Effect of bilateral subthalamic electrical stimulation in Parkinson’s disease

doi:10.1016/S0090-3019(01)00533-X

Surgical Neurology

Volume 56, Issue 2, August 2001, Pages 89-94

https://doi.org/10.1016/S0090-3019(01)00533-X Get rights and content

Abstract

BACKGROUND

Bilateral high frequency subthalamic stimulation has been reported to be effective in the treatment of Parkinson’s disease and levodopa-induced dyskinesias. To analyze the results of this surgical procedure we critically reviewed 17 parkinsonian patients with advanced disease complicated by motor fluctuations and dyskinesias.

METHODS

Between January 1998 and June 1999 these 17 consecutive patients (age 48–68 years; illness duration 8–27 years) underwent bilateral stereotactically guided implantation of electrodes into the subthalamic nucleus in the Department of Neurosurgery of the Istituto Nazionale Neurologico “C. Besta.” Parameters used for continuous high-frequency stimulation were: frequency 160 Hz, pulse width 90 μsec, mean amplitude 2.05 ± 0.45 V. Parts II and III of the UPDRS were used to assess motor performance before and after operation by the neurologic team. The follow-up ranged between 6 and 18 months.

RESULTS

At latest examination, mean UPDRS II and III scores had improved by 30% (on stimulation, off therapy) with mean 50% reduction in daily off time. Peak dyskinesias and early morning dystonias also improved in relation to therapy reduction. Side effects were persistent postoperative supranuclear oculomotor palsy and postural instability in one case, worsened off-medication hypophonia in three, and temporary nocturnal confusion episodes in three. Postoperative MRI revealed a clinically silent intracerebral haematoma in one case. One electrode required repositioning.

CONCLUSIONS

Continuous high frequency STN stimulation is an effective treatment for advanced PD. A functionally useful and safe electrode placement can be performed without microrecording.

Section snippets

Patients

Between January 1998 and June 1999 17 consecutive patients (age 48–68 years; illness duration 8–27 years) underwent bilateral stereotactically guided implantation of electrodes into the subthalamic nucleus at the Department of Neurosurgery of the Istituto Nazionale Neurologico “C. Besta.” Baseline clinical data are shown in Table 1. All had advanced PD with severe motor fluctuations and dyskinesias despite treatment with levodopa and dopamine agonists. No other neurological impairment was

Results

Mean scores in the UPDRS part II (Table 2) and III (Table 3) significantly improved after surgery. Table 4 summarizes the improvements in parts II and III of UPDRS on and off medication while being stimulated. The percentage improvement was greatest (around 50%) in activities of daily living (part II) when the patients were on medication and on stimulation, while the improvement was around 30% for UPDRS parts II and III off medication and on stimulation.

The most remarkable result was the

Discussion

Our results confirm that continuous high-frequency STN stimulation may improve all parkinsonian motor signs and levodopa-induced motor complications, even in cases of advanced disease with severe motor fluctuations and dyskinesias. Although there were large between-subject variations, all patients in this series benefited significantly from electrode implantation (Figure 1) and STN stimulation. The most striking finding in our patients was that both “off” time and dyskinesias were reduced after

Conclusions

Continuous high-frequency STN stimulation is an effective treatment for advanced PD. Functionally useful and safe electrode placement can also be performed without microrecording [15]. In our experience, it reduced the severity of parkinsonian signs and levodopa-related dyskinesias, the latter sometimes improving before levodopa reduction. The best results are obtained in younger, levodopa-responding patients, but a mild improvement, positively affecting the quality of life, may be observed

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Cited by (30)

