Brain, Vol. 125, No. 3, 575-583,
March 2002
© 2002 Guarantors of Brain
Clinical predictive factors of subthalamic stimulation in Parkinson’s disease
1 Centre d’Investigation Clinique and INSERM U 289 2 Service de Biostatistique, 3 INSERM EPI 07, 4 Service d’Explorations Fonctionnelles Neurologiques, 5 Service de Neuroradiologie and 6 Service de Neurochirurgie, Hôpital de la Salpêtrière, Paris, France
Correspondence to: Dr Y. Agid, Centre d’Investigation Clinique, Hôpital de la Salpêtrière, 47 boulevard de l’Hôpital, 75013 Paris, France E-mail: agid{at}ccr.jussieu.fr
Received April 12, 2001. Revised September 9, 2001. Second revision October 15, 2001. Accepted October 22, 2001.
 |
Summary |
|---|
 Top Summary IntroductionPatients and methodsResultsDiscussionReferences |
|---|
High-frequency stimulation of the subthalamic nucleus (STN) constitutes one of the most effective treatments for advanced forms of Parkinson’s disease. The cost and potential risks of this procedure encourage the determination of clinical characteristics of patients that will have the best postoperative outcome. Forty-one Parkinson’s disease patients underwent surgery for bilateral STN stimulation. The selection criteria were severe parkinsonian motor disability, clear response of symptoms to levodopa, occurrence of disabling levodopa-related motor complications and the absence of dementia and significant abnormalities on brain MRI. Clinical evaluation was performed 1 month before and 6 months after surgery. The improvement in the activities of daily living subscale of the Unified Parkinson’s Disease Rating Scale, Part II (UPDRS II) and parkinsonian motor disability (UPDRS III) was greater when the preoperative scores for activities of daily living and parkinsonian motor disability, in particular axial symptoms, such as gait disorders and postural instability assessed at the time of maximal clinical improvement (on drug), were lower. Age and disease duration were not predictive, but parkinsonian motor disability tended to be more improved in patients with younger age and shorter disease duration. The severity of levodopa-related motor complications was not a predictive factor. The outcome of STN stimulation was excellent in levodopa-responsive forms of Parkinson’s disease, i.e. in patients with selective brain dopaminergic lesions, and moderate in patients with axial motor symptoms and cognitive impairment known to be less responsive or unresponsive to levodopa treatment, i.e. when brain non-dopaminergic lesions develop in addition to the degeneration of the nigrostriatal dopaminergic system. The results are consistent with the classical inclusion criteria for STN stimulation, but imply that the decision to operate on the oldest patients and/or patients with gait and postural disorders, who are poorly responsive to levodopa, should be weighed carefully.
Keywords: Parkinson’s disease; high-frequency stimulation; subthalamic nucleus; predictive factors
Abbreviations: ADL = activities of daily living; MADRS = Montgomery–Åsberg Depression Rating Scale; STN = subthalamic nucleus; UPDRS = Unified Parkinson’s Disease Rating Scale
|
Introduction |
|---|
|
TopSummaryIntroductionPatients and methodsResultsDiscussionReferences |
|---|
Although substitutive treatment with levodopa and dopaminergic agonists remains the most effective treatment for Parkinson’s disease (Lang and Lozano, 1998
), long-term clinical benefit for patients is fraught with disabling adverse reactions, including motor and psychic complications. Continuous bilateral high-frequency stimulation of the subthalamic nucleus (STN) is an increasingly popular neurosurgical technique that decreases the severity of parkinsonian motor disability and levodopa-induced motor complications by 60–80% and the daily dose of levodopa required by 40–80% (Limousin et al., 1998; Moro et al., 1999; Houeto et al., 2000; Molinuevo et al., 2000). Bilateral high-frequency STN stimulation is effective in Parkinson’s disease patients with a levodopa-responsive form of the disease who have disabling on–off phenomena and levodopa-induced dyskinesia in the absence of contraindications (dementia, psychiatric disorders, abnormal brain MRI) (Lang, 2000). However, the inclusion criteria that are used for STN stimulation remain imprecise. In particular, the influences of age and duration of the disease (Krack et al., 1998a) and the contributions of the various parkinsonian symptoms (Limousin et al., 1998; Bejjani et al., 2000a) have not been evaluated precisely. This study was undertaken to identify which preoperative clinical variables were predictive of the best postoperative clinical improvement in Parkinson’s disease patients treated by bilateral STN stimulation. |
Patients and methods |
|---|
|
TopSummaryIntroductionPatients and methodsResultsDiscussionReferences |
|---|
Patients
We studied 41 Parkinson’s disease patients (26 men and 15 women) who underwent surgery for the bilateral placement of stimulating electrodes within the STN between January 1996 and February 2000. The inclusion criteria for surgery were as follows: (i) age under 70 years at the time of surgery (mean age 56.4 ± 8.6 years), except for two women aged 71 and 74 years; (ii) advanced form of the disease [mean Hoehn and Yahr ‘off’ score (Hoehn and Yahr, 1967
) 4.3 ± 0.8] with a disease duration <25 years (mean 16 ± 5 years); (iii) >40% response of motor symptoms to levodopa treatment (mean improvement 72 ± 15%); (iv) occurrence of severe levodopa-related motor complications despite optimal adjustment of antiparkinsonian medication (mean daily dose of levodopa equivalent 1459 ± 600 mg/day) (Lozano et al., 1995); (v) absence of severe cognitive impairment [mean Mattis Dementia Rating Scale (Mattis, 1988) 137 ± 9, mean ‘frontal’ score (Pillon et al., 2000) 40.7 ± 10.7]; (vi) absence of depression [assessed in only 36 patients: mean Montgomery–Åsberg Depression Rating Scale (MADRS) (Montgomery and Åsberg, 1979) 10 ± 6]; and (vii) absence of corticosubcortical lesions such as severe atrophy, leucoencephalopathy and multiple lacunae on brain MRI. All patients gave informed written consent according to the Declaration of Helsinki and the protocol was approved by the local ethical committee of the Groupe Hospitalier Pitié-Salpêtrière.
