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Simone Hemm, Gérard Mennessier, Nathalie Vayssiere, Laura Cif, Hassan El Fertit, and Philippe Coubes

Object. Adjusting electrical parameters used in deep brain stimulation (DBS) for dystonia remains time consuming and is currently based on clinical observation alone. The goal of this study was to visualize electrical parameters around the electrode, to correlate these parameters with the anatomy of the globus pallidus internus (GPI), and to study the relationship between the volume of stimulated tissue and the electrical parameter settings.

Methods. The authors developed a computer-assisted methodological model for visualizing electrical parameters (the isopotential and the isoelectric field magnitude), with reference to the stereotactic target, for different stimulation settings (monopolar and bipolar) applied during DBS. Electrical field values were correlated with the anatomy of the GPI, which was determined by performing stereotactic magnetic resonance imaging in one reference patient.

By using this method it is possible to compare potential and electrical field distributions for different stimulation modes. In monopolar and bipolar stimulation, the shape and distribution of the potential and electrical field are different and depend on the stimulation voltage. Distributions visualized for patient-specific parameters can be subsequently correlated with anatomical information. The application of this method to one patient demonstrated that the 0.2-V/mm isofield line fits best with the lateral GPI borders at the level of the stimulated contacts.

Conclusions. The electrical field is a crucial parameter because it is assumed to be responsible for triggering action potentials. Electrical field visualization allows the calculation of the stimulated volume for a given isoline. Its application to an entire series of patients may help determine a threshold for obtaining a therapeutic effect, which is currently unknown, and consequently may aid in optimizing parameter settings in individual patients.

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Marwan Hariz, Loránd Eröss, Gun-Marie Hariz, Botond Eröss, Laura Cif, Patric Blomstedt, and Yves Agid

Recently, a series of historical reports portrayed the first women neurosurgeons in various countries. One such woman, a pioneer on many levels, remained unrecognized: Judith Balkányi-Lepintre. She was the first woman neurosurgeon in France, the first woman war neurosurgeon for the French Army, and the first woman pediatric neurosurgeon in France. Born in 1912 to a Hungarian Jewish family, she graduated with honors from medical school in Budapest in 1935, then moved to Paris where she started neurosurgical training in 1937 at L’Hôpital de la Pitié under the mentorship of Clovis Vincent, the founder of French neurosurgery. Shortly after marrying a French colleague in 1940, she had to escape the Geheime Staatspolizei (Gestapo) in Paris and ended up in Algeria, where she joined the French Army of De Gaulle. As a neurosurgeon, she participated in the campaigns of Italy and France between 1943 and 1945. After the war, she returned to work at La Pitié Hospital. In 1947, she defended her doctoral thesis, “Treatment of cranio-cerebral wounds by projectiles and their early complications.” Soon thereafter, she joined Europe’s first dedicated children’s hospital, Hôpital Necker-Enfants Malades in Paris, and contributed to the establishment of pediatric neurosurgery in France. She remained clinically and academically active at Necker until her death in 1982 but was never promoted.

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Brigitte Biolsi, Laura Cif, Hassan El Fertit, Santiago Gil Robles, and Philippe Coubes

Deep brain stimulation is now accepted as a safe and efficient treatment for movement disorders including selected types of dystonia and dyskinesia. Very little, however, is known about its effect on other movement disorders, particularly for “choreic” movements. Huntington disease is a fatal autosomal-dominant neurodegenerative disorder characterized by movement disorders, progressive cognitive impairment, and psychiatric symptoms. Bilateral chronic stimulation of the internal globus pallidus was performed to control choreic movements in a 60-year-old man with a 10-year history of Huntington disease. Chronic deep brain stimulation resulted in remarkable improvement of choreic movements. Postoperative improvement was sustained after 4 years of follow-up with a marked improvement in daily quality of life.

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Nathalie Vayssiere, Niels van der Gaag, Laura Cif, Simone Hemm, Regis Verdier, Philippe Frerebeau, and Philippe Coubes

Object. In patients with dystonia, symptoms vary greatly in their extent and severity. The efficacy of pallidal stimulation is now established, but an interindividual variability in the responses to this treatment exists. A retrospective analysis of postoperative magnetic resonance (MR) images demonstrated millimetric variations in the positions of electrode contacts inside the posterolateroventral portion of the globus pallidus internus (GPi). It therefore seemed very likely that there is a somatotopic organization within the GPi. The goal of this study was to examine the positions of specific electrode contacts according to patients' clinical evolution, so that a somatotopic organization within the GPi could be defined.

