Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as a treatment of movement disorders

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✓ Tremor was suppressed by test stimulation of the thalamic ventralis intermedius (VIM) nucleus at high frequency (130 Hz) during stereotaxy in nonanesthetized patients suffering from Parkinson's disease or essential tremor. Ventralis intermedius stimulation has since been used by the authors over the last 8 years as a treatment in 117 patients with movement disorders (80 cases of Parkinson's disease, 20 cases of essential tremor, and 17 cases of various dyskinesias and dystonias including four multiple sclerosis). Chronic electrodes were stereotactically implanted in the VIM and connected to a programmable stimulator. Results depend on the indication. In Parkinson's disease patients, tremor, but not bradykinesia and rigidity, was selectively suppressed for as long as 8 years. Administration ofl-Dopa was decreased by more than 30% in 40 Parkinson's disease patients. In essential tremor patients, results were satisfactory but deteriorated with time in 18.5% of cases, mainly for patients who presented an action component of their tremor. In other types of dyskinesias (except multiple sclerosis), results were much less favorable. Fifty-nine patients underwent bilateral implantation and 14 other patients received implantation contralateral to a previous thalamotomy. Thirty-seven patients (31.6%) experienced minor side effects, which were always well tolerated and immediately reversible. Three secondary scalp infections led to temporary removal of the implanted material. There was no permanent morbidity. This tremor suppression effect could be due to the inhibition or jamming of a retroactive loop. Chronic VIM stimulation, which is reversible, adaptable, and well tolerated even by patients undergoing bilateral surgery (74 of 117 patients) and by elderly patients, should replace thalamotomy in the regular surgical treatment of parkinsonian and essential tremors.

Abstract

✓ Tremor was suppressed by test stimulation of the thalamic ventralis intermedius (VIM) nucleus at high frequency (130 Hz) during stereotaxy in nonanesthetized patients suffering from Parkinson's disease or essential tremor. Ventralis intermedius stimulation has since been used by the authors over the last 8 years as a treatment in 117 patients with movement disorders (80 cases of Parkinson's disease, 20 cases of essential tremor, and 17 cases of various dyskinesias and dystonias including four multiple sclerosis). Chronic electrodes were stereotactically implanted in the VIM and connected to a programmable stimulator. Results depend on the indication. In Parkinson's disease patients, tremor, but not bradykinesia and rigidity, was selectively suppressed for as long as 8 years. Administration ofl-Dopa was decreased by more than 30% in 40 Parkinson's disease patients. In essential tremor patients, results were satisfactory but deteriorated with time in 18.5% of cases, mainly for patients who presented an action component of their tremor. In other types of dyskinesias (except multiple sclerosis), results were much less favorable. Fifty-nine patients underwent bilateral implantation and 14 other patients received implantation contralateral to a previous thalamotomy. Thirty-seven patients (31.6%) experienced minor side effects, which were always well tolerated and immediately reversible. Three secondary scalp infections led to temporary removal of the implanted material. There was no permanent morbidity. This tremor suppression effect could be due to the inhibition or jamming of a retroactive loop. Chronic VIM stimulation, which is reversible, adaptable, and well tolerated even by patients undergoing bilateral surgery (74 of 117 patients) and by elderly patients, should replace thalamotomy in the regular surgical treatment of parkinsonian and essential tremors.

The modern surgical treatment of tremor was introduced 30 years ago when an unexpected intraoperative complication, which occurred during pyramidotomy,59 led Cooper and colleagues22–24 to the discovery that destruction of portions of the thalamus suppressed tremor in a patient with Parkinson's disease. The accidental lesion of the anterior choroid artery induced an infarction of the anterior and lateral parts of the thalamus, and at the end of the surgical procedure, the patient was permanently relieved of her tremor, although the pyramidotomy had not been performed. According to the previous work of Hassler,37 this accidental observation was exploited and extensive work was done to determine the best functional target. Although multiple lesions were advocated to relieve both bradykinesia and tremor, which led to performing pallidotomy for bradykinesia and thalamotomy for tremor during the same procedure, it appeared quite rapidly that the most effective target was in the thalamus and that the most sensitive symptom was tremor. Over the years, this target was progressively restricted to the posterior part of the motor area of the lateral thalamus and finally to the ventralis intermedius (VIM) nucleus, where smaller lesions were achieved.4,36,38–40,42,51,62,68,69,71,77,89,90,93,94 Although a spectacular and total suppression of tremor could be obtained in a high percentage of patients undergoing surgery, recurrences were nonetheless observed in approximately 4% to 20%42 of these patients after several weeks or years. When the lesion size was increased to prevent this recurrence, morbidity such as motor deficit, dystonia, speech disturbance, and sensory loss were observed with a reported frequency of approximately 25% transitory deficits and 2% to 9% permanent deficits.87,89 In addition, bilateral procedures, although reported to be feasible,57 were often associated with severe neuropsychological deficits56 and were thus rarely performed as a routine procedure.

The advent of l-Dopa27 therapy totally changed the therapeutic landscape of the disease, and for decades the surgical treatment of Parkinson's disease was practically withdrawn from the therapeutic arsenal. In the early 1970s, the follow-up examination of l-Dopa—treated patients began to reveal some drawbacks of the substitutive treatment such as intolerance, disappearance of efficacy, or even added complications such as abnormal involuntary movements, due not only to the evolution of the disease but also to the therapy itself. A recurrent need for surgical treatment was born and stereotactic procedures for thalamotomies were once again performed.9,30,32,33,85

To avoid surgical complications, accurate localization of the most effective target must be achieved during surgery, using electrophysiological methods: deep brain recordings3,4,35,82,91 aimed at the recognition of specific discharge patterns in the surrounding structures such as the ventroposterolateral (VPL) sensory thalamus in front of which is situated the VIM target or inside the VIM target itself.68,69,73,77 When electrical recording is not available, electrical stimulation can be used to detect areas surrounding the VIM nucleus that must be avoided, such as the sensory VPL nucleus or the pyramidal tract. During these procedures we observed that electrical stimulation was able to inhibit completely and immediately both parkinsonian rest tremor and postural tremor. However, this effect, which was immediately reversible when the stimulation was discontinued, was only obtained at high frequency (100 Hz and more). Similar observations have been previously reported: microelectrode recordings of neuronal activity in the human thalamus revealed the presence of burst discharges synchronous with tremor in VIM.3,5,38,39,46,63,72,93 These authors observed that stimulation at high frequency through the same microelectrode suppressed parkinsonian rest tremor immediately and that electrocoagulation within that area stopped tremor permanently.