Neurosurgical procedure
The neurosurgical procedure was performed as described previously (Bejjani et al., 2000b). The electrodes were implanted under local anaesthesia during a single operative session, using a combined approach of intraoperative recording and stimulation. The definitive quadripolar electrodes (model 3389-28; Medtronic, Minneapolis, Minn., USA) were implanted bilaterally and connected to a subcutaneous programmable pulse generator (Itrel II, n = 37; Kinetra, n = 4; Medtronic) in the subclavicular area. Electrical parameters (pulse width, frequency and voltage) were adjusted progressively using an electromagnetic programmer (7532 neurological programmer; Medtronic).
Clinical evaluation
Evaluation of patients was performed 1 month before and 6 months after surgery. Activities of daily living [ADL; Unified Parkinson’s Disease Rating Scale (UPDRS) Part II] (Fahn et al., 1987) were scored during an interview evaluating the state of patients in the ‘off’ and ‘on’ drug conditions. The percentage improvement in ADL was determined in respect of the preoperative ADL ‘off’ drug condition. Before surgery, evaluation of the motor disability score (UPDRS Part III) (Fahn et al., 1987) was performed in the ‘off’ state as defined by the Core Assessment Program for Surgical Interventional Therapy (CAPIT) in Parkinson’s disease (Langston et al., 1992), i.e. after an interruption of at least 12 h in antiparkinsonian medication, and in the best ‘on’ drug condition (‘residual’ motor disability score) after the administration of a single suprathreshold dose of levodopa (50 mg higher than the usual effective dose taken in the morning). The ‘axial’ score was defined as the sum of the following motor subscores: speech, gait, posture, postural stability (items 18, 28, 29 and 30 of the UPDRS Part III). The axial score was assessed in the same ‘off’ and ‘on’ drug conditions. After surgery, the parkinsonian motor disability score (UPDRS Part III) was evaluated in four conditions: (i) ‘off’ stimulation and ‘off’ drug after a night without drug treatment and after stimulation had been switched off for 12 h (first 27 patients) or for at least 1.5 h (14 patients); (ii) ‘on’ stimulation and ‘off’ drug, after stimulation had been switched on for at least 1 h; (iii) ‘off’ stimulation and ‘on’ drug after stimulation had been switched off for at least 1 h and after the administration of a suprathreshold dose of levodopa (equivalent to the preoperative dose); (iv) ‘on’ stimulation and ‘on’ drug after stimulation had been switched on using the chronic stimulation parameters. For each condition, evaluation was performed the same day and in the same order in all patients. The percentage improvement in motor disability was determined in respect of the preoperative ‘off’ drug condition. Levodopa-related complications were evaluated using the UPDRS Part IV (Fahn et al., 1987), including the duration of motor fluctuations (item 39) and levodopa-induced dyskinesias (item 32).
Statistical analysis
The effects of continuous bilateral STN stimulation on parkinsonian symptoms were evaluated using a paired Student’s t-test to compare scores obtained before and after surgery. To determine the effects of age and disease duration on the postoperative clinical outcome, we chose the mean age and mean disease duration as cut-off points for the population and we assessed the postoperative clinical improvement using a non-parametric test, the Mann–Whitney test. To determine which preoperative clinical characteristics (age, disease duration, neuropsychological evaluation, ADL and motor disability and axial scores) were predictive of the clinical outcome after surgery, we first performed a univariate analysis Pearson correlation test with a threshold of 0.0023 to prevent false positive results (Bonferroni correction). Variables relating to improvement after surgery were included in stepwise multiple linear regression with the same threshold. Statistical analysis was performed with the SAS statistical software package, version 6.12 (SAS Institute, Cary, NC, USA).