Methods. This study included 19 patients (17 of whom were right handed) with generalized dystonia who were treated by bilateral stimulation of the GPi. Patients were examined pre- and postoperatively by using the Burke-Fahn-Marsden Dystonia Rating Scale. Dividing the patient's body into three parts—cervicoaxial area, superior limb, and inferior limb—we determined the following: 1) where the dystonic symptoms started; 2) where symptoms predominated at the time of surgery; and 3) where the highest postoperative improvement was observed.

Variations in clinical response were correlated to the positions of the electrode contacts. All activated electrode contacts were in the posterolateroventral portion of the GPi (Laitinen target). A correlation between the contact location measured longitudinally and the part of the body in which the highest improvement was observed (three different areas; p = 0.004) showed that a location more anterior for the inferior limb and one more posterior for the superior limb were delineated for the right side, but not for the left side.

Conclusions. Inside the posterolateroventral subvolume of the GPi on the right side, three statistically different locations of electrode contacts were determined to be primary deep brain stimulation treatment sites for particular body parts in cases of dystonia.

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Nathalie Vayssiere, Simone Hemm, Laura Cif, Marie Christine Picot, Nina Diakonova, Hassan El Fertit, Philippe Frerebeau, and Philippe Coubes

Object. To assess the validity of relying on atlases during stereotactic neurosurgery, the authors compared target coordinates in the globus pallidus internus (GPi) obtained using magnetic resonance (MR) imaging with those determined using an atlas. The targets were used in deep brain stimulation (DBS) for the treatment of generalized dystonia.

Methods. Thirty-five patients, who were treated using bilateral DBS of the GPi, were included in this study. The target was selected on three-dimensional MR images by direct visual recognition of the GPi. The coordinates were automatically recorded using dedicated software. They were translated into the anterior commissure—posterior commissure (AC—PC) coordinate system by using a matrix transformation process. The same GPi target was defined, based on the locations of brain structures shown in the atlases of Schaltenbrand and Talairach. Magnetic resonance imaging—based GPi target coordinates were statistically compared with the corresponding atlas-based coordinates by applying the Student t-test.

A significant difference (p < 0.001) was demonstrated in x, y, and z directions between MR imaging—based and Schaltenbrand atlas—derived target coordinates. The comparison with normalized Talairach atlas coordinates demonstrated a significant difference (p < 0.01) in the y and z directions, although not in the x direction (p = 0.12).

No significant correlation existed between MR imaging—based target coordinates and patient age (p > 0.1). No significant correlation was observed between MR imaging—based target coordinates and patient sex in the y and z directions (p > 0.9), although it was significant in the x direction (p < 0.05). A significant variation in coordinates and the length of the AC—PC line was revealed only in the y direction (p < 0.005).

Conclusions. A significant difference was found between target coordinates obtained by direct visual targeting on MR images (validated by postoperative clinical results) and those obtained by indirect targeting based on atlases.

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Laura Cif, Victoria Gonzalez-Martinez, Xavier Vasques, Astrid Corlobé, Ana Maria Moura, Alain Bonafé, and Philippe Coubes


Deep brain stimulation (DBS) is used for treating various types of dystonia. Multiple electrodes could be proposed to improve the therapeutic outcome enabling the targeting of specific neuronal populations not reached by the electrical field generated by the initially implanted electrode. The authors address the question of the feasibility and safety of staged multiple lead implantations in the sensorimotor internal globus pallidus (GPi) in primary generalized dystonia (PGD). Criteria for patient selection, surgical technique, target selection, electrical settings management, and clinical outcome are presented.