We, as others,42,93 used this effect for several years as an intraoperative test for electrode placement. The implantation of a chronic deep brain stimulation (DBS) electrode was initially proposed as an experimental therapeutic procedure in a patient already thalamectomized on one side who persistently requested a contralateral procedure and who gave his informed consent.13 The result was excellent, and a pilot study of long-term high-frequency VIM stimulation in the treatment of disabling tremor was initiated for patients in whom a second operation contralateral to a previous thalamotomy was under consideration and for those in whom bilateral surgery was advocated.13–15 In view of the very encouraging results, we extended the method to other types of dyskinesias, including dystonias of various origins and multiple sclerosis tremor, to replace conventional destructive thalamotomy.16,77 We report here our experience with 117 consecutive patients implanted with uni- or bilateral electrodes in VIM (177 operated sides), with a follow-up period of more than 7 years (90 months) for the first patient. The absence of permanent complication, the minor side effects when any occurred and their immediate reversibility, the possibility of bilateral implantation in the same session, and the persistence of tremor relief are strong arguments that support chronic VIM stimulation as the method of choice when a surgical procedure is indicated for the treatment of Parkinson's disease and essential tremors and even more when a bilateral procedure is necessary.

Clinical Material and Methods
Patient Selection

From January 1987 to July 1994, 117 patients underwent implantation with uni- or bilateral electrodes (177 operated sides). Tremor amplitude at rest, during posture handling, or during action and intention maneuvers, was considered severe in all patients and scored as four of four on a five-point scale31 with an assessment of overall severity of four of four by both the patient and the examiner. This protocol received the approval of the Grenoble University Hospital ethical committee. All patients underwent a hospitalization period first during which they were evaluated.

Clinical Examination

Clinical examination was undertaken to confirm the diagnosis of tremor and its etiology. Quantification of the patients' symptoms was achieved by clinical measurements of frequency, amplitude, and type of the tremor and by videotaping. The tremor was also quantified by accelerometry. Neuropsychological evaluation was systematically performed, investigating global cognitive functions as well as frontal, attentional functions and motor neglect. In all patients, this evaluation protocol was performed again between the 3rd and 6th months after surgery.

Pharmacotherapeutic Test

All patients submitted to several pharmacological trials at the maximum tolerable dosages. Patients with Parkinson's received dopaminergic agonists plus peripheral decarboxylase inhibitors (l-Dopa up to 1100 mg/day; bromocriptine up to 30 mg/day; apomorphine up to 50 mg/kg per subcutaneous injection) and anticholinergic drugs (trihexylphenydyl up to 6 mg/day). Patients with essential tremor received propranolol up to 320 mg/day and primidone up to 750 mg/day. Patients who responded to medical therapy were not recommended for surgical intervention. The details of the population of patients are reported in Table 1.

TABLE 1

Description of patient population

DiseaseNo. of PatientsNo. of Bilat ImplantationNo. of Contralat ThalamotomyNo. of Bilat Surgery
Parkinson's disease8038846
essential tremor2013215
dyskinesia179413
total117601474

Parkinson's Disease, Essential Tremor, or Other Dyskinesias

There were 100 patients (with 151 implanted thalami) who exhibited either tremor due to Parkinson's disease (80 cases, 118 sides) or essential tremor (20 cases, 33 sides). Seventeen patients with 26 implanted thalami (four multiple sclerosis, five dystonias, one writer's cramp, seven posttraumatic or posthemorrhagic midbrain tremors) were operated on according to the same procedure. One patient with dystonia muscularis deformans was admitted to our service in critical condition, and the procedure was agreed upon with the patient's parents and medical team as a humanitarian therapeutic trial. This was later justified by the favorable outcome.

Surgical Procedures

After induction of brief, reversible general anesthesia (diprivan administered intravenously) spontaneously breathing patients were placed in a Talairach stereotactic frame (at the focus of a long distance (3.5 m) biorthogonal x-ray system). Anteroposterior and lateral x-ray films were obtained at an average magnification coefficient of 1.05. Contrast ventriculography was performed by freehand tapping of the frontal horn of the ventricle through a twist drill (90 mm from nasion, 25 mm from midline, 65 mm long Cushing cannula). Serial images were obtained during and after a 6.5-ml bolus injection of contrast medium (Iopamiron) with the patient supine and then prone. This allowed a very precise delineation of the midline of the third ventricle and of the anterior commissure (AC) and posterior commissure (PC).

The target of implantation has been VIM, considered to be the target for thalamotomy most effective in relieving tremor.36,62,66,69,71,73,76,77,93,94 The coordinates of VIM have been calculated from the lateral x-ray view according to a proportional geometric scheme based on the AC—PC line34,50,88 (Fig. 1A). The posterior and anterior limits of VIM on the AC—PC line are situated at the 2/12 and 3/12 of the AC-PC line length, ahead of the PC. The laterality of the theoretical target was equal to 11.5 mm from the lateral wall of the third ventricle.93 On the lateral view, the electrode projection was superimposed on the main axis of the VIM nucleus. After assessment in the initial cases, electrodes began to be placed more on the anterior than on the posterior border of the VIM, to diminish or even avoid the spreading of current to the primary somatosensory thalamic relay VPL, which induces contralateral paresthesias. On the anteroposterior view, the trajectory of the electrode was parallel to the midsagittal plane in 109 patients (162 electrodes). In eight patients (15 electrodes), an oblique trajectory was chosen (6°–10° from the mid-sagittal plane) to be aligned on the main axis of the VIM.

Fig. 1.
Fig. 1.

A: Schematic drawings over x-ray films for determination of the ventralis intermedius (VIM) target. The third ventricle dimensions did not significantly differ between Parkinson's disease, essential tremor, and dyskinesia groups. The anterior and posterior commissures (AC—PC) = 26.25 mm ± 2.02 mm. Thalamus height = 17.38 mm ± 1.76 mm. Third ventricle width at the level of electrode implantation = 6.69 mm ± 2.51 mm. B: Graphs showing general representation of the actual position of the monopolar VIM electrodes in the first 73 patients (108 thalami) and the active contacts of the tetrapolar VIM electrodes in the last 44 patients (69 thalami).