Bilateral subthalamic nucleus stimulation in the treatment of advanced Parkinson's disease. Five years' personal experience
2010, Neurologia i Neurochirurgia Polska
Citation Excerpt :
Deep brain stimulation (DBS), especially deep brain stimulation of the subthalamic nucleus (STN DBS), is an established procedure in the treatment of advanced Parkinson disease (PD) complicated by levodopa-induced dyskinesia. Many reports confirm the efficacy of bilateral STN DBS in short-term as well as long-term follow-up [1–24]. The advantage of STN DBS is the possibility to perform the procedure simultaneously, which ameliorates parkinsonian symptoms on both sides of the body [7,21,24].
The objective of the study was to assess bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) for patients with advanced Parkinson disease (PD).
The study population included 5 patients with bilateral STN DBS who completed a 5-year postoperative follow-up period. In all patients electrodes (Model 3387 or 3389) were stereotactically bilaterally inserted into the STN using a Leksell stereotactic G frame. The clinical rating tests included Unified Parkinson's Disease Rating Scale (UPDRS) and two motor-timed tests derived from CAPIT (rapid movements between two points and stand-walk-sit test). All patients were assessed in off and on condition before implantation and 1, 3 and 5 years in medication on and off condition and stimulation on condition and stimulation off condition. To compare preoperative to postoperative UPDRS scores, only mean values and standard deviations are presented because of the small study population.
The stimulation effect was noted in the off state, resulting in a 59% improvement in motor scores of UPDRS at 5-year follow-up, when compared to preoperative scores. In the on state the stimulation improved motor scores by 17%. At 5-year follow-up, reduction of daily levodopa dose was 50%.
Bilateral STN DBS is an effective and safe treatment for patients with advanced PD. Bilateral STN DBS contributes to improvement of parkinsonian symptoms in the off state and levodopa-induced dyskinesia. This can be correlated with a 50% reduction of daily levodopa dose 5 years postoperatively.
Celem pracy była ocena skuteczności obustronnej głębokiej stymulacji jądra niskowzgórzowego (subthalamic nucleus – STN) w leczeniu zaawansowanej postaci choroby Parkinsona (ChP).
Badany materiał kliniczny stanowiła grupa 5 chorych poddanych obustronnej stymulacji STN, u których czas pooperacyjnej obserwacji wynosił co najmniej 5 lat. U wszystkich chorych wszczepiono obustronnie elektrody do głębokiej stymulacji STN (Model 3387 lub 3389) z zastosowaniem ramy stereotaktycznej Leksell G. Kliniczną ocenę stanu chorych przeprowadzono za pomocą Ujednoliconej Skali Oceny Choroby Parkinsona (UPDRS) i dwóch testów ruchowych CAPIT (szybkie ruchy pomiędzy dwoma punktami oraz test chodu). Pacjentów oceniono w fazie off i on przed operacją oraz po upływie roku, 3 i 5 lat w fazie off i on w czasie stymulacji i przy włączeniu generatorów impulsów. Do oceny różnic pomiędzy pomiarami przedoperacyjnymi i pomiarami pooperacyjnymi według UPDRS podano wartości średnie i odchylenia standardowe ze względu na niewielką liczbę badanych chorych.
Wpływ stymulacji odnotowano w fazie off, co spowodowało zmniejszenie nasilenia objawów ruchowych o 59% w 5-letnim okresie pooperacyjnym w porównaniu z wartościami przedoperacyjnymi. W fazie on efekt stymulacji przyczynił się do zmniejszenia objawów ruchowych ChP o 17%. Pięć lat po operacji odnotowano zmniejszenie dobowej dawki lewodopy o 50%.
Obustronna stymulacja STN jest najbezpieczniejszą i najskuteczniejszą metodą leczenia chorych z zaawansowaną ChP. Obustronna stymulacja STN przyczynia się do ustąpienia objawów fazy off i dyskinez pląsawiczych, co związane jest z 50-procentowym zmniejszeniem dobowej dawki lewodopy w obserwacji 5-letniej.
Subthalamic nucleus stimulation affects subjective emotional experience in Parkinson's disease patients
2009, Neuropsychologia
A number of studies have reported impaired facial emotion recognition following subthalamic nucleus (STN) stimulation in Parkinson's disease (PD), and have related these changes to a limbic dysfunction induced by STN stimulation. The present study examined the effect of STN stimulation in PD patients on a specific component of emotion, namely the subjective experience of emotion. Thirteen post-operative PD patients, 13 pre-operative PD patients matched on clinical and neuropsychological characteristics, and 16 controls matched on age and education, were administered a validated battery of film excerpts known to primarily induce specific emotional feelings (anger, happiness, sadness, fear, disgust, and neutral), and self-rated the intensity of their emotional feelings on a discrete emotions questionnaire. The post-operative group showed a significant lower level of differentiation between the target feeling (i.e., the more likely to be reported) and non-target feelings for the film excerpts intended to induce “sadness” and “fear” respectively, as compared with the pre-operative and healthy control groups. Moreover, the post-operative group reported significantly less intense feelings of fear, anxiety and disgust for the excerpt intended to induce “fear” as compared with the pre-operative and the control groups, while no significant difference was observed between the pre-operative and control groups. Finally, the post-operative group reported significantly less intense feelings of sadness and anxiety during the excerpt intended to induce “sadness” as compared to the control group, although the differences between the pre- and post-operative groups and between the pre-operative and the control groups did not reach significance. Our study suggests that STN stimulation affects the subjective experience of emotion, thus providing a preliminary account of the modulation induced by STN stimulation of a distributed neuronal network underlying the subjective experience of emotion, although the exact contribution of the STN within such network remains to be specified.