Sixteen patients (8 harbored the DYT1 gene mutation) presented with PGD and were enrolled in this study. Patients underwent clinical assessment using the Burke-Fahn-Marsden Dystonia Rating Scale preoperatively and during follow-up with DBS. Prior to the addition of electrodes, the authors confirmed, by turning off stimulation, that the patient was still benefiting from DBS and that DBS settings adjustment did not provide further improvement. The second target was defined according to the position of the first electrode, to the residual volume within the sensorimotor GPi, and according to residual symptoms. The second surgery followed the same protocol as the first and the new electrode were inserted using the same bur hole as the first electrode.


The addition of a new pair of electrodes was followed by significant improvement in the whole population (p = 0.005), as well as in the DYT1-negative subgroup (p = 0.012) but not in the DYT1 subgroup (p = not significant). Nevertheless, some patients did not exhibit significant additional benefit. Seven hardware-related complications occurred during the entire follow-up, 3 prior to it, and 4 after the addition of the second pair of electrodes.


The addition of a second pair of electrodes in the GPi in patients with PGD with suboptimal or decaying benefit following the first surgery seems to be a safe procedure and is not followed by an increase in surgery-related complications. This staged procedure may provide further clinical improvement in patients with PGD in whom DBS effect is initially incomplete or when disease progression occurs over time. The position of the additional electrode within the GPi is determined by the available volume within the posteroventral GPi and by the distribution of the dystonic symptoms that need to be controlled.

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Xavier Vasques, Laura Cif, Olivier Hess, Sophie Gavarini, Gerard Mennessier, and Philippe Coubes


Given that improvement is variable from one patient to another, the authors analyzed the impact of globus pallidus internus (GPi) volume on the result of deep brain stimulation (DBS) by comparing highly and less improved patients with primary dystonodyskinetic syndromes.


A stereotactic model was developed to visualize and quantify the relationship between the isofield lines generated by the DBS lead and GPi target. The model was used in 30 right-handed selected patients with primary dystonodyskinetic syndromes who had been treated using bilateral stimulation of the sensorimotor GPi. Ten healthy control individuals were also included in the study. First, the authors compared the GPi volumes between patients and healthy controls. Second, the stimulated GPi volumes, that is, the intersection between the volume of each isofield value and the GPi volumes, were compared between less improved and highly improved patients.


Improvement in the Burke-Fahn-Marsden Dystonia Rating Scale's motor score was rated > 90% in 20 patients (97 ± 4.6%) and < 60% in 10 patients (56.9 ± 6%). The mean volume of the right (461.8 ± 81.8 mm3) and left (406.6 ± 113.2 mm3) GPi in patients showing less response to DBS was significantly smaller than the GPi volume of patients who responded well (right 539.9 ± 86.6 mm3, left 510.6 ± 88.7 mm3) and healthy controls (right 557.8 ± 109.1 mm3, left 525.1 ± 40.8 mm3).


On the left side, the mean stimulated volumes (isofield line range 0.2–1 V/mm) were significantly larger in highly improved than in less improved patients. In this model, the threshold for functional effect was calculated at 0.2 V/mm.

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Philippe Coubes, Laura Cif, Hassan El Fertit, Simone Hemm, Nathalie Vayssiere, Stephanie Serrat, Marie Christine Picot, Sylvie Tuffery, Mireille Claustres, Bernard Echenne, and Philippe Frerebeau

Object. Primary generalized dystonia (PGD) is a medically refractory disease of the brain causing twisting or spasmodic movements and abnormal postures. In more than 30% of cases it is associated with the autosomal DYT1 mutation. Continuous electrical stimulation of the globus pallidus internus (GPi) has been used successfully in the treatment of PGD. The aim of this study was to examine the long-term efficacy and safety of deep brain stimulation (DBS) in the treatment of PGD in children and adults with and without the DYT1 mutation.

Methods. Thirty-one patients with PGD were selected for surgery. Electrodes were bilaterally implanted under stereotactic guidance and connected to neurostimulators that were inserted subcutaneously. Efficacy was evaluated by comparing scores on the clinical and functional Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) before and after implantation.

The efficacy of stimulation improved with time. After 2 years, compared with preoperative values, the mean (± standard deviation) clinical and functional BFMDRS scores had improved by 79 ± 19% and 65 ± 33%, respectively. At the 2-year follow-up examination the improvement was comparable in patients with and without the DYT1 mutation in both the functional (p = 0.12) and clinical (p = 0.33) scores. Children displayed greater improvements in the clinical score than adult patients (p = 0.04) at 2 years of follow up. In contrast, there was no significant difference in functional scores between children and adults (p = 0.95).