In the first 22 patients (28 sides), an electrode with an outer diameter of 2.3 mm (Radionics, Burlington, MA) was inserted into the VIM target through a 2.3-mm diameter burr hole and was used to stimulate structures during the electrode placement procedure. In the last 95 patients (149 sides), it was replaced by a semi-microelectrode69 or by a bipolar concentric stimulating-recording electrode with an outer diameter of 0.62 mm (model 17-300-1; Frederic Haer and Co., Brunswick, ME). Spontaneous as well as evoked multiunit activities were recorded at various sites along the trajectory down to the AC—PC line. The neuronal activity was recorded using conventional preamplifiers (model DAM-5A; World Precision Instruments, Hertfordshire, England), AC—DC amplifiers (Neurolog NL106; Digitimer Research Instruments, Hertfordshire, England), filters (Neurolog NL125; Digitimer Research Instruments), and spike triggers (Neurolog NL201; Digitimer Research Instruments), and then processed through a MacLab 4 WPI system and a MacIntosh II cx computer. Stimulation was also performed at various sites along the trajectory, using the same semimicroelectrode and a constant-current stimulator with an isolation unit (models Accupulser A310 and A365R; World Precision Instruments). The exact position of each recording and/or stimulating site was checked on x-ray film and imported into the final operating scheme. The effect of stimulation on tremor was quantified using an accelerometer attached to the patient's finger. Usually, several subsequent electrode tracks were performed parallel to the midsagittal plane and aimed at detecting the anterior and posterior limits of the VIM; these were also used to check the laterality. The expected effects of 130-Hz stimulation on tremor (tremor suppression with the lowest (0.2–2 mA) electrical intensity) was the major criterion in choosing the final placement of the chronic electrode. When they could be recorded, bursting cells synchronous to tremor were also considered to be a highly significant feature of the VIM. Finally, the body area in which paresthesias were induced by stimulation of VPL behind VIM could also help in defining the best laterality according to the known somatotopic organization, with lower-limb sensory neurons lying more laterally than hand and mouth neurons. Because of individual variations, the final target could therefore be significantly different from the theoretical target. When localization was considered satisfactory, the recording-stimulating electrode was removed and replaced by a chronic DBS electrode (Medtronic, Inc., Minneapolis, MN). The first 108 electrodes were monopolar (model SP5535; Medtronic, Inc.) with an insulated tip 1.2 mm in diameter and 4 mm long. The last 64 electrodes were tetrapolar (model 3387; Medtronic, Inc.) with four contacts 1.2 mm in diameter and 1.5 mm long each separated by 1.5 mm. The actual placement of electrodes in the 117 patients is reported on Fig. 1B. In both cases, this electrode was secured to the skull by a knot anchored in the bone and sealed by a drop of methylmethacrylate dental cement. This electrode was connected to a lead externalized through the skin at the level of the parietal area. All incisions were closed by nonresorbant sutures.

The patient was allowed to recover for 24 hours and then underwent test stimulation for approximately 1 week. When the test was considered satisfactory, a programmable stimulator (Itrel I in the first 23 patients and Itrel II in the last 94 patients; Medtronic, Inc.) was implanted in the subclavicular region on the same side as the electrode while the patient received general anesthetic. In patients undergoing bilateral operations, two stimulators allowed separate and independent stimulation of each VIM nucleus. All surgical procedures were performed without systemic antibiotic administration. Skin incisions were locally irrigated with rifampin during surgical procedure and prior to being closed.

Stimulation Parameters

During the stereotactic procedure, test stimulation was done with a 60-µsec pulse width frequency at 130 Hz and a current intensity that varied from 0.1 to 10 µA. The parameters of the implanted stimulator were set at 60-µsec pulse width, 130 Hz, and 0.5 to 8 volts. They were adjusted according to the needs of each patient during the follow-up period. If needed, the frequency range of the stimulator (Itrel II) could be extended to 185 Hz.

Evaluation of Benefits and Follow Up

After implantation of the stimulators, patients were kept at the hospital for 1 week to evaluate the effects of stimulation on the tremor. Video recordings as well as computerized tomography, magnetic resonance imaging, somatosensory evoked potentials, and in four cases, positron emission tomography evaluation of the cerebral blood flow28 were obtained. The clinical assessment of VIM stimulation effects was based on a five-point scale: 4 = complete disappearance of tremor in all circumstances; 3 = reappearance of a slight tremor on rare occasions (for example, under stress, mental calculation, or motor activation); 2 = moderate benefit; 1 = slight but definite benefit without any real improvement in daily living; and 0 = no benefit.

Results
Intraoperative Effects of VIM Stimulation

During insertion of the stimulating—recording test electrode (Fig. 2), stimulation at 130 Hz, 60-µsec pulse width was able to suppress the tremor with current intensities that decreased as long as the electrode approached the optimum site of stimulation, which usually corresponded to the VIM area, as determined by the scheme of Guiot and colleagues.34–36 The lowest value of this threshold was used to determine the site of maximum effectiveness into which the DBS electrode was finally implanted. Continuing progression of the electrode beyond this point usually necessitated increasing current values to suppress tremor, whereas permanent paresthesias actually induced by stimulation of VPL were progressively and more intensely induced. In the VIM area, stimulation with currents as low as 0.2 mA induced immediate suppression of the tremor, in a current intensity—dependent manner. At sufficient stimulation intensity, the tremor disappeared at the onset of the current, with no more than 1 or 2 seconds of delay, and recurred almost as immediately when the current was turned off. When a posteffect was observed, it did not last more than 10 to 20 seconds. The effect was polarity sensitive, the stimulating electrode being negative. When the polarity was reversed, the effect disappeared or at least was strongly decreased (Fig. 3). Brief paresthesias, which disappeared within 10 seconds, were often described by the patient at the onset of stimulation. During progression of the electrode toward the final target, a decrease in spontaneous tremor intensity was often observed, together with increased stimulation posteffects and difficulty in reinducing the tremor. This was considered a minor equivalent to the thalamotomy-like effect, which could be classically observed when entering the thalamotomy target with a larger electrode. In the VPL area, stimulation that was less effective in reducing tremor as the electrode was more distant from VIM somatotopically induced permanent paresthesias in various areas of the body.

Fig. 2.
Fig. 2.

Graph depicting the evolution of the current threshold along the electrode track, exploring the thalamus from anterior commissure (AC) to posterior commissure (PC), in 11 patients.

Fig. 3.
Fig. 3.

Electrophysiological recording showing effects of ventralis intermedius stimulation on the parkinsonian tremor in a representative patient and polarity dependence of stimulation-induced tremor suppression. The electrode penetration was anteroposteriorly into the right thalamus. The position of the electrode was −3 mm to the anterior and posterior commissure line and the stimulation intensity was 0.48 mA at 130 Hz. The tremor was recorded at the left index with an accelerometer. The accelerometric recording of tremor (upper trace) shows that negative polarity stimulation (lower trace) is more effective than positive polarity.

Extracellular Recording of Neuronal Activity

Neuronal activity was recorded along the track. With a semimacroelectrode, only multiunit activity was recorded: the amplitude of the spikes, described as “neural noise,”70,71 varied along the track and provided information about the limits of the different nuclei. This neural noise was high in the VIM and strongly diminished when the electrode entered the internal capsule (Fig. 4A). With the microelectrode, single units were recorded in the VIM and VPL. In the VIM, cells fired by bursts consisting of five to 10 large spikes, and some cells had a spontaneous bursting activity independent of any peripheral stimulation or muscular activity. Some other cells were definitely synchronous with the tremor (Fig. 4B and C) and also responded to passive movements of the limbs. Similarly, evoked activities were easily recorded in the VPL in response to superficial stimulation of the skin (touch, pressure) (Fig. 5).