Fast-Track Programming and Rehabilitation Model: A Novel Approach to Postoperative Deep Brain Stimulation Patient Care
2007, Archives of Physical Medicine and Rehabilitation
Citation Excerpt :
In stage I, quadripolar DBS electrodes (model 3389)a are implanted bilaterally using CT and MRI fusion and microelectrode recording for electrophysiologic target confirmation. Our surgical technique followed closely the methods for microrecording and electrode implantation that have been published elsewhere.4-9 Stage I was performed under local anesthesia with minimal intravenous sedation.
Cohen DB, Oh MY, Baser SM, Angle C, Whiting A, Birk C, Whiting DM. Fast-track programming and rehabilitation model: a novel approach to postoperative deep brain stimulation patient care.
To propose a new model of integrated, multidisciplinary postoperative care of the patients with deep brain stimulation (DBS).
Observational cohort study with follow-up at 3 months and 1 year.
Academic medical center movement disorder clinic.
Seventy-three consecutive patients with medically refractory Parkinson’s disease underwent bilateral DBS. Patients were then transferred directly to an inpatient rehabilitation facility.
DBS and inpatient programming and rehabilitation. Simultaneous programming and rehabilitation was carried out by a multidisciplinary team.
The FIM instrument, Unified Parkinson Disease Rating Scale (UPDRS), and levodopa dosage.
The average rehabilitation stay was 17.3 days, with a mean of 6.2 stimulator adjustments during that time. FIM scores improved from 62.1 (admission) to 98.5 (discharge), an average improvement of 36.4 (58.6%). Average UPDRS scores improved from 52.5 (preoperative off) and 30.1 (preoperative on) to 20.4 (3mo postoperative on-medication, on-stimulation), a 32.2% improvement from the preoperative on score. Levodopa dosages decreased by an average of 48.3% (all P<.001).
We describe our fast-track protocol, which allows for rapid DBS programming and tapering of Parkinson’s medications. It also provides for treatment of concomitant medical and psychologic problems and optimized physical performance.
Deep brain stimulation
2007, Handbook of Clinical Neurology
Citation Excerpt :
Figure 43.4. summarizes 39 clinical studies of STN DBS in advanced PD, reporting on a total of 1129 patients (Moro et al., 1999; Pinter et al., 1999; Houeto et al., 2000; Molinuevo et al., 2000; Broggi et al., 2001; Katayama et al., 2001; Krause et al., 2001; Lopiano et al., 2001; The Deep‐Brain Stimulation for Parkinson's Disease Study Group, 2001; Volkmann et al., 2001; Doshi et al., 2002; Figueiras‐Mendez et al., 2002; Iansek et al., 2002; Kleiner‐Fisman et al., 2002; Lanotte et al., 2002; Martinez‐Martin et al., 2002; Ostergaard et al., 2002; Romito et al., 2002b; Simuni et al., 2002; Tavella et al., 2002; Thobois et al., 2002; Valldeoriola et al., 2002; Vesper et al., 2002; Vingerhoets et al., 2002; Herzog et al., 2003b; Krack et al., 2003; Landi et al., 2003; Pahwa et al., 2003; Tamma et al., 2003; Varma et al., 2003; Esselink et al., 2004; Ford et al., 2004; Jaggi et al., 2004; Peppe et al., 2004; Capecci et al., 2005; Lyons and Pahwa, 2005; Minguez‐Castellanos et al., 2005; Rodriguez‐Oroz et al., 2005; Visser‐Vandewalle et al., 2005). The median improvement in the UPDRS motor score in the off‐period was 50.2% (lower quartile 42%, upper quartile 60.8%) More specifically, improvement is seen in off‐phase akinesia, rigidity, tremor (Krack et al., 1998c; Rodriguez et al., 1998), gait (Allert et al., 2001; Faist et al., 2001; Stolze et al., 2001) and balance.
Deep brain stimulation (DBS) is considered a highly effective therapy for all cardinal symptoms of Parkinson's disease (PD) and levodopa-induced motor complications. DBS is based on the empirical observation that high-frequency electrical stimulation of specific brain targets can mimic the effect of a lesion without the need for destroying brain tissue. DBS is accomplished by permanently implanting an electrode into the target area and connecting it to an internal pulse generator. The stimulator settings can be adjusted telemetrically with respect to electrode configuration, current amplitude, pulse width, and pulse frequency. DBS essentially mimics the clinical effects of lesioning in all three target structures currently used for the treatment of PD―namely, ventrolateral thalamus, internal pallidum, and subthalamic nucleus (STN), when high-frequency (> 100 Hz) stimulation (HFS) is applied. DBS is considered an alternative for ablative stereotactic surgery in movement disorders with several advantages, such as: (1) DBS does not require a destructive lesion to be made in the brain, (2) DBS can be performed bilaterally with relative safety, (3) stimulation parameters can be adjusted postoperatively to improve efficacy, to reduce adverse effects, and to adapt DBS to the course of disease, and (4) DBS is reversible and does not preclude the use of possible future therapies in PD requiring integrity of the basal ganglia circuitry.