|
Results |
|---|
|
TopSummaryIntroductionPatients and methodsResultsDiscussionReferences |
|---|
Effects of continuous bilateral stimulation of the STN on parkinsonian motor disability (Table 1)
Before surgery, antiparkinsonian drug treatment improved the ADL score (UPDRS II) by 66%. Six months after surgery, the ADL score was improved by 61% when patients were under continuous STN stimulation without drug treatment (‘on’ stimulation, ‘off’ drug). The combination of STN stimulation and levodopa treatment (‘on’ stimulation, ‘on’ drug) induced a greater improvement in the ADL score (+77%) than that obtained preoperatively with the medical treatment (Table 1). Before surgery, there was a 72% improvement in parkinsonian motor disability (UPDRS III) at the time of maximal clinical improvement following the administration of levodopa. Six months after surgery, the motor disability score was improved by 64% following the administration of levodopa alone (‘off’ stimulation, ‘on’ drug condition) and by 65% under STN stimulation alone (‘on’ stimulation, ‘off’ drug condition). The combination of STN stimulation with levodopa administration induced a greater motor improvement (+80%) than that obtained with levodopa alone, either preoperatively or postoperatively, or with stimulation alone. Before surgery, there was a 68% levodopa-induced improvement in the axial motor score. After surgery, the axial score was improved by 73% when the patient was in the ‘off’ stimulation, ‘on’ drug condition. The combination of STN stimulation and levodopa administration induced a greater improvement of the axial score (+83%). Following STN stimulation, the levodopa-equivalent doses were decreased by 68%, whereas the scores for the duration of motor fluctuations, levodopa-induced dyskinesias and UPDRS IV were improved by 87, 69 and 78%, respectively.
|
Predictive factors for bilateral subthalamic stimulation: correlation between the characteristics of patients before and after surgery
Influence of age and disease duration on parkinsonian motor disability and ADL evaluated after surgery
No significant correlation was found between age at the time of surgery or disease duration and the postoperative clinical outcome (univariate analysis and multiple stepwise regression), although there was a tendency for statistical significance for some parameters [motor disability score in the ‘on’ stimulation, ‘on’ drug condition and age or disease duration (P < 0.005 and P < 0.007, respectively)] (results not shown). This led us to separate patients aged
56 years from those aged <56 years at the time of neurosurgery. Six months after surgery, the postoperative residual ADL (‘on’ stimulation, ‘off’ drug), motor disability (‘on’ stimulation, ‘on’ drug) and axial scores (‘on’ stimulation, ‘off’ drug) were lower (Table 2) and the percentage improvements in ADL (‘on’ stimulation, ‘off’ drug) and motor disability (‘on’ stimulation, ‘off’ and ‘on’ drug) scores were greater in young patients (Table 2). When patients were distinguished according to disease duration 16 versus <16 years, we found the postoperative residual ADL, motor disability and axial scores (‘on’ stimulation, ‘on’ drug) to be significantly lower (Table 2) and the percentage improvement in ADL and motor disability (‘on’ stimulation, ‘on’ drug) scores to be significantly greater in patients with shorter disease durations (Table 2).
|
Influence of patients’ preoperative clinical characteristics on ADL evaluated after surgery
There was no correlation between either the residual ADL score or the percentage improvement in ADL score (‘on’ stimulation, ‘off’ and ‘on’ drug) assessed after surgery and the following parameters evaluated before surgery: ADL score, percentage improvement in ADL score, severity of levodopa-related complications (UPDRS IV, duration of levodopa-induced dyskinesias and motor fluctuations) (not shown), the Mattis and MADRS scores and the levodopa-equivalent doses (Table 3). The residual ADL scores (‘on’ stimulation) assessed after surgery were positively correlated with the preoperative residual motor disability and axial scores (‘on’ drug) and negatively correlated with the ‘frontal’ score (Table 3). The percentage improvement in the ADL score under STN stimulation alone (‘on’ stimulation, ‘off’ drug) was negatively correlated with the levodopa-equivalent doses (Table 3). The percentage improvement in the ADL score under the combination of STN stimulation with drug treatment (‘on’ stimulation, ‘on’ drug) was negatively correlated with the preoperative residual motor disability score (‘on’ drug) (Table 3), the preoperative percentage improvement in motor disability score (not shown) and the preoperative levodopa-equivalent doses (Table 3).
|
Influence of patients’ preoperative clinical characteristics on parkinsonian motor disability evaluated after surgery
There was no correlation between either postoperative motor disability scores (UPDRS III) (‘off’ stimulation, ‘off’ drug and ‘on’ stimulation, ‘off’ drug) or the percentage improvement in motor disability (‘on’ stimulation, ‘off’ and ‘on’ drug) and the following parameters evaluated before surgery: levodopa-related complications (UPDRS IV; not shown), MADRS score and levodopa-equivalent doses (Table 3).
The postoperative residual motor disability score under STN stimulation alone (‘on’ stimulation, ‘off’ drug) was positively correlated with the ‘off’ drug motor disability score (UPDRS III) and the residual motor disability and axial scores (‘on’ drug) assessed before surgery. The postoperative residual motor disability score under both STN stimulation and drug treatment (‘on’ stimulation, ‘on’ drug) was positively correlated with the preoperative residual ADL, motor disability, axial, posture, gait and postural stability scores (‘on’ drug), and negatively correlated with the Mattis and frontal scores.
