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L. Vercueil,
J. L. Houeto,
P. Krystkowiak, C. Lagrange,
F. Cassim,
A. Benazzouz,
B. Pidoux,
A. Destée,
Y. Agid,
P. Cornu,
S. Blond,
A. L. Benabid,
P. Pollak,
M. Vidailhet,
and the Spidy GROUP (French Pallidal stimulation Group for dystonia
[show abstract]
[hide abstract]
ABSTRACT: Background
Various pulse widths (from 60–450 μs) have been used for bilateral pallidal stimulation in generalized dystonia but, to date,
no comparison of this parameter’s effects is available.
Objective
To provide an analysis of the differential effects of bilateral short, medium and long stimulus pulse width (PW) on clinical
improvement in primary generalized dystonia.
Methods
The most effective therapeutic stimulation parameters were recorded in 22 patients using bilateral pallidal stimulation. Six
months after surgery, the effects of bilateral pallidal short (60–90 μs), medium (120–150 μs) and long (450 μs) PWs were studied
in 20 of those patients. The effect of the stimulation was assessed by reviewing videotaped sessions by an observer blinded
to treatment status (Burke-Fahn-Marsden movement score). Patients were tested on separate days, in random order, for the stimulation
conditions (acute effect with the stimulation condition lasting 10 hours). The same contact was used for each stimulation
condition. All the electrodes were set at 130 Hz (monopolar stimulation) and the intensity was set individually 10% below
the side effect threshold.
Results
Median PWs of 60 (short), 120 (medium) and 450 μs (long) were compared,with a mean intensity of 4.46, 3.45 and 2.47 V, respectively.
This study failed to demonstrate any significant difference in the movementscale dystonia mean scores depending on PW.
Conclusion
According to our findings, shortduration stimulus PWs are as effective as longer ones during a 10 hour period of observation.
Confirmation of this finding for chronic use could be of importance in saving stimulator energy. Moreover, the use of smaller
stimulus pulse widths are said to reduce charge injection and increase the therapeutic window between therapeutic effects
and side effects.
Journal of Neurology 04/2012; 254(11):1533-1537. · 3.47 Impact Factor
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S Thobois,
C Ardouin,
E Schmitt,
E Lhommée,
H Klinger,
J Xie, C Lagrange,
A Kistner,
M Aya Kombo,
V Fleury,
A Poisson,
V Fraix,
E Broussolle,
P Pollak,
P Krack
[show abstract]
[hide abstract]
ABSTRACT: Behavioral changes in Parkinson's disease are complex and their pathophysiology is not yet fully understood. The dopaminergic system seems to play a major role and most of the behavioral disorders in Parkinson's disease can be classified into either hypodopaminergic if related to the disease itself or hyperdopaminergic if related to dopaminergic treatment.
Subthalamic stimulation, which enables withdrawal of dopaminergic medication at an advanced stage in the disease, provides a model for the study of certain nonmotor, dopamine-sensitive symptoms. Such a study has shown that apathy, which is the most frequent behavioral problem in Parkinson's disease, is part of a much broader hypodopaminergic behavioral syndrome which also includes anxiety and depression. Nonmotor fluctuations--essential fluctuations in the patient's psychological state--are an expression of mesolimbic denervation, as shown in positron emission tomography. Drug-induced sensitization of the denervated mesolimbic system accounts for hyperdopaminergic behavioral problems that encompass impulse control disorders that can be alternatively classified as behavioral addictions. The association of impulse control disorders and addiction to the dopaminergic medication has been called dopamine dysregulation syndrome. While L-dopa is the most effective treatment for motor symptoms, dopamine agonists are more effective in improving the nonmotor levodopa-sensitive symptoms. On the other hand, L-dopa induces more motor complications and dopamine agonist more behavioral side effects. There is increasing data and awareness that patients' quality of life appears to be dictated by hypo- and hyperdopaminergic psychological symptoms stemming from mesolimbic denervation and dopaminergic treatment rather than by motor symptoms and motor complications related to nigrostriatal denervation and dopaminergic treatment.
Better management requires knowledge of the clinical syndromes of hyper- and hypodopaminergic behaviors and nonmotor fluctuations, a better understanding of their underlying mechanisms and the development of new evaluation tools for these nonmotor symptoms.
The neurologist who strives to gain mastery of dopaminergic treatment needs to fine tune the dosage of levodopa and dopamine agonists on an individual basis, depending on the presence of motor and nonmotor signs respectively.
Revue Neurologique 10/2010; 166(10):816-21. · 0.49 Impact Factor
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V Fraix,
J-L Houeto, C Lagrange,
C Le Pen,
P Krystkowiak,
D Guehl,
C Ardouin,
M-L Welter,
F Maurel,
L Defebvre,
A Rougier,
A-L Benabid,
V Mesnage,
M Ligier,
S Blond,
P Burbaud,
B Bioulac,
A Destée,
P Cornu,
P Pollak
[show abstract]
[hide abstract]
ABSTRACT: High frequency stimulation of the subthalamic nucleus (STN) is an alternative but expensive neurosurgical treatment for parkinsonian patients with levodopa induced motor complications.
