Chronic Subthalamic Nucleus Stimulation Research Articles

Long-term efficacy of deep brain stimulation of the subthalamic nucleus in patients with pharmacologically intractable epilepsy: a case series of six patients.

Epilepsy is one of the widespread neurological illnesses, and about 20-40% of epilepsy patients are pharmacoresistant. We aimed to assess the long-term efficacy of subthalamic nucleus (STN) deep brain stimulation (DBS) for drug-resistant epilepsy. We included pharmacologically intractable epilepsy patients who had STN-DBS at the Chinese People's Liberation Army General Hospital between June 2016 and December 2018. We retrospectively evaluated pre- and postoperative clinical outcomes, including seizure frequency, seizure type, anti-seizure medication, cognitive function, anatomical target coordinates, stimulation parameters, and adverse events following the surgical procedure. Six patients with a mean follow-up of 49.3 ± 10.2 months, were included. Seizure frequency decreased by an average of 64.0% after STN-DBS at last year follow-up (p = 0.046), and one patient (1/6) achieved seizure-free status. For seizure type, anti-seizure medication, and cognitive function, there were no significant differences between pre-and post-operation (p > 0.05). In terms of stimulation parameters, the pulse width, amplitude, and frequency were 58.3 ± 9.4 μsec, 2.5 ± 0.7 V, and 122.5 ± 15.7 Hz, respectively. None of the patients showed normal electroencephalography during the electroencephalography reexamination. There were no surgery-related complications, and chronic STN stimulation was generally well tolerated in five patients. However, one patient (1/6) had a difficulty of dyskinesia in the right arm. In conclusion, neuromodulation of the STN by DBS is a promising option for patients with pharmacologically intractable epilepsy, especially for whose epileptic zone originates mainly from the frontoparietal region and who are unsuitable for resective surgery. Further prospective multicenter studies with a larger sample size are necessary for further exploration.

Apathy in Parkinson's Disease: Clinical Patterns and Neurobiological Basis.

Apathy is commonly defined as a loss of motivation leading to a reduction in goal-directed behaviors. This multidimensional syndrome, which includes cognitive, emotional and behavioral components, is one of the most prevalent neuropsychiatric features of Parkinson's disease (PD). It has been established that the prevalence of apathy increases as PD progresses. However, the pathophysiology and anatomic substrate of this syndrome remain unclear. Apathy seems to be underpinned by impaired anatomical structures that link the prefrontal cortex with the limbic system. It can be encountered in the prodromal stage of the disease and in fluctuating PD patients receiving bilateral chronic subthalamic nucleus stimulation. In these stages, apathy may be considered as a disorder of motivation that embodies amotivational behavioral syndrome, is underpinned by combined dopaminergic and serotonergic denervation and is dopa-responsive. In contrast, in advanced PD patients, apathy may be considered as cognitive apathy that announces cognitive decline and PD dementia, is underpinned by diffuse neurotransmitter system dysfunction and Lewy pathology spreading and is no longer dopa-responsive. In this review, we discuss the clinical patterns of apathy and their treatment, the neurobiological basis of apathy, the potential role of the anatomical structures involved and the pathways in motivational and cognitive apathy.

Prediction of Movement Ratings and Deep Brain Stimulation Parameters in Idiopathic Parkinson’s Disease

BackgroundDeep brain stimulation (DBS) parameter fine-tuning after lead implantation is laborious work because of the almost uncountable possible combinations. Patients and practitioners often gain the perception that assistive devices could be beneficial for adjusting settings effectively. ObjectiveWe aimed at a proof-of-principle study to assess the benefits of noninvasive movement recordings as a means to predict best DBS settings. Materials and MethodsFor this study, 32 patients with idiopathic Parkinson’s disease, under chronic subthalamic nucleus stimulation with directional leads, were recorded. During monopolar review, each available contact was activated with currents between 0.5 and 5 mA, and diadochokinesia, rigidity, and tapping ability were rated clinically. Moreover, participants’ movements were measured during four simple hand movement tasks while wearing a commercially available armband carrying an inertial measurement unit (IMU). We trained random forest models to learn the relations between clinical ratings, electrode settings, and movement features obtained from the IMU. ResultsFirstly, we could show that clinical mobility ratings can be predicted from IMU features with correlations of up to r = 0.68 between true and predicted values. Secondly, these features also enabled a prediction of DBS parameters, which showed correlations of up to approximately r = 0.8 with clinically optimal DBS settings and were associated with congruent volumes of tissue activated. ConclusionMovement recordings from customer-grade mobile IMU carrying devices are promising candidates, not only for remote symptom assessment but also for closed-loop DBS parameter adjustment, and could thus extend the list of available aids for effective programming beyond imaging techniques.