No correlation was found between the percentage improvement in motor disability score under STN stimulation alone (‘on’ stimulation, ‘off’ drug) and the preoperative clinical characteristics. The percentage improvement in motor disability under the combination of STN stimulation with drug treatment (‘on’ stimulation, ‘on’ drug) was negatively correlated with the preoperative residual ADL, motor disability, axial, posture, gait and postural stability scores (‘on’ drug) and positively correlated with the frontal score (Table 3).
In summary, the lower the parkinsonian motor disability during the best ‘on’ period (in particular gait disorders) and the higher the neuropsychological status (in particular frontal aptitudes) were before surgery, the greater the improvement in parkinsonian motor disability after surgery. In other words, the efficacy of STN stimulation on parkinsonian motor disability was dependent upon the ability of levodopa treatment to improve parkinsonian motor disability and axial symptoms before surgery.
Influence of patients’ preoperative clinical characteristics on parkinsonian axial motor symptoms evaluated after surgery
There was no correlation between either the postoperative axial motor scores (‘off’ and ‘on’ stimulation) or percentage improvement in axial symptoms under STN stimulation (‘on’ stimulation, ‘off’ and ‘on’ drug), and levodopa-related complications before surgery (not shown), MADRS, Mattis and frontal scores and the levodopa-equivalent doses before surgery (Table 3).
The postoperative residual axial score under STN stimulation alone (‘on’ stimulation, ‘off’ drug) was positively correlated with the preoperative residual ADL, motor disability, axial, posture, gait and postural stability scores (‘on’ drug). The postoperative residual axial score under the combination of STN stimulation with drug treatment (‘on’ stimulation, ‘on’ drug) was positively correlated with the same preoperative scores (Table 3).
The percentage improvement in the axial motor score under STN stimulation alone (‘on’ stimulation, ‘off’ drug) was negatively correlated with the preoperative residual axial and postural stability scores (‘on’ drug). The percentage improvement in the axial score under STN stimulation and drug treatment (‘on’ stimulation, ‘on’ drug) was negatively correlated with the preoperative residual ADL, axial, gait and postural stability scores (‘on’ drug) (Table 3).
In summary, the less severe the axial motor symptoms assessed under levodopa treatment before surgery (in particular gait disorders and postural instability), the greater the improvement in axial motor disability after surgery. In others words, the efficacy of STN stimulation on axial motor symptoms can be predicted from the assessment of axial motor symptoms during the best ‘on’ period before surgery.
Influence of patients’ preoperative clinical characteristics on levodopa-related complications and levodopa treatment evaluated after surgery
There was no correlation between the severity of levodopa-related complications (motor fluctuations, levodopa-induced dyskinesias, UPDRS IV) or levodopa-equivalent doses after surgery, and ADL score, levodopa-related complications (not shown), residual axial scores, neuropsychological status and the MADRS score before surgery (Table 4).
|
The duration of motor fluctuations after surgery was positively correlated with the ‘off’ drug motor disability score before surgery. The percentage improvement in the duration of motor fluctuations was negatively correlated with the ‘off’ drug motor disability score before surgery.
The levodopa-equivalent doses after surgery were positively correlated with the levodopa-equivalent doses before surgery.
In summary, the efficacy of STN stimulation on levodopa-related complications was independent of the severity and duration of these motor complications evaluated before surgery.
|
Discussion |
|---|
|
TopSummaryIntroductionPatients and methodsResultsDiscussionReferences |
|---|
This study was undertaken to try to define predictive factors for the outcome of treatment for Parkinson’s disease by continuous bilateral stimulation of the STN. In this group of 41 patients, who were rigorously selected on classical but empirical criteria (see Patients and methods), we found that the outcome of neurosurgery was influenced partly by the age of the patients and the duration of the disease and was markedly dependent upon whether the parkinsonian motor symptoms responded to levodopa treatment. The severity of axial motor symptoms evaluated at the time of maximal clinical improvement under levodopa treatment (‘on’ drug), in particular the levels of gait disorders and postural instability, was a highly effective predictive factor, whereas the severity of levodopa-induced complications was not.
Influence of age and duration of the disease
Age tended to be significantly correlated with the effectiveness of STN stimulation (P < 0.005, Pearson correlation test) and older patients were less improved than younger patients (Table 2), which is in agreement with a previous report (Kumar et al., 1998). The conjunction of a lesser improvement after surgery with a higher risk of postoperative complications (Kumar et al., 1998; Saint-Cyr and Trepanier, 2000) and social maladjustment suggests that the decision to operate in such patients should be weighed carefully. There was also a tendency for patients with a longer disease duration to be less improved by surgery (P < 0.007, Pearson correlation test) (Table 2), suggesting that STN stimulation might be envisaged at an earlier stage of the disease. However, whether this might be worthwhile remains to be confirmed prospectively.
The reason why the efficacy of STN stimulation seems to diminish with patient age and disease duration is unknown. Assuming that the clinical benefit induced by STN stimulation is similar to that observed with levodopa treatment (Pollak et al., 1996; Pinter et al., 1999a, b), the mechanism responsible for it may be similar to the mechanism underlying the effect of levodopa treatment, which is also known to lose efficacy progressively with age (Blin et al., 1991) and disease duration (Bonnet et al., 1987).