Fig. 4.
Fig. 4.

Electrophysiological recordings in ventralis intermedius (VIM). A: Multiunit recording showing that the neural noise amplitude is high in the caudate nucleus (−23 mm from the anterior and posterior commissure line), then decreases (from −15 to −8 mm), and increases again when the electrode enters the VIM. B and C: Single-unit recordings (upper trace) of bursting cells recorded in the VIM (B) synchronous to tremor (accelerometry, lower trace). These cells are replaced by an electrical silence when the electrode leaves the VIM to enter the internal capsule (C).

Fig. 5.
Fig. 5.

Electrophysiological recordings in the ventroposterolateral sensory thalamus. Neural activity evoked by skin taps and light pressure was easily recorded.

Postoperative Effects of VIM Stimulation
Effects of VIM Stimulation on Tremor and Other Extrapyramidal Symptoms

Tremor was essentially the only symptom significantly influenced by VIM stimulation (Table 2). Rigidity was only slightly affected because the cogwheel syndrome was reduced when tremor was suppressed. There was almost no change in bradykinesia or in any other symptom of Parkinson's disease. Unilateral pain, which accompanied severe tremor and rigidity in many cases, also was greatly reduced.

TABLE 2

Effects of ventralis intermedius stimulation according to disease type*

 No. of Implanted Sides (%)
Score at ULFirst Follow Up (3 mos)Last Follow Up (at least 6 mos)
Parkinson's disease (111 electrodes) 
0 1 (0.9) 1 (0.9) 
1 3 (2.7) 5 (4.5) 
2 5 (4.5) 7 (6.3) 
3 31 (27.9) 55 (49.5) 
4 71 (64.0) 43 (38.7) 
global score (86) (83) 
essential tremor (36 electrodes) 
0 0 (0.0) 6 (16.7) 
1 3 (8.3) 2 (5.6) 
2 6 (16.7) 6 (16.7) 
3 13 (36.1) 18 (50.0) 
4 14 (38.9) 4 (11.1) 
global score (69) (59) 

Abbreviations: UL = upper limb; LL = lower limb.

The results are related to the number of implanted sides, because, in bilaterally implanted patients, they may be different from one side to the other. The global scores represent the evaluation of patients who had scores of 3 or 4 at both UL and LL (see Fig. 8), and this explains why the percentage of these scores is lower than the sum of scores 3 and 4 at the UL alone.

During the test period, the external extension of the DBS electrode was used to study the current threshold as a function of frequency, and this showed, as Fig. 6 demonstrates, that the optimum frequency was in the 100 Hz to 1000 Hz range with a minimum at approximately 250 Hz. In all patients, clinical modifications in the tremor were quite obvious: at the onset of stimulation, tremor disappeared within 2 seconds and remained absent provided that the intensity of the stimulation was sufficient. Discontinuation of stimulation always resulted in an immediate return of the tremor.

Fig. 6.
Fig. 6.

Graph depicting frequency—intensity relationship of the ventralis intermedius stimulation threshold for tremor suppression effect.

In patients with Parkinson's disease, drug therapy was often reduced after VIM stimulation: dopamine agonists were maintained in all but two patients to treat bradykinesia or to enhance the effects of VIM stimulation. Thirty-nine (48.7%) of 80 patients with Parkinson's disease had their dopamine dosage decreased by 20% at 3-month follow-up review, but only 12 (15%) at the last follow up continued at the decreased dosage, due to progression of the disease. Because stimulation effects were adjustable, results are given according to each patient's choice, based on an individual compromise between benefit and adverse effects.

During the initial postoperative period (3 months), scores of 3 or 4 were obtained in the upper limbs in 102 (91.9%) of the 111 operated sides (Table 2), whereas 7.2% of the sides had scores of 2 or 1, and 0.9% had a score of 0. At the last follow-up examination, these scores were 88%, 10.8%, and 0.9%, respectively. Global scores for the four limbs were slightly lower, rated 4 or 3 in 86% at 3 months and then 85% at the last follow up. Resting or postural tremor seemed to be better controlled than action tremor. In addition, distal limb tremor was more easily suppressed than proximal or axial tremor.

In patients with essential tremor, during the initial postoperative period, scores of 3 or 4 were obtained in the upper limbs in 27 (75%) of the 36 operated sides (Table 2), whereas 25% of the sides had scores of 2 or 1, and none had a score of 0. At the last follow up, these scores were obtained in 61.1%, 22.2%, and 16.7% of operated sides, respectively. Global scores for the four limbs were identical, as essential tremor involves mainly the upper limbs, rated 4 or 3 in 75% of operated sides at 3 months and then 61% at the last follow up.

Other kinds of dyskinesias (such as writer's cramp, posttraumatic dyskinesia, multiple sclerosis tremor, dystonias) were inconsistently, less significantly, or not improved. If improvement was achieved, it lasted only a few months. This is comparable to the results of thalamotomy.9,10 However, whereas the effects of VIM stimulation did not achieve a satisfactory result with regard to the clinical scoring scale used for tremor, there was significant improvement observed in the quality of daily living. In the two patients with familiar dystonia the parameters that proved to be the most effective were significantly different from those used in Parkinson's disease tremor and essential tremor, namely pulse width, which was 450 msec. The establishment of the effect was delayed, and the parameters had to be changed during rather long periods of observation to check the effects. When the stimulators were shut off or when the batteries were depleted, the patients' clinical status quickly worsened and the stimulators had to be changed immediately, after which it took several days for patients to recover to their previous clinical status. The effect of VIM stimulation in these two patients consisted mainly of a decrease in limb rigidity and in saliva inhalation, an increased facility in swallowing, and reduction in hip, knee, and elbow flexed positions, all leading to a global improvement in general status. Two of the four multiple sclerosis patients had a good or fair benefit.