Chronic Subthalamic Nucleus Stimulation in Parkinson's Disease: Optimal Frequency for Gait Depends on Stimulation Site and Axial Symptoms.

Axial symptoms emerge in a significant proportion of patients with Parkinson's disease (PD) within 5 years of deep brain stimulation (STN-DBS). Lowering the stimulation frequency may reduce these symptoms. The objectives of the current study were to establish the relationship between gait performance and STN-DBS frequency in chronically stimulated patients with PD, and to identify factors underlying variability in this relationship. Twenty-four patients treated chronically with STN-DBS (>4 years) were studied off-medication. The effect of stimulation frequency (40–140 Hz, 20 Hz-steps, constant energy) on gait was assessed in 6 sessions spread over 1 day. Half of the trials/session involved walking through a narrow doorway. The influence of stimulation voltage was investigated separately in 10 patients. Gait was measured using 3D motion capture and axial symptoms severity was assessed clinically. A novel statistical method established the optimal frequency(ies) for each patient by operating on frequency-tuning curves for multiple gait parameters. Narrowly-tuned optimal frequencies (20 Hz bandwidth) were found in 79% of patients. Frequency change produced a larger effect on gait performance than voltage change. Optimal frequency varied between patients (between 60 and 140 Hz). Contact site in the right STN and severity of axial symptoms were independent predictors of optimal frequency (P = 0.009), with lower frequencies associated with more dorsal contacts and worse axial symptoms. We conclude that gait performance is sensitive to small changes in STN-DBS frequency. The optimal frequency varies considerably between patients and is associated with electrode contact site and severity of axial symptoms. Between-subject variability of optimal frequency may stem from variable pathology outside the basal ganglia.

Diurnal Variation of Hypothalamic Function and Chronic Subthalamic Nucleus Stimulation in Parkinson's Disease

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) improves quality of life in patients with advanced Parkinson's disease (PD), but is associated with neuropsychiatric side effects and weight gain in some individuals. The pathomechanisms of these phenomena are still unknown. Considering anatomical and functional connections of the STN with the hypothalamic-pituitary (HP) system, we prospectively investigated whether chronic STN-DBS alters HP functioning in 11 PD patients. Methods: Basal hormone levels of the HP-adrenal (HPA), HP-gonadal and HP-somatotropic axis were determined before surgery as well as 3 and 6 months after electrode implantation. In addition, 24-hour cortisol profiles and dexamethasone suppression tests were obtained. Postoperative hormone changes were correlated with individual neuropsychological test performance, psychiatric status and anthropometric measures. Results: While PD patients experienced weight gain (p = 0.025) at follow-up, most neuropsychological data and basal HP hormone levels did not change over time. HPA regulation and diurnal rhythmicity of cortisol remained intact in all patients. The 24-hour mean cortisol levels decreased 6 months after surgery (p = 0.002) correlating with improved postoperative depression (p = 0.02). Conclusions: Chronic application of high-frequency electrical stimuli in the STN was not associated with HP dysfunction in patients with advanced PD. The diurnal variability of peripheral cortisol secretion as one important element of the endogenous biological clock remained intact. Evening cortisol levels decreased after surgery reflecting a favorable regulation of the cortisol setpoint. STN-DBS can be considered safe from a neuroendocrine perspective, but the origin of unwanted side effects warrants further elucidation.

Effect of deep brain stimulation on speech in Parkinson's disease: From research lab to clinic

Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN), an evidence-based, effective surgical treatment with increasing popularity, can help patients with advanced Parkinson's disease eliminate or lessen many of the motor symptoms they experience. However, one of its unfortunate adverse effects is that it may worsen existing speech impairment as well as causing new impairment. As a result, the patients may be unable to speak loudly or clearly, or simply unable to initiate speech. The problems often associate with active as well as chronic STN stimulation. Further, there does not seem to be a uniform effect on different speech subsystems of respiration, phonation, and articulation. In this presentation, we will first review studies which have shown differential effects on phonation, articulation, and prosody associated with unilateral vs. bilateral STN DBS. Next, we will discuss the preliminary outcomes of several potential treatment approaches and strategies including the Lee Silverman voice treatment, change of DBS settings, and the altered auditory feedback. Lastly, we will discuss our experience of using the approaches and strategies helping patients with their speech deficits associated with STN DBS in clinical settings. Both mechanisms and limitations will be explored.