Influence of the characteristics of parkinsonian motor symptoms and levodopa treatment
The efficacy of neurosurgery was not dependent upon the severity of parkinsonian motor disability, assessed preoperatively in the absence of levodopa treatment (‘off’ drug) (Table 4). The best predictive factors were a good response to levodopa, in particular when the residual motor disability score (especially gait disorders and postural instability) was low (‘on’ drug) (Tables 3 and 4). This confirms that bilateral STN stimulation in Parkinson’s disease patients who are good responders to levodopa results in motor improvement mimicking the effects produced by levodopa (Pollak et al., 1996; Krack et al., 1998b; Pinter et al., 1999). Bilateral stimulation of the STN, therefore, seems to have the same effects downstream from the lesions of the dopaminergic nigrostriatal system as the re-establishment of normal dopaminergic transmission in the striatum of patients. The fact that the severity of the residual parkinsonian motor score in the ‘on’ drug condition and, especially, the axial motor score (known to be less responsive to levodopa treatment) were predictive of a poor postoperative outcome is probably explained by the presence of non-dopaminergic lesions within the basal ganglia, in addition to the characteristic degeneration of the dopaminergic nigrostriatal pathway (Agid, 1991). In line with this suggestion is the relative failure of STN stimulation in the treatment of other parkinsonian syndromes, such as multiple system atrophy (Pinter et al., 1999) and vascular parkinsonism (Krack et al., 2000), which are characterized by the presence of additional non-dopaminergic lesions in the brain. Taken together, these results stress the importance of the levodopa test, performed before surgery, for the accurate evaluation of the levodopa-responsive motor score (difference between the ‘off’ drug and ‘on’ drug parkinsonian motor scores), which reflects the severity of the degeneration of the nigrostriatal system, and the residual motor score (‘on’ drug), which reflects the severity of the non-dopaminergic lesions. Our data provide firm evidence in favour of excluding from neurosurgery patients with axial motor symptoms that respond poorly or not at all to levodopa, in particular gait disorders and postural instability, the severities of which are known to increase during the course of the disease (Bonnet et al., 1987).
Influence of dopaminergic treatment and related motor complications on the outcome of neurosurgery
The improvement of parkinsonian symptoms by STN stimulation was not related to the severity of levodopa-induced motor complications evaluated before surgery (Table 4). This indicates that, theoretically, the decision to operate should be based on the existence, rather than the severity, of levodopa-related fluctuations in motor performance and levodopa-induced dyskinesias. The severity of these motor complications is nevertheless taken into account when deciding whether to include patients for neurosurgery, as it constitutes a major factor in disability.
Patients receiving high doses of levodopa before neurosurgery also required a high daily intake of levodopa after the operation (Table 4). It is unlikely that lack of improvement in parkinsonian motor disability can explain this observation, as motor symptoms were markedly improved by STN stimulation alone (Table 1), even when the levodopa treatment was reduced (not shown). The high doses of levodopa still being taken by some patients postoperatively, despite motor improvement, might have contributed to the persistence of adverse motor reactions, causing persistent impairment in ADL (Table 3).
Conclusion
Our results confirm the efficacy of continuous bilateral high-frequency stimulation of the STN in a levodopa-responsive form of Parkinson’s disease and suggest that age, long disease duration and residual axial motor symptoms that have a low level of responsiveness to levodopa treatment, in particular gait disorders and postural instability, are factors contributing to an unfavourable motor outcome of neurosurgery. Other factors may contribute to the outcome of neurosurgery, and the issue of quality of life, which was not evaluated in the present study, remains to be addressed.
|
Acknowledgements |
|---|
We wish to thank the nurses of the Centre d’Investigation Clinique for providing care for the patients. The study was supported by INSERM and the National Parkinson Foundation-Miami.
|
References |
|---|
|
TopSummaryIntroductionPatients and methodsResultsDiscussionReferences |
|---|
Agid Y. Parkinson’s disease: pathophysiology. [Review]. Lancet 1991; 337: 1321–4.[Web of Science][Medline]
Bejjani BP, Gervais D, Arnulf I, Papadopoulos S, Demeret S, Bonnet AM, et al. Axial parkinsonian symptoms can be improved: the role of levodopa and bilateral subthalamic stimulation. J Neurol Neurosurg Psychiatry 2000a; 68: 595–600.
Bejjani BP, Dormont D, Pidoux B, Yelnik J, Damier P, Arnulf I, et al. Bilateral subthalamic stimulation for Parkinson’s disease by using three-dimensional stereotactic magnetic resonance imaging and electrophysiological guidance. J Neurosurg 2000b; 92: 615–25.[Web of Science][Medline]
Blin J, Dubois B, Bonnet AM, Vidailhet M, Brandabur M, Agid Y. Does ageing aggravate parkinsonian disability? J Neurol Neurosurg Psychiatry 1991; 54: 780–2.