Side Effects

Side effects were always reversible, mild, and accepted, as long as VIM stimulation intensity could be set at a level at which these side effects became tolerable for the patient and tremor relief was still good or excellent. Paresthesias (9%) were usually induced at intensities of stimulation higher than those that suppressed the tremor and lasted a few minutes or even seconds after the onset of VIM stimulation. However, they were much less intense when electrode placement was more anterior, close to the anterior border. These paresthesias were never painful except in one patient whose electrode was placed 2 mm below the AC—PC line and who experienced burning sensations in the perioral and ophthalmic area. These disappeared when the electrode was withdrawn 2 mm. Higher amplitudes than those needed to suppress tremor could result in the induction of a slight cerebellar dysmetria interpreted as a spreading of current to cerebellar pathways. In 9% of patients, a dystonia of the foot was observed after approximately 12 months of stimulation. This was reversible when stimulation was discontinued but resumed immediately at onset and therefore required the patients to use slightly lower parameters to avoid this dystonia. Dysarthria was observed in 23 patients (19.6%; 18 Parkinson's disease, five essential tremor): only five (4.2%) had unilateral stimulation, 14 (12%) had bilateral stimulation, and four (3.4%) had a previous contralateral thalamotomy. When compared to the numbers of patients in each group, dysarthria was observed in 14 (27.5%) of the 51 bilaterally stimulated patients but in four (40%) of the 10 patients who underwent thalamotomy on one side and stimulation on the other side. This shows that thalamotomy has more side effects than VIM stimulation. Disequilibrium was observed in 10 patients (six Parkinson's disease, four essential tremor), of whom six were bilaterally and four unilaterally stimulated, among whom three had previous contralateral thalamotomy. Contralateral dystonia was observed in six patients (four Parkinson's disease, two essential tremor), of whom four were bilaterally stimulated and two unilaterally. Bilateral stimulation induced perioral paresthesias in one patient with Parkinson's disease and hypersalivation in one patient with essential tremor. Bilateral stimulation did not induce the neuropsychological deficits usually reported following bilateral thalamotomies. No patient spontaneously complained of symptoms of frontal disturbance, but neuropsychological tests showed a slight, lateralized decrease in performance fluency, especially affecting verbal performance, when the left VIM was stimulated, and spatial performance, when the right VIM was stimulated. Detailed results will be reported elsewhere.

Follow-Up Data on VIM Stimulation Parameters

In 22 (20.5%) of 107 patients and 23 (15%) of 153 electrodes, introduction of the test electrodes during the procedure induced total suppression of the tremor when the electrode reached the target. Assessment of the efficacy of external stimulation had to be delayed in many patients because of temporary suppression or reduction of the tremor induced by the microthalamotomy-like effect of electrode implantation. The tremor reappeared after 1 to 10 days, in many cases at a lower amplitude than before surgery. This “target impact effect” (or thalamotomy-like effect) usually disappeared within 1 week and the tremor resumed. Nevertheless, in all cases the intensity of VIM stimulation necessary to alleviate tremor had to be increased during the first 3 weeks from an average initial value of 1 V ± 0.5 V to approximately 4 V ± 0.5 V. It reached a plateau after approximately 2 months at a mean value of 3.06 V (Fig. 7A). Using the Itrel II stimulators, it was possible to measure the electrical impedance of the brain structures stimulated by the implanted electrode. This parameter increased significantly during the first days, from a mean of 794 ohm (range 499–1238 ohm) on Day 14 and then more slowly during the following weeks to 1057 ohm (range 828–1483 ohm) on Day 106 (Fig. 7B). This increase in impedance could account, at least in part, for the increase in threshold current intensity observed during clinical follow up of treated patients. The average current charge density with the first electrodes (DBS SP 5535; Medtronic) (60-msec pulse width, 130 Hz) was 2.89 mA/16.2 mm2 = 179 A/m2.

Fig. 7.
Fig. 7.

Graphs showing the evolution of the intensity of ventralis intermedius stimulation required to suppress totally the tremor with time (A), and the evolution of electrode impedance measured on Itrel II stimulators (B).

The effect of VIM stimulation (Fig. 8) remained stable more often in patients with Parkinson's disease (96% of the 102 stimulated sides) than in patients with essential tremor (81% of the 27 stimulated sides), although essential tremor is considered to be the best indication for thalamotomy:36 complete suppression of the tremor was achieved with rather low stimulation voltages, which were stable after the initial postoperative increase. Discontinuation of VIM stimulation led to a recurrence of the tremor almost identical to that observed during the preoperative test period.

Fig. 8.
Fig. 8.

Bar graphs showing clinical results for Parkinson's disease, essential tremor, and dyskinesia patients, expressed in percentage versus the clinical status, rated at 3 months after surgery (initial) and at the last follow up (final).

However, in 36% of cases (two of 20 with essential tremor, 33 of 78 with Parkinson's disease), discontinuation of the VIM stimulation resulted in a rebound effect, consisting of an increased intensity in the tremor as compared to the preoperative intensity. Patients who previously had no tremor while sleeping then required VIM stimulation 24 hours a day, because their tremor without stimulation had increased to a level that did not allow them to fall asleep. Sixty-four percent of patients (18 of 20 with essential tremor, 45 of 78 with Parkinson's disease) were able to stop their stimulator at night.

In four (44%) of the nine patients who had an initial score at 4 or 3 and were then rated at 2 or 1 at their last follow up, improvement in the activities of daily life was still significant. This was mainly the case for Parkinson patients with rest tremor, and this loss of efficacy appeared at 17.2 ± 9.6 months.

In five (55%) of these nine patients, this decrease in score was no longer associated with a significant functional improvement. These were primarily patients with an action component to their tremor, and this loss of efficacy appeared more quickly, at 7.2 ± 1.5 months postoperatively.

Mortality and Morbidity

There was no operative mortality. One patient died suddenly on the 11th postoperative day from pulmonary embolism due to previously existing cardiovascular insufficiency, although he had recovered from stereotactic surgery and was able to walk into the neurosurgery department. Five others died from various nonneurological diseases at 3, 6, 7, 10, and 23 months. In six patients, a microhematoma was induced by electrode insertion: three were asymptomatic, discovered only on routine postoperative computerized tomography scanning, two were responsible for transient motor neglect, and one occurred in a patient with multiple sclerosis and induced an acute deficit on the 8th day, also reversible in 3 months. Five patients suffered from skin problems: three had a late scalp infection, due to skin necrosis in front of the cable connectors in two female patients with thin scalps. In these three cases, electrode and connector removal and further replacement were needed to heal the wounds. Two patients had a granuloma along the connector extension track, and one patient had transient fluid collection in the subclavicular pocket of the stimulator. In this series no epileptic seizures were induced by thalamic kindling. There was no complication of ventriculography. This procedure is safe when strict landmarks are observed, and reported complications are often due to use of cannulas longer than 65 mm.21,55 Comparable low morbidity has been already observed during VPL chronic stimulation for pain.1,43

Discussion

The intraoperative suppressive effect of thalamic stimulation on parkinsonian tremor has long since been reported in the same site in which thalamotomy would also suppress tremor.6,8,42,63,76,80,92,93 It has also been reported that stimulation increased or triggered the tremor.66,69 Dependence on the effect of frequency was observed,64 but it was not clearly established that high frequency was a critical parameter, although in some reports6 this stimulation was performed at 200 Hz. Surprisingly, attempts to apply this observation as a permanent treatment were rare, reported as poorly effective and short lived92 or involving the centrum medianum and the intralaminar nuclei,11,12,64 zona incerta,19 the sensory VPL nucleus,25,58,64,84 the pulvinar and dentate nucleus,61 but not the VIM nucleus.