Subthalamic nucleus neurones in slices from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mice show irregular, dopamine-reversible firing pattern changes, but without synchronous activity
2006, Neuroscience
The loss of dopamine in idiopathic or animal models of Parkinson’s disease induces synchronized low-frequency oscillatory burst-firing in subthalamic nucleus neurones. We sought to establish whether these firing patterns observed in vivo were preserved in slices taken from dopamine-depleted animals, thus establishing a role for the isolated subthalamic–globus pallidus complex in generating the pathological activity.
Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) showed significant reductions of over 90% in levels of dopamine as measured in striatum by high pressure liquid chromatography. Likewise, significant reductions in tyrosine hydroxylase immunostaining within the striatum (>90%) and tyrosine hydroxylase positive cell numbers (65%) in substantia nigra were observed. Compared with slices from intact mice, neurones in slices from MPTP-lesioned mice fired significantly more slowly (mean rate of 4.2 Hz, cf. 7.2 Hz in control) and more irregularly (mean coefficient of variation of inter-spike interval of 94.4%, cf. 37.9% in control). Application of ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonopentanoic acid (AP5) and the GABA_A receptor antagonist picrotoxin caused no change in firing pattern. Bath application of dopamine significantly increased cell firing rate and regularized the pattern of activity in cells from slices from both MPTP-treated and control animals. Although the absolute change was more modest in control slices, the maximum dopamine effect in the two groups was comparable. Indeed, when taking into account the basal firing rate, no differences in the sensitivity to dopamine were observed between these two cohorts. Furthermore, pairs of subthalamic nucleus cells showed no correlated activity in slices from either control (21 pairs) or MPTP-treated animals (20 pairs). These results indicate that the isolated but interconnected subthalamic–globus pallidus network is not itself sufficient to generate the aberrant firing patterns in dopamine-depleted animals. More likely, inputs from other regions, such as the cortex, are needed to generate pathological oscillatory activity.
Location of the active contact within the subthalamic nucleus (STN) in the treatment of idiopathic Parkinson's disease
2004, Surgical Neurology
Chronic electrical stimulation of the subthalamic nucleus (STN) has been shown to be safe and effective in the treatment of medically refractory idiopathic Parkinson's disease. The clinically most relevant location of stimulation within the physiologically defined STN has not been confirmed. We reviewed the locations of active electrical contacts in 33 patients who underwent simultaneous bilateral STN deep brain stimulator (DBS) implantation.
The location of the microelectrode-defined dorsal STN border was compared to the location of the center of the active contact(s) employed in achieving optimal clinical results 6 to 18 months postoperatively. Furthermore, the location of this optimal contact was determined with respect to each individual patient's midcommissural point. Bilateral monopolar stimulation was employed in 30 patients using quadripolar DBS electrodes.
After a minimum follow-up period of 6 months, the motor subscores (UPDRS Part III) in the postoperative on-stimulation/off-medication state were 64 ± 18% (mean ± SD) improved as compared to the preoperative off-medication state (p < 0.01). Additionally, an improvement of 53 ± 38% was noted when comparing the postoperative on-stimulation/on-medication state to the preoperative on-medication state (p < 0.01). On average, the center of the optimal contact was 13.3 mm lateral, 0.5 mm posterior, 0.1 mm inferior to the mid-commissural point and was 0.1 ± 2.1 mm dorsal to the physiologically defined dorsal STN border.
While the achieved clinical results are comparable to those published in the literature, it appears that monopolar electrical stimulation at the anterior dorsolateral border of the STN yields optimal clinical results. Further studies are crucial in determining the precise mechanism of various modes of DBS in an effort to maximize clinical outcome.

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Functional neurosurgeryEffect of bilateral subthalamic electrical stimulation in Parkinson’s disease

Abstract

Section snippets

Patients

Results

Discussion

Conclusions

Neuroscience

Trends Neurosci

Neuroscience

Subthalamotomy in treatment of Parkinson tremor

J Neurosurg

Neurophysiological effects of stimulation through electrodes in the human subthalamic nucleus

Brain

Bilateral subthalamic stimulation for Parkinson’s disease by using three-dimensional stereotactic magnetic resonance imaging and electrophysiological guidance

J Neurosurg

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

Mov Disord

Acute and long-term effects of subthalamic nucleous stimulation in Parkinson’s disease

Stereotact Funct Neurosurg

Implication of the subthalamic nucleus in the pathophysiology and pathogenesis of Parkinson’s disease

Cell Transplant

Functional neurosurgery
Effect of bilateral subthalamic electrical stimulation in Parkinson’s disease