Bonnet AM, Loria Y, Saint-Hilaire MH, Lhermitte F, Agid Y. Does long-term aggravation of Parkinson’s disease result from nondopaminergic lesions? Neurology 1987; 37: 1539–42.
Fahn S, Elton R and Members of UPDRS Development Committee. Unified Parkinson’s disease rating scale. In: Fahn S, Marsden C, Calne D, Goldstein M, editors. Recent developments in Parkinson’s disease, Vol. 2. New York: Macmillan; 1987. p. 153–63.
Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1967; 17: 427–42.
Houeto JL, Damier P, Bejjani PB, Staedler C, Bonnet AM, Arnulf I, et al. Subthalamic stimulation in Parkinson disease: a multidisciplinary approach. Arch Neurol 2000; 57: 461–5.
Krack P, Pollak P, Limousin P, Hoffmann D, Xie J, Benazzouz A, et al. Subthalamic nucleus or internal pallidal stimulation in young onset Parkinson’s disease. Brain 1998a; 121: 451–7.
Krack P, Limousin P, Pollak P, Benazzouz A, Koudsie A, Benabid AL. The preoperative response to an acute L-dopa-test predicts the out-come of subthalamic nucleus stimulation in Parkinson’s disease [abstract]. Mov Disord 1998b; 13 Suppl 2: 296.
Krack P, Dowsey PL, Benabid AL, Acarin N, Benazzouz A, Kunig G, et al. Ineffective subthalamic nucleus stimulation in levodopa-resistant postischemic parkinsonism. Neurology 2000; 54: 2182–4.
Kumar R, Lozano A M, Kim YJ, Hutchison WD, Sime E, Halket E, et al. Double-blind evaluation of subthalamic nucleus deep brain stimulation in advanced Parkinson’s disease. Neurology 1998; 51: 850–5.
Lang AE. Surgery for Parkinson’s disease: a critical evaluation of the state of the art. [Review]. Arch Neurol 2000; 57: 1118–25.
Lang AE, Lozano AM. Parkinson’s disease. Second of two parts. New Engl J Med 1998; 339: 1130–43.
Langston JW, Widner H, Goetz CG, Brooks D, Fahn S, Freeman T, et al. Core assessment program for intracerebral transplantations (CAPIT). Mov Disord 1992; 7: 2–13.[Web of Science][Medline]
Limousin P, Krack P, Pollak P, Benazzouz A, Ardouin C, Hoffmann D, et al. Electrical stimulation of the subthalamic nucleus in advanced Parkinson’s disease. New Engl J Med 1998; 339: 1105–11.
Lozano AM, Lang AE, Galvez-Jimenez N, Miyasaki J, Duff J, Hutchinson WD, et al. Effect of GPi pallidotomy on motor function in Parkinson’s disease. Lancet 1995; 346: 1383–7.[Web of Science][Medline]
Mattis S. Dementia Rating Scale. Odessa (FL): Psychological Assessment Resources; 1988.
Molinuevo JL, Valldeoriola F, Tolosa E, Rumia J, Valls-Sole J, Roldan H, et al. Levodopa withdrawal after bilateral subthalamic nucleus stimulation in advanced Parkinson disease. Arch Neurol 2000; 57: 983–8.
Montgomery SA, Åsberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979; 134: 382–9.
Moro E, Scerrati M, Romito LM, Roselli R, Tonali P, Albanese A. Chronic subthalamic nucleus stimulation reduces medication requirements in Parkinson’s disease. Neurology 1999; 53: 85–90.
Pillon B, Ardouin C, Damier P, Krack P, Houeto JL, Klinger H, et al. Neuropsychological changes between ‘off’ and ‘on’ STN or GPi stimulation in Parkinson’s disease. Neurology 2000; 55: 411–18.