Efficacy of VIM Stimulation on Tremor Arrest

As a general rule, the effectiveness of VIM stimulation reproduces that classically obtained for thalamotomy: Parkinson's disease tremor and essential tremor are the best indications, and complete arrest can be expected when the patients are carefully selected and the surgical stereotactic procedure is correctly performed. The results are immediate, spectacular, and totally reversible without significant posteffect and without permanent side effect. However, this effect is selective, as the different effects of VIM stimulation on Parkinson's disease tremor, essential tremor, and other dyskinesias suggest that the corresponding underlying mechanisms are also different, at least with regard to the role of the VIM.

Reduced Morbidity of Unilateral and Bilateral VIM Stimulation

Because the procedure is safe and devoid of tissue destruction after electrode insertion, it minimizes the risk of bleeding or progressive edema. The procedure was always well tolerated, even by the oldest patient who was 81 years old. Bilateral implantation during one surgical session (in 60 of 117 patients; 51%) or complementary implantation on the contralateral side of a previous contralateral thalamotomy (in 14 of 117 patients; 11.9%) did not induce any of the neuropsychological deficits frequently reported in cases of bilateral thalamotomy. This, by itself, is a unique advantage of VIM stimulation and provides a surgical solution for patients in whom bilateral thalamotomy would be indicated. Because the side effects are immediately reversible, the patient has the opportunity to choose between the benefit of VIM stimulation, which suppresses the tremor, and the eventual side effect, or simply to lower the intensity of stimulation to the level at which the side effects are reduced and the benefit still significant.

Tolerance Phenomenon in VIM Stimulation

In this series, stimulation amplitude had to be increased in all patients. The initial increase was more rapid during the first 3 weeks and was related to tissue changes around the electrode. The need for the late increase in stimulation amplitude was because of the progression of Parkinson's disease or the development of tolerance. The first hypothesis could explain the late recurrences of tremor several months after thalamotomy, although this does not really happen when placement of the lesion has been correct.29,36 The second hypothesis assumes that chronic stimulation of the VIM nucleus would become less effective with time, therefore demanding an ever increasing amplitude of stimulation. The observed increase in electrode impedance can account only for the early and not the late tolerance to VIM stimulation. Tolerance was not due to depletion of the power batteries: after changing the generator parameters were not significantly different. The Itrel I stimulators have already been replaced in 15 of 19 patients after 34 ± 15 months (range 17–63 months). The life time of the four Itrel I stimulators not yet replaced ranges from 56 to 80 months. Four Itrel II stimulators have already been replaced, with a life time of 41.8 ± 7.7 months (range 31–49 months). The life time of the 77 Itrel II stimulators not yet changed ranges from 1.9 to 56 months. Tolerance could also be due to a decreased biological response (habituation) of the neuronal network. This hypothesis is supported by the fact that after turning off VIM stimulation, the tremor recurred with a temporary rebound of its amplitude. The threshold intensity for alleviation of tremor had to be regularly increased up to a final level that could no longer be increased due to the induction of paresthesias. This led to a loss of functional benefit, mainly in patients with intense initial tremor who needed high intensities 24 hours a day. This tolerance was reversible after a stimulation holiday when VIM stimulation arrest was acceptable by the patient. A similar phenomenon has been observed during central gray matter stimulation for pain.43

Mechanism of Action

The intimate mechanisms underlying the effect of VIM stimulation are unknown as, too, are the mechanisms of tremor65,74,75 and remain to be studied. It is surprising that both destruction and stimulation of the same structure achieve the same effect. Actually, VIM stimulation suppresses tremor only when the frequency of stimulation is at least 100 Hz (Fig. 6). The similarity of this curve with that commonly known as the intensity—frequency relationship recorded in frog muscle nerve fibers26 is striking. This suggests, by analogy, that VIM stimulation involves mostly passing fibers rather than cell bodies of VIM neurons.

This paradoxical effect of stimulation when using low-frequency versus high-frequency currents has been also reported during stimulation of the intralaminar and midline thalamic nuclei for relief of epilepsy in human patients98 and has long been known and documented in experimental animals.2,41,44,47,60 The precise structure that is stimulated in our series is more than probably the VIM, although no anatomical control is available. During thalamotomy, it has been already observed that stimulation in the VIM can suppress tremor and that coagulation at that site will achieve the same effect.6,11,92,93 The anatomical landmarks from the third ventricular commissures are accurate when a proportional graphic system is used to construct the position of the target.88,97 The pattern of semimicroelectrode recording cannot fully characterize VIM. Detection of the best target using the changes in neural noise69,71,73,76,77 can be equivocal. Observation of rhythmic patterns in the VIM3–6,68,69,71,73,76,93 is not always easy to achieve. Recognition of the specific somatosensory areas of the thumb and labial commissure in VPL immediately behind the VIM target seems to be a reliable landmark5,29,36 and is a strong argument for the identification of the effective target as the VIM, and not the VPL. In our last 72 cases in which a preliminary electrode track crossed the VIM from front to back, the stimulation threshold required to suppress tremor was minimal in the area corresponding to the geometrically defined VIM from the AC—PC landmarks of Guiot, et al.,34 (Fig. 2) and significantly reincreased when the electrode entered the VPL, where the threshold of induced paresthesias was in turn minimal. Therefore, our target is definitely situated immediately in front of the VPL and is more than likely the VIM.

