to be considerably milder, to act in a demand-controlled way and to be simple in realization. We use a microscopic model of a neuronal population in a relevant target area to show that the method is robust and does not require time consuming calibration. It is suggested that the novel technique is used for deep brain stimulation in patients suffering from Parkinson's disease, essential tremor or epilepsy.

Deep brain stimulation for the treatment of parkinsonian, essential, and poststroke tremor: a suitable stimulation method and changes in effective stimulation intensity.

The tremor-suppression effect resulting from long-term stimulation of the thalamic nucleus ventralis intermedius (Vim) and the nucleus ventralis oralis posterior (Vop) was examined in the treatment of parkinsonian, essential, and poststroke tremor. After identifying the accurate anterior border of the nucleus ventrocaudalis (Vc), deep brain stimulation (DBS) electrodes with four contacts were inserted into the Vim-Vop region at an angle of between 40 and 50 degrees from the horizontal plane of the anterior commissure-posterior commissure line. Two distal contacts were placed on the Vim side and two proximal contacts on the Vop side. The best sites of stimulation and parameters of bipolar stimulation were selected in each case and follow-up examinations were conducted for at least 2 years. In all 15 cases of parkinsonian tremor (18 sides) and in 14 of 15 cases of essential tremor (24 of 25 sides), cathodal stimulation of the Vim side with anodal stimulation of the Vop side was determined to be the best choice to suppress the tremor. In poststroke tremor, however, six of 12 cases (six of 12 sides) were selected for cathodal stimulation of the Vop side with anodal stimulation of the Vim side. The average stimulation intensity 1 month after initiation of DBS was 1.61 V in cases of parkinsonian tremor, 1.99 V in cases of essential tremor, and 2.39 V in cases of poststroke tremor. A comparison of stimulation intensities required at 1 and 24 months after initiation of DBS revealed that the lowest effective stimulation intensity increased 24.2% in cases of parkinsonian tremor, 21% in cases of poststroke tremor, and 46.9% in cases of essential tremor. Suppression of tremor was achieved in all cases (42 cases, 55 sides) during a period of 2 years. Nevertheless, two cases of poststroke tremor required dual-lead stimulation at the unilateral Vim-Vop region from the start of DBS, and two cases of essential tremor and one case of poststroke tremor required a stimulation intensity that was high enough to evoke unpleasant paresthesia and slight motor contraction during the follow-up period. Effective stimulation sites and stimulation intensities differ in different kinds of tremor; Vim and Vop stimulation is necessary in many cases. Interactions of the Vim and Vop under the control of interconnected areas of the motor circuitry may play an important role in both the development and DBS-induced suppression of tremor.