Conclusions. Electrical stimulation of the GPi is an effective, reversible, and adaptable treatment for PGD and should be considered for conditions refractory to pharmaceutical therapies.

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Nathalie Vayssiere, Simone Hemm, Michel Zanca, Marie Christine Picot, Alain Bonafe, Laura Cif, Philippe Frerebeau, and Philippe Coubes

Object. The actual distortion present in a given series of magnetic resonance (MR) images is difficult to establish. The purpose of this study was to validate an MR imaging—based methodology for stereotactic targeting of the internal globus pallidus during electrode implantation in children in whom general anesthesia had been induced.

Methods. Twelve children (mean follow up 1 year) suffering from generalized dystonia were treated with deep brain stimulation by using a head frame and MR imaging. To analyze the influence of distortions at every step of the procedure, the geometrical characteristics of the frame were first controlled using the localizer as a phantom. Then pre- and postoperative coordinates of fixed anatomical landmarks and electrode positions, both determined with the head frame in place, were statistically compared.

No significant difference was observed between theoretical and measured dimensions of the localizer (Student's t-test, |t| > 2.2 for 12 patients) in the x, y, and z directions.

No significant differences were observed (Wilcoxon paired-sample test) between the following: 1) pre- and postoperative coordinates of the anterior commissure (AC) (Δx = 0.3 ± 0.29 mm and Δy = 0.34 ± 0.32 mm) and posterior commissure (PC) (Δx = 0.15 ± 0.18 mm and Δy = 0.34 ± 0.25 mm); 2) pre- and postoperative AC—PC distance (ΔL = 0.33 ± 0.22 mm); and 3) preoperative target and final electrode position coordinates (Δx = 0.24 ± 0.22 mm; Δy = 0.19 ± 0.16 mm).

Conclusions. In the authors' center, MR imaging distortions did not induce detectable errors during stereotactic surgery in dystonic children. Target localization and electrode implantation could be achieved using MR imaging alone after induction of general anesthesia. The remarkable postoperative improvement in these patients confirmed the accuracy of the procedure (Burke—Marsden—Fahn Dystonia Rating Scale score Δ = −83.8%).

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Victoria Gonzalez, Laura Cif, Brigitte Biolsi, Sara Garcia-Ptacek, Anne Seychelles, Emily Sanrey, Irene Descours, Christine Coubes, Ana-Maria Ribeiro de Moura, Astrid Corlobe, Syril James, Thomas Roujeau, and Philippe Coubes


To date, experience of globus pallidus internus (GPi) deep brain stimulation (DBS) in the treatment of Huntington's disease (HD) has been limited to a small number of case reports. The aim of this study was to analyze long-term motor outcome of a cohort of HD patients treated with GPi DBS.


Seven patients with pharmacologically resistant chorea and functional impairment were included in a prospective open-label study from 2008 to 2011. The main outcome measure was the motor section of the Unified Huntington's Disease Rating Scale. The primary end point was reduction of chorea.


Patients underwent MRI-guided bilateral GPi implantation. The median duration of follow-up was 3 years. A significant reduction of chorea was observed in all patients, with sustained therapeutic effect; the mean improvement on the chorea subscore was 58.34% at the 12-month follow-up visit (p = 0.018) and 59.8% at the 3-year visit (p = 0.040). Bradykinesia and dystonia showed a nonsignificant trend toward progressive worsening related to disease evolution and partly to DBS. The frequency of stimulation was 130 Hz for all patients. DBS-induced bradykinesia was managed by pulse-width reduction or bipolar settings. Levodopa mildly improved bradykinesia in 4 patients. Regular off-stimulation tests confirmed a persistent therapeutic effect of DBS on chorea.


GPi DBS may provide sustained chorea improvement in selected HD patients with pharmacologically resistant chorea, with transient benefit in physical aspects of quality of life before progression of behavioral and cognitive disorders. DBS therapy did not improve dystonia or bradykinesia. Further studies including quality of life measures are needed to evaluate the impact of DBS in the long-term outcome of HD.