Effects of five years of chronic STN stimulation on muscle strength and movement speed

This study examined the long-term effects of chronic subthalamic nucleus (STN) deep brain stimulation (DBS) using both clinical evaluation and laboratory motor control measures. Over a 5-year time period, changes in the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) and movement speed and strength at the ankle joint were evaluated on and off STN DBS in eight patients with Parkinson's disease (PD). Four patients were also studied at the elbow joint. Patients with PD originally received unilateral STN DBS between years 2001 and 2003. They were re-evaluated after 5 years of long-term STN DBS between years 2006-2008. At baseline (year 0) and after 5 years, patients with PD were tested off treatment and on STN DBS. In each testing condition, patients performed ballistic, single degree of freedom ankle dorsiflexion and ankle plantarflexion movements and peak velocity was calculated. Patients also performed maximal voluntary contractions at the ankle joint in both directions, and peak torque was calculated. Results showed increased motor UPDRS scores from year 0 to year 5, but STN DBS was efficacious in reducing them. In contrast to the increase in motor UPDRS scores, motor control results showed a marked improvement in peak velocity and peak torque over the 5-year time period in the off treatment condition, and STN DBS was efficacious by improving both peak velocity and peak torque. The current findings suggest that 5 years of chronic STN DBS can have beneficial effects on the motor system over the long term in discrete motor tasks in which maximal effort and maximal neural output is required.

Management of antiparkinsonian therapy during chronic subthalamic stimulation in Parkinson's disease

Objective This article reports the detailed analysis of antiparkinsonian drug therapy in 78 consecutive Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) of the subthalamic nucleus (STN). Methods: The amount and type of antiparkinsonian drugs – including l-dopa, dopamine receptor agonists, associated drugs such as catechol-O-methyl transferase and monoamine oxidase inhibitors, amantadine and anticholinergics – were quantified before surgery and at two control visits 1 and 3 years following chronic STN stimulation. Results The l-dopa mean daily dose was reduced by approximately 60% after 1 year and remained stable after 3 years. Apomorphine, bromocriptine, tolcapone and selegiline were withdrawn after STN-DBS. Three years postoperatively, 9 patients (11.5%) no longer required l-dopa and 6 patients (7.7%) completely stopped all dopaminergic medications. More patients were on monotherapy with either l-dopa or dopamine receptor agonist, and fewer patients required combined treatment of dopamine receptor agonist and l-dopa compared with the pre-surgical condition. Conclusions Dopaminergic drug treatment is persistently reduced and simplified following chronic STN-DBS for up to 3 years.

Replacement of dopaminergic medication with subthalamic nucleus stimulation in Parkinson's disease: Long‐term observation

Stimulation of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson's disease (PD), but the medication requirements after implant are poorly known. We performed a long-term prospective evaluation of 20 patients maintained at stable dopaminergic therapy for 5 years after bilateral STN implants, who were evaluated 6 months, 1 year, 3 years, and 5 years after surgery. We measured, during the entire observation period, the effect of deep brain stimulation on motor and functional outcome measures, the levodopa equivalent daily dose and the total electrical energy delivered. At 5 years, the UPDRS motor score had improved by 54.2% and levodopa equivalent dose was reduced by 61.9%, compared with preimplant. Dopaminergic medication remained stable during the observation period, but energy was progressively increased over time. Rest tremor, rigidity, gait, lower and upper limb akinesia, and total axial score were improved in decreasing order. Postural stability and speech improved transiently, whereas on-period freezing of gait, motor fluctuations and dyskinesias recovered durably. Functional measures did not show improvement in autonomy and daily living activities after STN implant. Chronic STN stimulation allows to replace for dopaminergic medications in the long-term at the expense of an increase of the total energy delivered. This is associated with marked improvement of motor features without a matching benefit in functional measures.