Pinter MM, Alesch F, Murg M, Helscher RJ, Binder H. Apomorphine test: a predictor for motor responsiveness to deep brain stimulation of the subthalamic nucleus. J Neurol 1999; 246: 907–13.[Web of Science][Medline]
Pollak P, Benabid AL, Limousin P, Benazzouz A, Hoffmann D, Le Bas JF, et al. Subthalamic nucleus stimulation alleviates akinesia and rigidity in parkinsonian patients. Adv Neurol 1996; 69: 591–4.[Web of Science][Medline]
Saint-Cyr JA, Trepanier LL. Neuropsychologic assessment of patients for movement disorder surgery. [Review]. Mov Disord 2000; 15: 771–83.[Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S.J. Groiss, L. Wojtecki, M. Sudmeyer, and A. Schnitzler Review: Deep brain stimulation in Parkinson's disease Therapeutic Advances in Neurological Disorders, November 1, 2009; 2(6): 379 - 391. [Abstract] [PDF]
|
|
|
|
 |
|
 M. J. Lehmkuhle, S. S. Bhangoo, and D. R. Kipke The Electrocorticogram Signal Can Be Modulated With Deep Brain Stimulation of the Subthalamic Nucleus in the Hemiparkinsonian Rat J Neurophysiol, September 1, 2009; 102(3): 1811 - 1820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. M. Poon and M. G. Irwin Anaesthesia for deep brain stimulation and in patients with implanted neurostimulator devices Br. J. Anaesth., August 1, 2009; 103(2): 152 - 165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Chastan, G. W. M. Westby, J. Yelnik, E. Bardinet, M. C. Do, Y. Agid, and M. L. Welter Effects of nigral stimulation on locomotion and postural stability in patients with Parkinson's disease Brain, January 1, 2009; 132(1): 172 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Kuhn, F. Kempf, C. Brucke, L. Gaynor Doyle, I. Martinez-Torres, A. Pogosyan, T. Trottenberg, A. Kupsch, G.-H. Schneider, M. I. Hariz, et al. High-Frequency Stimulation of the Subthalamic Nucleus Suppresses Oscillatory {beta} Activity in Patients with Parkinson's Disease in Parallel with Improvement in Motor Performance J. Neurosci., June 11, 2008; 28(24): 6165 - 6173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Le Jeune, J. Peron, I. Biseul, S. Fournier, P. Sauleau, S. Drapier, C. Haegelen, D. Drapier, B. Millet, E. Garin, et al. Subthalamic nucleus stimulation affects orbitofrontal cortex in facial emotion recognition: a pet study Brain, June 1, 2008; 131(6): 1599 - 1608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Anheim, A. Batir, V. Fraix, M. Silem, S. Chabardes, E. Seigneuret, P. Krack, A.-L. Benabid, and P. Pollak Improvement in Parkinson Disease by Subthalamic Nucleus Stimulation Based on Electrode Placement: Effects of Reimplantation Arch Neurol, May 1, 2008; 65(5): 612 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. U. Ferraye, B. Debu, V. Fraix, J. Xie-Brustolin, S. Chabardes, P. Krack, A-L Benabid, and P. Pollak Effects of subthalamic nucleus stimulation and levodopa on freezing of gait in Parkinson disease Neurology, April 15, 2008; 70(16_Part_2): 1431 - 1437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Ahlskog Beating a dead horse: Dopamine and Parkinson disease Neurology, October 23, 2007; 69(17): 1701 - 1711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. -P. Derost, L. Ouchchane, D. Morand, M. Ulla, P. -M. Llorca, M. Barget, B. Debilly, J. -J. Lemaire, and F. Durif Is DBS-STN appropriate to treat severe Parkinson disease in an elderly population? Neurology, April 24, 2007; 68(17): 1345 - 1355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.M.M. Schupbach, D. Maltete, J. L. Houeto, S. T. du Montcel, L. Mallet, M. L. Welter, M. Gargiulo, C. Behar, A. M. Bonnet, V. Czernecki, et al. Neurosurgery at an earlier stage of Parkinson disease: A randomized, controlled trial Neurology, January 23, 2007; 68(4): 267 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-L. Houeto, L. Mallet, V. Mesnage, S. Tezenas du Montcel, C. Behar, M. Gargiulo, F. Torny, A. Pelissolo, M.-L. Welter, and Y. Agid Subthalamic Stimulation in Parkinson Disease: Behavior and Social Adaptation. Arch Neurol, August 1, 2006; 63(8): 1090 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Schupbach, M. Gargiulo, M. L. Welter, L. Mallet, C. Behar, J. L. Houeto, D. Maltete, V. Mesnage, and Y. Agid Neurosurgery in Parkinson disease: A distressed mind in a repaired body? Neurology, June 27, 2006; 66(12): 1811 - 1816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Pahwa, S. A. Factor, K. E. Lyons, W. G. Ondo, G. Gronseth, H. Bronte-Stewart, M. Hallett, J. Miyasaki, J. Stevens, and W. J. Weiner Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, April 11, 2006; 66(7): 983 - 995. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V Fraix, J-L Houeto, C Lagrange, C Le Pen, P Krystkowiak, D Guehl, C Ardouin, M-L Welter, F Maurel, L Defebvre, et al. Clinical and economic results of bilateral subthalamic nucleus stimulation in Parkinson's disease J. Neurol. Neurosurg. Psychiatry, April 1, 2006; 77(4): 443 - 449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W M M Schupbach, N Chastan, M L Welter, J L Houeto, V Mesnage, A M Bonnet, V Czernecki, D Maltete, A Hartmann, L Mallet, et al. Stimulation of the subthalamic nucleus in Parkinson's disease: a 5 year follow up J. Neurol. Neurosurg. Psychiatry, December 1, 2005; 76(12): 1640 - 1644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Rodriguez-Oroz, J. A. Obeso, A. E. Lang, J.