To assess the safety, clinical effects, quality of life, and economic cost of STN stimulation.
We conducted a prospective multicentre study in 95 consecutive Parkinson's disease (PD) patients receiving bilateral STN stimulation and assessed its effects over 12 months. A double blind randomised motor evaluation was carried out at 3 month follow up, and quality of life, self care ability, and predictive factors of outcome following surgery were assessed. The cost of PD was estimated over 6 months before and after surgery.
The Unified Parkinson's Disease Rating Scale (UPDRS) motor score improved by 57% (p<0.0001) and activities of daily living improved by 48% (p<0.0001) at 12 month follow up. Double blind motor scoring improved by 51% at 3 month follow up (p<0.0001). The total PD Quality of Life Questionnaire (PDQL-37) score improved by 28% (p<0.001). The better the preoperative motor score after a levodopa challenge, the better the outcome after STN stimulation. Five patients developed an intracerebral haematoma during electrode implantation with permanent after effects in two. The 6 month costs of PD decreased from 10,087 euros before surgery to 1673 euros after surgery (p<0.0001) mainly because of the decrease in medication. These savings allowed a return on the procedure investment, estimated at 36,904 euros over 2.2 years.
STN stimulation has good outcomes with relatively low risk and little cost burden in PD patients with levodopa induced motor complications.
Journal of Neurology Neurosurgery & Psychiatry 04/2006; 77(4):443-9. · 4.76 Impact Factor
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S. Thobois,
C. Ardouin,
E. Schmitt,
E. Lhommée,
H. Klinger,
J. Xie, C. Lagrange,
A. Kistner,
M. Aya Kombo,
V. Fleury,
A. Poisson,
V. Fraix,
E. Broussolle,
P. Pollak,
P. Krack
[show abstract]
[hide abstract]
ABSTRACT: IntroductionBehavioral changes in Parkinson's disease are complex and their pathophysiology is not yet fully understood. The dopaminergic system seems to play a major role and most of the behavioral disorders in Parkinson's disease can be classified into either hypodopaminergic if related to the disease itself or hyperdopaminergic if related to dopaminergic treatment.State of the artSubthalamic stimulation, which enables withdrawal of dopaminergic medication at an advanced stage in the disease, provides a model for the study of certain nonmotor, dopamine-sensitive symptoms. Such a study has shown that apathy, which is the most frequent behavioral problem in Parkinson's disease, is part of a much broader hypodopaminergic behavioral syndrome which also includes anxiety and depression. Nonmotor fluctuations – essentially fluctuations in the patient's psychological state – are an expression of mesolimbic denervation, as shown in positron emission tomography. Drug-induced sensitization of the denervated mesolimbic system accounts for hyperdopaminergic behavioral problems that encompass impulse control disorders that can be alternatively classified as behavioral addictions. The association of impulse control disorders and addiction to the dopaminergic medication has been called dopamine dysregulation syndrome. While L-dopa is the most effective treatment for motor symptoms, dopamine agonists are more effective in improving the nonmotor levodopa-sensitive symptoms. On the other hand, L-dopa induces more motor complications and dopamine agonist more behavioral side effects. There is increasing data and awareness that patients’ quality of life appears to be dictated by hypo- and hyperdopaminergic psychological symptoms stemming from mesolimbic denervation and dopaminergic treatment rather than by motor symptoms and motor complications related to nigrostriatal denervation and dopaminergic treatment.PerspectivesBetter management requires knowledge of the clinical syndromes of hyper- and hypodopaminergic behaviors and nonmotor fluctuations, a better understanding of their underlying mechanisms and the development of new evaluation tools for these nonmotor symptoms.Conclusions
The neurologist who strives to gain mastery of dopaminergic treatment needs to fine tune the dosage of levodopa and dopamine agonists on an individual basis, depending on the presence of motor and nonmotor signs respectively.