The subthalamic nucleus is a key-structure of limbic basal ganglia functions

Among the basal ganglia nuclei, the subthalamic nucleus has a major function in the motor cortico-basal ganglia-thalamo-cortical circuit and is a target site for neurosurgical treatment such as parkinsonian patients with long-term motor fluctuations and dyskinesia. According to animal and human studies, the motor functions of the subthalamic nucleus have been well documented whereas its implication on limbic functions is still less well understood and is only partially explained by anatomical and functional theories of basal ganglia organisation. After chronic subthalamic nucleus stimulation in patients with Parkinson's disease, many studies showed executive impairments, apathy, depression, hypomania, and impairment of recognition of negative facial emotions. The medial tip of the subthalamic nucleus represents its limbic part. This part receives inputs from the anterior cingulate cortex, the medial prefrontal cortex, the limbic part of the striatum (nucleus accumbens), the ventral tegmental area and the limbic ventral pallidum. The medial tip of the subthalamic nucleus projects to the limbic part of the substantia nigra and the ventral tegmental area. We propose a new function scheme of the limbic system, establishing connections between limbic cortical structures (medial prefrontal cortex, amygdala and hippocampus) and the limbic part of the basal ganglia. This new circuit could be composed of a minor part based on the model of cortico-basal ganglia-thalamo-cortical loop, and of a major part linking the subthalamic nucleus with the mesolimbic dopaminergic pathway via the ventral tegmental area and the nucleus accumbens, and with limbic cortical structures. This scheme could explain limbic impairments after subthalamic nucleus stimulation by disruption of limbic information inside the subthalamic nucleus and the ventral tegmental area.

Outcome of Bilateral Subthalamic Nucleus Stimulation in the Treatment of Parkinson’s Disease: Correlation with Intra-Operative Multi-Unit Recordings but Not with the Type of Anaesthesia

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) gained general acceptance in the treatment of Parkinson’s disease (PD). Objective: To study the clinical outcome and the predicting factors of efficacy of chronic STN stimulation, while DBS electrodes were implanted under local or general anaesthesia with intra-operative electrophysiological guidance based on multi-unit recordings. Methods: We included a large single-centre cohort of 54 patients with advanced PD (mean age: 59 years; disease duration: 14 years). Clinical evaluation was performed by the Unified Parkinson’s Disease Rating Scale (UPDRS) before and 1 year after surgical placement of DBS electrodes. Results: In the on-stimulation and off-medication condition, the UPDRS part III score was reduced by 56% compared to the off-stimulation condition or pre-operative off-drug score. In the on-stimulation and on-medication condition, this score was reduced by 73%. The severity of motor fluctuations and dyskinesia (UPDRS part IV) and the activities of daily living (UPDRS part II) were reduced by 65 and 80%, respectively, in the on-stimulation/on-medication condition compared to the pre-operative baseline. The daily dose of antiparkinsonian treatment was diminished by 72%. Among the various pre- and intra-operative data, the most important predictive factor for clinical efficacy of STN stimulation was the length of hyperactivity along the best track observed in intra-operative multi-unit recordings. Other predictive factors included age, disease duration and pre-operative levodopa responsiveness or baseline off-drug values of the Hoehn and Yahr and UPDRS part III scores. In contrast, the type of anaesthesia (local vs. general) did not significantly influence the clinical outcome. Conclusion: The present results are in the average of previously published results, but they have been obtained from a large single-centre cohort of patients with important reductions in the daily dose of antiparkinsonian drugs. This study confirmed the efficacy of the STN-DBS technique and emphasized the value of an original intra-operative electrophysiological approach based on multi-unit and not single-unit quantified recordings. This method allows DBS electrode implantation to be safely performed under general anaesthesia without lessening the rate of efficacy of the procedure.

Pathological gambling in Parkinson's disease improves on chronic subthalamic nucleus stimulation

Pathological gambling (PG) related to dopaminergic treatment in Parkinson's disease (PD) is part of a spectrum of behavioral disorders called the dopamine dysregulation syndrome (DDS). We describe a series of PD patients with preoperative active PG due to dopaminergic treatment from a total of 598 patients who have undergone surgery for subthalamic nucleus stimulation for disabling motor fluctuations. The patients had systematic open assessment of behavioral symptoms and standardized assessments of motor symptoms, mood, and apathy. Seven patients (6 men, 1 woman; age, 54 +/- 9 years; levodopa equivalent dose, 1,390 +/- 350 mg/day) had preoperative PG over a mean of 7 years, intolerant to reduction in medication. Six had nonmotor fluctuations and four had other behavioral symptoms consistent with a diagnosis of the DDS. After surgery, motor symptoms improved, allowing for 74% reduction of dopaminergic treatment, below the dosage of gambling onset. In all patients, PG resolved postoperatively after 18 months on average (range, 0-48), although transient worsening occurred in two. Improvement paralleled the time course and degree of reduction in dopaminergic treatment. Nonmotor fluctuations, off period dysphoria, and other symptoms of the DDS improved. Two patients developed persistent apathy. In conclusion, PG and other symptoms of the DDS-associated dopaminergic treatment improved in our patients following surgery. Dopaminergic dysregulation commonly attributed to pulsatile overstimulation of the limbic dopaminergic system may be subject to desensitization on chronic subthalamic stimulation, which has a relative motor selectivity and allows for decrease in dopaminergic treatment.