-L. Houeto, P. Pollak, S. Rehncrona, J. Kulisevsky, A. Albanese, J. Volkmann, M. I. Hariz, et al. Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up Brain, October 1, 2005; 128(10): 2240 - 2249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Capecci, R A Ricciuti, D Burini, V G Bombace, L Provinciali, M Iacoangeli, M Scerrati, and M G Ceravolo Functional improvement after subthalamic stimulation in Parkinson's disease: a non-equivalent controlled study with 12-24 month follow up J. Neurol. Neurosurg. Psychiatry, June 1, 2005; 76(6): 769 - 774. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V Czernecki, B Pillon, J L Houeto, M L Welter, V Mesnage, Y Agid, and B Dubois Does bilateral stimulation of the subthalamic nucleus aggravate apathy in Parkinson's disease? J. Neurol. Neurosurg. Psychiatry, June 1, 2005; 76(6): 775 - 779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Colnat-Coulbois, G C Gauchard, L Maillard, G Barroche, H Vespignani, J Auque, and P. P Perrin Bilateral subthalamic nucleus stimulation improves balance control in Parkinson's disease J. Neurol. Neurosurg. Psychiatry, June 1, 2005; 76(6): 780 - 787. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Samuel and V Voon Beyond the holy grail of motor symptoms: deep brain stimulation for Parkinson's disease J. Neurol. Neurosurg. Psychiatry, June 1, 2005; 76(6): 759 - 760. [Full Text] [PDF]
|
|
|
|
|
|
F. Bonneville, M. L. Welter, C. Elie, S. T. du Montcel, D. Hasboun, C. Menuel, J. L. Houeto, A. M. Bonnet, V. Mesnage, B. Pidoux, et al. Parkinson disease, brain volumes, and subthalamic nucleus stimulation Neurology, May 10, 2005; 64(9): 1598 - 1604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. C. Anderson, K. J. Burchiel, P. Hogarth, J. Favre, and J. P. Hammerstad Pallidal vs Subthalamic Nucleus Deep Brain Stimulation in Parkinson Disease Arch Neurol, April 1, 2005; 62(4): 554 - 560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Russmann, J. Ghika, J.-G. Villemure, B. Robert, J. Bogousslavsky, P. R. Burkhard, and F. J.G. Vingerhoets Subthalamic nucleus deep brain stimulation in Parkinson disease patients over age 70 years Neurology, November 23, 2004; 63(10): 1952 - 1954. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B Ford, L Winfield, S L Pullman, S J Frucht, Y Du, P Greene, J H Cheringal, Q Yu, L J Cote, S Fahn, et al. Subthalamic nucleus stimulation in advanced Parkinson's disease: blinded assessments at one year follow up J. Neurol. Neurosurg. Psychiatry, September 1, 2004; 75(9): 1255 - 1259. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Maltete, S. Navarro, M.-L. Welter, S. Roche, A.-M. Bonnet, J.-L. Houeto, V. Mesnage, B. Pidoux, D. Dormont, P. Cornu, et al. Subthalamic Stimulation in Parkinson Disease: With or Without Anesthesia? Arch Neurol, March 1, 2004; 61(3): 390 - 392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K Dujardin, S Blairy, L Defebvre, P Krystkowiak, U Hess, S Blond, and A Destee Subthalamic nucleus stimulation induces deficits in decoding emotional facial expressions in Parkinson's disease J. Neurol. Neurosurg. Psychiatry, February 1, 2004; 75(2): 202 - 208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Devos, E. Labyt, P. Derambure, J. L. Bourriez, F. Cassim, N. Reyns, S. Blond, J. D. Guieu, A. Destee, and L. Defebvre Subthalamic nucleus stimulation modulates motor cortex oscillatory activity in Parkinson's disease Brain, February 1, 2004; 127(2): 408 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G Linazasoro, J L Houeto, V Mesnage, L Mallet, M L Welter, D Dormont, B Pidoux, P Cornu, and Y Agid Subthalamic deep brain stimulation for advanced Parkinson's disease: all that glitters is not gold J. Neurol. Neurosurg. Psychiatry, June 1, 2003; 74(6): 827 - 827. [Full Text] [PDF]
|
|
|
|
|
|
J.-L. Houeto, M.-L. Welter, P.-B. Bejjani, S. T. du Montcel, A.-M. Bonnet, V. Mesnage, S. Navarro, B. Pidoux, D. Dormont, P. Cornu, et al. Subthalamic Stimulation in Parkinson Disease: Intraoperative Predictive Factors Arch Neurol, May 1, 2003; 60(5): 690 - 694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. B. Montgomery Jr., P.D. Charles, N. Van Blercom, P. Krack, S.L. Lee, J. Xie, G. Besson, A.L. Benabid, and P. Pollak Predictors of effective bilateral subthalamic nucleus stimulation for PD Neurology, March 11, 2003; 60(5): 886 - 887. [Full Text] [PDF]
|
|
|
|
|
|
V Mesnage, J-L Houeto, M-L Welter, Y Agid, B Pidoux, D Dormont, and P Cornu Parkinson's disease: neurosurgery at an earlier stage? J. Neurol. Neurosurg. Psychiatry, December 1, 2002; 73(6): 778 - 778. [Full Text] [PDF]
|
|
|
|
|
|
R. Pahwa, S. A. Factor, K. E. Lyons, W. G. Ondo, G. Gronseth, H. Bronte-Stewart, M. Hallett, J. Miyasaki, J. Stevens, and W. J. Weiner Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, April 11, 2006; 66(7): 983 - 995. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||