Role of VIM Nucleus in the Arrest of Tremor During Thalamic Stimulation

Knowledge of the afferent and efferent connections of the VIM and of the biochemical basis of Parkinson's disease does not provide an explanation for this mechanism. The VIM probably receives vestibular afferents37 as well as proprioceptive inputs from limbs76–78 and projects onto the motor cortical area.49 However, there are three main populations of cells that are situated successively and encountered by the electrode along a track passing through the reticular thalamic nucleus, the ventrooral anterior and ventroposterior parts of the ventrolateral nucleus, and then the VIM.78 In the reticular thalamic nucleus, cells respond to verbal command; in the ventrooral—ventroposterior parts of the ventrolateral nucleus and the VIM, the populations of cells responding to voluntary and passive movements are mixed, and the rhythmic activities recorded at these levels either precede or follow the motor activity recorded by electromyographic (EMG) monitoring.4–6,54,76,78 It can be assumed that the VIM is a proprioceptive relay,7,68 receiving postural inputs from the peripheral joints and muscles. It is also suggested that the VIM can trigger tremor. Rhythmic activities, recorded in VIM cells of patients17,46,73,78,93 preceding EMG discharges and disappearing just before tremor arrest, are not suppressed in monkeys with tremor by section of the dorsal spinal roots67 or after injection of curare.48,52 Therefore, the VIM would act as part of a feed-back loop,81 impinging on the main corticospinal motor pathway and aiming at modulation of the transfer function of the sensorimotor system. The gain in this loop can be regulated by other afferents, among which the dopaminergic nigrostriatal system presumably plays a key role.79 Deletion of this dopaminergic control would detune the VIM-containing loop and therefore lead to a noncritically dampened loop responsible for the oscillatory behavior that is constitutive of the tremor. Interruption of this ill-regulated feed-back loop (by destruction or by stimulation-induced inhibition of the VIM) would suppress this abnormally oscillatory behavior (and then suppress the tremor) but would also suppress a normally needed tuning system, thus explaining why voluntary movement after thalamotomy is never as precise and skilled as it is in normal persons. On the basis of the studies of motor activities under the effect of DBS in humans, it has been proposed that resonance properties of the motor control circuit are basic features of the motor system, which are normally dampened by a suppression mechanism. When this mechanism weakens, external stimuli or internal impulses may elicit oscillations and then tremor. This model does not postulate a thalamic rhythmic center to explain the tremorogenic process.95 Jamming of the VIM, in this hypothesis, would also result in the same tremor suppression. However, this cannot be a unique system because we did not have such good results in other types of dyskinesias (17 patients with 26 thalamic-implanted sides). It may be possible that the VIM is not an adequate target for these dyskinesias and has to be replaced by a more appropriate structure, which has yet to be discovered. For instance, stimulation of a target, which is 8 mm below and 2.5 mm more medial than ours, has been reported to be effective on multiple sclerosis intention tremor,19 compared with the lack of satisfactory and long-lasting results in our series for this type of dyskinesia. However, tremor in multiple sclerosis may be of various origins—cerebellar or extrapyramidal—depending on the location of the responsible sclerotic lesion. Therefore, VIM stimulation may suppress the extrapyramidal component of the tremor and leave the other component unaffected, in particular the cerebellar tremor. Ventralis intermedius stimulation has to be compared to the VIM thalamotomy, which is commonly reported to be effective regardless of the type of dyskinesia, although clinical description of patients as well as precisely evaluated postoperative scores are not often available in the neurosurgical literature.86

Assuming that the data obtained in the monkey45,49,96 on afferent and efferent connections of the thalamus could be extrapolated to humans,49 one might consider that the VIM has strong reciprocal connections from the cerebellum,53 whereas the VPL receives the somatosensory lemniscal projections and the ventroposterior part of the ventrolateral nucleus receives mainly pallidal inputs. When the electrode is correctly placed in the medial part of the VIM or even better in its anterior half, immediately behind the posterior limit of the ventroposterior part of the ventrolateral nucleus, the tremor-suppressing effect is consistently obtained at low thresholds and is free from any side effects. In these ideal cases, when the intensity of stimulation is increased purposely, for as long as the patient feels it is acceptable, the appearance of cerebellar symptoms such as a dysmetria during the finger-to-nose maneuver and hypotonia can be observed.

Conclusions

In our experience VIM stimulation is a remarkable therapeutic agent against the tremor of Parkinson's disease as well as essential tremor, although it is much less effective in other types of dyskinesias. This method should therefore be applied after careful clinical analysis of the patient's case. Ventralis intermedius stimulation is effective at high frequency. Good results are strongly correlated with accurate placement of electrodes. Additional electrophysiological methods such as microstimulation and recording must be used to locate the target precisely and to achieve the best placement. Criteria such as the intensity of neural noise, the close vicinity of the thumb—labial commissure sensory representation in the VPL, as well as recording of cells bursting synchronously with tremor, are valuable tools. The types of dyskinesias that do not respond to VIM stimulation depend on other targets that remain to be discovered. The lack of permanent side effects and, moreover, the possibility of performing bilateral implantations in one session without any permanent neuropsychological side effect are the most important arguments in support of this method. This method can be proposed systematically as a first alternative, even if thalamotomy later becomes necessary at the same site, which never occurred in our experience. The cost of the procedure has to be taken into consideration. Finally, the mechanism of action is still unknown, and if the hypothesis of a high frequency—induced inhibition or jamming accounts for the observed effects, a precise explanation is still needed, which might also help in avoiding the phenomenon of tolerance. Ventralis intermedius stimulation is increasingly used as a treatment for tremor,83 of l-Dopa induced dyskinesias,18 of persistent hemiballism (T Tsubokawa, et al., unpublished data), and might have other effects than tremor suppression.20 Moreover, this procedure does not exclude the patient from consideration for another type of treatment such as fetal transplant in the future. It therefore appears that VIM stimulation can be proposed as a standard neurosurgical approach to tremor, with the same indications as those imposed for thalamotomy. Finally, VIM stimulation provides an experimental opportunity, because of its reversibility and adjustability, to study and understand the mechanisms of tremor in Parkinson's disease as well as of normal motor control in humans.

Acknowledgments

The authors thank Dr. Elizabeth Boogusch for useful help with the English text and Mrs. A. Abbadie for typing the manuscript.

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    Sanderson PMavoungou RAlbe-Fessard D: Changes in substantia nigra pars reticulata activity following lesions of the substantia nigra pars compacta. Neurosci Lett 67:25301986Neurosci Lett 67:

  • 80.

    Schaltenbrandt GSpuler HWahren Wet al: Electroanatomy of the thalamic ventro-oral nucleus based on stereotaxic stimulation in man. Z Neurol 199:2592761971Z Neurol 199:

  • 81.

    Schnider SMKwong RHKwan HCet al: Detection of feedback in the central nervous system of parkinsonian patients. IEEE WA 11:2912941986IEEE WA 11:

  • 82.

    Sem-Jacobsen CW: Depth-electrographic observations related to Parkinson's disease. Recording and electrical stimulation in the area around the third ventricle. J Neurosurg 24:3884021966Sem-Jacobsen CW: Depth-electrographic observations related to Parkinson's disease. Recording and electrical stimulation in the area around the third ventricle. J Neurosurg 24:

  • 83.

    Siegfried J: Chronic electrical stimulation of the VL-VPL complex and of the pallidum in the treatment of extrapyramidal and cerebellar disorders: personal experience since 1985XIIth Meeting of the World Society for Stereotactic and Functional Neurosurgery. Abstract 125Ixtapa, Mexico1993 [Unverified]

  • 84.

    Siegfried J: Effets de la stimulation du noyau sensitif du thalamus sur les dyskinésies et la spasticité. Rev Neurol 142:3803831986Siegfried J: Effets de la stimulation du noyau sensitif du thalamus sur les dyskinésies et la spasticité. Rev Neurol 142:

  • 85.

    Siegfried J: Neurosurgical treatment of Parkinson's disease. Present indications and valueRinne UKKlingler MStamm G (eds): Amsterdam: Elsevier1979369376

  • 86.