Cognitive outcome 5 years after bilateral chronic stimulation of subthalamic nucleus in patients with Parkinson’s disease

Aim: To assess the long-term cognitive and behavioural outcome after bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients affected by Parkinson’s disease, with a 5-year follow-up...

Can chronic subthalamic nucleus stimulation induce de novo tremor in Parkinson's disease?

Subthalamic nucleus stimulation dramatically improves parkinsonian symptoms, notably the tremor. The occurrence of a tremor in the first 6 months after the surgical procedure in patients without tremor preoperatively is much less common. We report on the cases of 3 patients who developed such modification of their parkinsonian symptomatology. Physiopathological hypotheses are discussed.

Deep Brain Stimulation for Parkinson’s Disease: Association between Stimulation Parameters and Cognitive Performance

Chronic subthalamic nucleus stimulation produces inconsistent patterns of cognitive change in Parkinson’s disease patients. Individually tailored stimulation parameters may contribute to this variable pattern of change. Systematic variation of amplitude, pulse width, and rate of stimulation has been reported to produce unique changes in motor and limbic response. To evaluate the association between stimulation parameters and cognitive/behavioral response, neuropsychological performance and stimulation parameter data of 8 Parkinson’s disease patients were submitted to Pearson r correlation analysis. Results indicate that each stimulation parameter was significantly associated with a subset of measures. The current findings raise the possibility that adverse cognitive/behavioral responses may be treated through parameter modification while maintaining motor symptom efficacy.

Effects of Subthalamic Nucleus Stimulation on Urodynamic Findings in Patients with Parkinson’s Disease

Although the effects of subthalamic nucleus stimulation on the control of motor symptoms in patients with Parkinson's disease have been demonstrated, to our knowledge there are no data on effects of this treatment on voiding. We evaluated differences in urodynamic findings in patients with Parkinson's disease during on and off subthalamic nucleus stimulation status. We evaluated 3 males and 2 females with Parkinson's disease. All patients had undergone surgical bilateral implantation of subthalamic nucleus electrodes 4 to 9 months before our observation. Urodynamic evaluation was performed during chronic subthalamic nucleus stimulation and 30 minutes after turning off the stimulators. Certain parameters were evaluated, including bladder compliance and capacity, first desire to void volume, bladder volume of appearance (reflex volume) and amplitude of detrusor hyperreflexic contractions, maximum flow, detrusor pressure at maximum flow and detrusor-sphincter coordination. Results were compared statistically. Statistically significant differences in urodynamic data obtained during on and off subthalamic nucleus stimulation status were noted. In particular bladder capacity and reflex volume were increased for on status (median 320 versus 130 ml., p = 0.043 and 250 versus 110, p = 0.043, respectively). The amplitude of detrusor hyperreflexic contractions was decreased for on status but the difference was not significant (median 23 versus 37 cm. H2O, p = 0.223). No differences were noted in the other urodynamic parameters considered during the filling and voiding phases. Our experience shows that subthalamic nucleus stimulation seems to be effective for decreasing detrusor hyperreflexia in Parkinson's disease cases. This finding confirms a role for basal ganglia in voiding control.

Results of chronic subthalamic nucleus stimulation for Parkinson’s disease: a 1-year follow-up study

BACKGROUND Deep brain stimulation (DBS) has been established as an alternative approach for the treatment of advanced Parkinson’s disease (PD). Recently, the subthalamic nucleus (STN) has been identified as the optimal target for DBS. METHODS Thirty-eight patients have undergone surgery for advanced PD since 1996. They include 12 females and 26 males with a mean age of 55.6 years. The mean stage on the Hoehn and Yahr Scale was 3.5 (off condition). Electrodes (Medtronic DBS 31389) were stereotactically implanted into the STN bilaterally. Targeting was performed using computerized tomography (CT) scans and ventriculography (VG). After 4 days of external stimulation, permanent neurostimulators were implanted. Patients were evaluated preoperatively and 1, 6, and 12 months postoperatively. Evaluations were performed in defined on and off states using the Unified Parkinson’s Disease Rating Scale (UPDRS) as well as the Hoehn and Yahr Scale, the dyskinesia scale, and the Activities of Daily Living (ADL) Scale. RESULTS Significant improvement of all motor symptoms was found in all patients (UPDRS motor score 32/48 preoperatively versus 15/30 at 12-month follow-up, p < 0.001). Daily off-times were reduced by 35%. Dyskinesias also improved markedly (UPDRS IV: 3.2/3.1 [on/off] vs. 0.9/1.3 at 12 months follow-up). Postoperative L-dopa medication was adjusted (mean reduction: 53%). Complications occurred in two patients (5%) who developed infections, leading to system removal. Systems were replaced after 6 months. Two patients (5%) had a permanent worsening of a previously known depressive state and developed progressive dementia. CONCLUSION STN stimulation is a relatively safe procedure for treating advanced PD. The possibility of readjusting the stimulation parameters postoperatively improves the therapeutic outcome and reduces side effects in comparison to ablative methods.