Revue Neurologique 166(10):816-821. · 0.49 Impact Factor
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J. L. Houeto,
J. Yelnik,
E. Bardinet,
L. Vercueil,
P. Krystkowiak,
V. Mesnage, C. Lagrange,
D. Dormont,
J. F. Le Bas,
J. P. Pruvo,
S. Tezenas du Moncel,
P. Pollak,
Y. Agid,
A. Destee,
M. Vidailhet
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Dystonia is a syndrome characterized by prolonged muscle contractions that cause sustained twisting movements and abnormal posturing of body parts. Patients with the severe and generalized forms can benefit from bilateral high-frequency pallidal stimulation. OBJECTIVE: To investigate the functional map of the globus pallidus (GP) in patients with primary generalized dystonia. DESIGN: Prospective multicenter, double-blind, video-controlled study in patients treated at a university hospital. SETTING: University secondary care centers. PATIENTS: Twenty-two patients with primary generalized dystonia. INTERVENTIONS: Acute internal and external pallidal deep-brain stimulation or pallidal deep-brain stimulation. MAIN OUTCOME MEASURES: The clinical effects of acute bilateral high-frequency ventral vs acute dorsal pallidal stimulation were assessed with the Movement subscale of the Burke-Fahn-Marsden Dystonia Rating Scale. Intrapallidal localization of the contacts of the quadripolar electrodes was performed using a 3-dimensional atlas-magnetic resonance imaging coregistration method by investigators blinded to the clinical outcome. RESULTS: Bilateral acute ventral stimulation of the GP significantly improved the Burke-Fahn-Marsden Dystonia Rating Scale score by 42% and resulted in stimulation of contacts located in the internal GP or medullary lamina in 18 of 21 patients. Bilateral acute dorsal pallidal stimulation, primarily localized within the external GP, had variable effects across patients, with half demonstrating slight or no improvement or even aggravation of dystonia compared with baseline. CONCLUSIONS: Ventral pallidal stimulation, primarily of the internal GP or medullary lamina or both, is the optimal method for the treatment of dystonia. The varying effects across patients of bilateral acute dorsal pallidal stimulation, primarily of the external GP, suggest that unknown factors associated with dystonia could have a role in and contribute to the effects of the electrical stimulation.
Arch Neurol. 64(9):1281-6.
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ABSTRACT: BACKGROUND: The multicenter SPIDY trial (pallidal stimulation for generalized, idiopathic dystonia) recently reported a marked improvement in dystonia which was assessed by the Burke-Fahn-Marsden (BFM) scale. However, the reliability of this tool has rarely been evaluated and its use in a multicenter study has never been assessed prospectively. PURPOSE: To evaluate the concordance between three unblinded clinical raters and one single-blinded rater for 10 prospective series of ratings on the BFM scale in 22 dystonic patients of the SPIDY study. METHODS: Ten assessments on the BFM scale were performed under various stimulation conditions at different time points (before surgery and 1, 3, 6, and 12 months afterwards). Patients were first evaluated by three unblinded clinical raters (one per center). All assessments were videotaped and sent to a blinded rater. Intra- and inter-rater reliability was assessed using intraclass correlation coefficients. RESULTS: The intra-rater reliability at inclusion was better for the blinded rater than for the clinical raters. The inter-rater reliability (comparing the blinded rater with each clinical rater) was "very good" at inclusion, "fair" at month 1 and was "good" at month 3, month 6, and month 12. CONCLUSION: Blinding (rather than video) is probably the key factor in better intra-rater reliability and can produce more accurate rating than clinical rating. Consequently, a blind procedure should be performed systematically in multicenter studies. As inter-rater reliability is good in trained unblinded raters, the BFM scale may also be used in the follow up of dystonic patients in movement disorders centers, in clinical practice.
Mov Disord. 22(5):685-9.
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M. Vidailhet,
L. Vercueil,
J. L. Houeto,
P. Krystkowiak,
A. L. Benabid,
P. Cornu, C. Lagrange,
S. Tezenas du Montcel,
D. Dormont,
S. Grand,
S. Blond,
O. Detante,
B. Pillon,
C. Ardouin,
Y. Agid,
A. Destee,
P. Pollak
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Severe forms of dystonia respond poorly to medical treatment. Deep-brain stimulation is a reversible neurosurgical procedure that has been used for the treatment of dystonia, but assessment of its efficacy has been limited to open studies. METHODS: We performed a prospective, controlled, multicenter study assessing the efficacy and safety of bilateral pallidal stimulation in 22 patients with primary generalized dystonia. The severity of dystonia was evaluated before surgery and 3, 6, and 12 months postoperatively during neurostimulation, with the use of the movement and disability subscores of the Burke-Fahn-Marsden Dystonia Scale (range, 0 to 120 and 0 to 30, respectively, with higher scores indicating greater impairment). Movement scores were assessed by a review of videotaped sessions performed by an observer who was unaware of treatment status. At three months, patients underwent a double-blind evaluation in the presence and absence of neurostimulation. We also assessed the patients' quality of life, cognition, and mood at baseline and 12 months. RESULTS: The dystonia movement score improved from a mean (+/-SD) of 46.3+/-21.3 before surgery to 21.0+/-14.1 at 12 months (P<0.001). The disability score improved from 11.6+/-5.5 before surgery to 6.5+/-4.9 at 12 months (P<0.001). General health and physical functioning were significantly improved at month 12; there were no significant changes in measures of mood and cognition. At the three-month evaluation, dystonia movement scores were significantly better with neurostimulation than without neurostimulation (24.6+/-17.7 vs. 34.6+/-12.3, P<0.001). There were five adverse events (in three patients); all resolved without permanent sequelae. CONCLUSIONS: These findings support the efficacy and safety of the use of bilateral stimulation of the internal globus pallidus in selected patients with primary generalized dystonia.
N Engl J Med. 352(5):459-67.