    Speelman JD: Parkinson's Disease and Stereotaxic Neurosurgery. Thesis. Amsterdam: Rodopi1991218Speelman JD: Parkinson's Disease and Stereotaxic Neurosurgery.

  • 87.

    Stellar SCooper IS: Mortality and morbidity in cryothalamectomy for parkinsonism. A statistical study of 2868 consecutive operations. J Neurosurg 28:4594671968J Neurosurg 28:

  • 88.

    Talairach JDavid MTournoux Pet al: Atlas d'Anatomie Stéréotaxique des Noyaux Gris Centraux. Paris: Masson1957294 [Unverified]Atlas d'Anatomie Stéréotaxique des Noyaux Gris Centraux.

  • 89.

    Talairach Jde Ajuriaguerra JDavid M: A propos des coagulations thérapeutiques sous-corticales: étude topographique du système ventriculaire en fonction des noyaux gris centraux. Presse Med 58:6977011950Presse Med 58:

  • 90.

    Talairach JHecaen HDavid Met al: Recherches sur la coagulation thérapeutique des structures sous-corticales chez l'homme. Rev Neurol 81:4241949Rev Neurol 81:

  • 91.

    Taren JGuiot GDerome Pet al: Hazards of stereotaxic thalamectomy. Added safety factor in corroborating X-ray target localization with neurophysiological methods. J Neurosurg 29:1731821968J Neurosurg 29:

  • 92.

    Tasker R: Effets sensitifs et moteurs de la stimulation thalamique chez l'homme Applications cliniques. Rev Neurol 142:3163261986Tasker R: Effets sensitifs et moteurs de la stimulation thalamique chez l'homme Applications cliniques. Rev Neurol 142:

  • 93.

    Tasker RROrgan LWHawrylyshyn P: Investigation of the surgical target for alleviation of involuntary movement disorders. Appl Neurophysiol 45:2612741982Appl Neurophysiol 45:

  • 94.

    Tasker RRSiquiera JHawrylyshyn Pet al: What happened to Vim thalamotomy for Parkinson's disease? Appl Neurophysiol 46:68831983Appl Neurophysiol 46:

  • 95.

    Toth SSolyom AVajda Jet al: The rhythmic properties of the motor system. Stereotact Funct Neurosurg 53:951041989Stereotact Funct Neurosurg 53:

  • 96.

    Van Buren JMBorke RCModesti LM: Sensory and nonsensory portions of the nucleus “ventralis posterior” thalami of the chimpanzee and man. J Neurosurg 45:37481976J Neurosurg 45:

  • 97.

    Velasco FVelasco MOgarrio Cet al: Electrical stimulation of the centromedian thalamic nucleus in the treatment of convulsive seizures: a preliminary report. Epilepsia 28:4214301987Epilepsia 28:

This study was supported by INSERM, CNAMTS, Grenoble University, Région Rhone-Alpes, France Parkinson, Fondation pour la Recherche Medicale and Joseph Fourier University. Dr. Gao received a fellowship from Jinzhou University and later Grenoble University.

This work was presented in part at the 60th annual meeting of the American Association of Neurological Surgeons in San Francisco, California, April 11–16, 1992.

Article Information

Address reprint requests to: Alim Louis Benabid, M.D., Department of Clinical and Biological Neurosciences, INSERM Pre-clinical Neurobiology U-318, Joseph Fourier University of Grenoble, Hôpital A. Michallon, Pavilion B, BP 217, 38043 Grenoble, France.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    A: Schematic drawings over x-ray films for determination of the ventralis intermedius (VIM) target. The third ventricle dimensions did not significantly differ between Parkinson's disease, essential tremor, and dyskinesia groups. The anterior and posterior commissures (AC—PC) = 26.25 mm ± 2.02 mm. Thalamus height = 17.38 mm ± 1.76 mm. Third ventricle width at the level of electrode implantation = 6.69 mm ± 2.51 mm. B: Graphs showing general representation of the actual position of the monopolar VIM electrodes in the first 73 patients (108 thalami) and the active contacts of the tetrapolar VIM electrodes in the last 44 patients (69 thalami).

  • View in gallery

    Graph depicting the evolution of the current threshold along the electrode track, exploring the thalamus from anterior commissure (AC) to posterior commissure (PC), in 11 patients.

  • View in gallery

    Electrophysiological recording showing effects of ventralis intermedius stimulation on the parkinsonian tremor in a representative patient and polarity dependence of stimulation-induced tremor suppression. The electrode penetration was anteroposteriorly into the right thalamus. The position of the electrode was −3 mm to the anterior and posterior commissure line and the stimulation intensity was 0.48 mA at 130 Hz. The tremor was recorded at the left index with an accelerometer. The accelerometric recording of tremor (upper trace) shows that negative polarity stimulation (lower trace) is more effective than positive polarity.

  • View in gallery

    Electrophysiological recordings in ventralis intermedius (VIM). A: Multiunit recording showing that the neural noise amplitude is high in the caudate nucleus (−23 mm from the anterior and posterior commissure line), then decreases (from −15 to −8 mm), and increases again when the electrode enters the VIM. B and C: Single-unit recordings (upper trace) of bursting cells recorded in the VIM (B) synchronous to tremor (accelerometry, lower trace). These cells are replaced by an electrical silence when the electrode leaves the VIM to enter the internal capsule (C).

  • View in gallery

    Electrophysiological recordings in the ventroposterolateral sensory thalamus. Neural activity evoked by skin taps and light pressure was easily recorded.

  • View in gallery

    Graph depicting frequency—intensity relationship of the ventralis intermedius stimulation threshold for tremor suppression effect.

  • View in gallery

    Graphs showing the evolution of the intensity of ventralis intermedius stimulation required to suppress totally the tremor with time (A), and the evolution of electrode impedance measured on Itrel II stimulators (B).

  • View in gallery

    Bar graphs showing clinical results for Parkinson's disease, essential tremor, and dyskinesia patients, expressed in percentage versus the clinical status, rated at 3 months after surgery (initial) and at the last follow up (final).

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83.

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92.

Tasker R: Effets sensitifs et moteurs de la stimulation thalamique chez l'homme Applications cliniques. Rev Neurol 142:3163261986Tasker R: Effets sensitifs et moteurs de la stimulation thalamique chez l'homme Applications cliniques. Rev Neurol 142:

93.

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94.

Tasker RRSiquiera JHawrylyshyn Pet al: What happened to Vim thalamotomy for Parkinson's disease? Appl Neurophysiol 46:68831983Appl Neurophysiol 46:

95.

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96.

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97.

Velasco FVelasco MOgarrio Cet al: Electrical stimulation of the centromedian thalamic nucleus in the treatment of convulsive seizures: a preliminary report. Epilepsia 28:4214301987Epilepsia 28:

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