Chronic stimulation of subthalamic nucleus improves levodopa-induced dyskinesias in Parkinson's disease

Ventroposterior pallidotomy, and pallidal and subthalamic nucleus (STN) stimulation, are proposed to treat severe Parkinson’s disease (PD) with levodopa-induced motor complications. Pallidal surgery decreases levodopa-induced dyskinesias (LID). Parkinsonism evaluated by the motor part of the Unified Parkinson’s Disease Rating Scale (UPDRS) improves by about 30% after unilateral pallidotomy. STN stimulation can greatly improve parkinsonian disability, but its effects on LID are unknown because the first patients treated with STN stimulation were selected with mild or absent LID since spontaneous STN lesions can induce hemiballism. However, our initial experience with STN stimulation showed that stimulation-induced abnormal movements could be controlled by setting the stimulation voltage below the dyskinesia threshold. Moreover, the substantial decrease in levodopa dosage, which was made possible by the antiparkinsonian benefit, allowed a decrease in LID in the long-term. Thus, STN stimulation was also proposed for patients with severe LID. We selected all consecutive patients with young-onset PD, since this population is generally levodopa-sensitive and prone to develop severe LID. Eight patients with a mean age of 51 (SD 10) years and a mean disease duration of 16 (5) years were operated on bilaterally in the STN because of severe motor fluctuations (motor score on the UPDRS 57·5 [14·5] off-drug and 18·2 [10·6] on-drug). The study was approved by the Grenoble University ethical committee and all patients gave their written, informed consent. The surgical procedure has been described previously. 6 months after surgery, the motor score of the UPDRS improved from 58 (16) to 17 (8) (–71%) in the off-drug condition when stimulation was switched on. This improvement was seen in all the major parkinsonian symptoms. The dyskinesia score (six body parts, each scored 0–4, maximum score 24), assessed during the maximum motor response of a levodopa test with the same dose as preoperatively (early morning +50–100 mg), decreased from 11·4 (6·6) preoperatively to 6·8 (4·3) postoperatively onstimulation. Dyskinesia duration and disability (UPDRS items 32+33), which assess LID during activities of daily living under chronic stimulation, decreased from 4·0 (1·9) to 1·4 (0·9) (–65%). The antiparkinsonian drug dosage calculated as levodopa equivalent decreased from 1560 (930) to 680 (420) mg daily (–56%). With chronic STN stimulation, LID were greatly improved, in a similar percentage as with bilateral globus-pallidusinternus stimulation. With unilateral pallidotomy, contralateral LID are substantially improved although a big reduction of levodopa is not possible. Targeting the STN instead of the globus pallidus internus has the advantage of inducing a more pronounced antiakinetic effect. The decrease in LID induced by STN stimulation can be explained mainly by the decrease in levodopa dosage. This is why the improvement in dyskinesias is more obvious in activities of daily living than during the levodopa test with a dose identical to that given before surgery. Moreover, as highfrequency stimulation is supposed to act through neuroinhibition, the chronic inhibition of STN neurons can change the dyskinesia threshold with time, in the same way as the progressive abatement of hemiballism after a vascular lesion of the STN. Replacing the pulsatile levodopa-induced decrease of STN activity by a chronic stable decrease seems to improve dyskinesias. After 4 years of experience of STN stimulation, this surgical treatment improves LID with time, contrary to our initial fears. As the improvement in all the main parkinsonian motor symptoms is substantial in patients with a good levodopa response, the STN is suggested as the target of choice for the neurosurgical treatment of PD, even in patients with severe LID. However, randomised studies comparing different surgical procedures are required to better understand their respective value.