Background: Myoclonus dystonia related to epsilonsarcoglycan gene mutations is characterized by myoclonic jerks and mild to moderate dystonia. The role of basal ganglia dysfunction in the pathogenesis is unknown.Methods: Pallidal neuronal activity was recorded in six nnyoclonus dystonia and six primary generalized dystonia patients operated on for internal globus pallidus deep brain stimulation. In myoclonus dystonia patients compared with primary-dystonia patients, internal pallidum neurons showed higher burst frequency, lower mean burst, and pause durations. External pallidum neurons showed higher mean pause frequency. Oscillatory activity was present in 33% and 35% of internal pallidum neurons in myoclonus dystonia and primary-dystonia patients, respectively, predominantly in the theta frequency band (3-8 Hz).Results: In myoclonus dystonia patients with more severe myoclonus, internal pallidum neurons exhibited a higher bursting activity with high intraburst frequency and lower oscillatory activity frequency.Conclusions: Myoclonus dystonia appears to be related to specific changes in internal pallidum activity, leading to disruption in striato-pallido-thalarno-cortical circuits. (C) 2015 International Parkinson and Movement Disorder Society

Objective: To further determine the causes of variable outcome from deep brain stimulation of the subthalamic nucleus (DBS-STN) in patients with Parkinson disease (PD). Methods: Data were obtained from our cohort of 309 patients with PD who underwent DBS-STN between 1996 and 2009. We examined the relationship between the 1-year motor, cognitive, and psychiatric outcomes and (1) preoperative PD clinical features, (2) MRI measures, (3) surgical procedure, and (4) locations of therapeutic contacts. Results: Pre- and postoperative results were obtained in 262 patients with PD. The best motor outcome was obtained when stimulating contacts were located within the STN as compared with the zona incerta (64% vs 49% improvement). Eighteen percent of the patients presented a postoperative cognitive decline, which was found to be principally related to the surgical procedure. Other factors predictive of poor cognitive outcome were perioperative confusion and psychosis. Nineteen patients showed a stimulation-induced hypomania, which was related to both the form of the disease (younger age, shorter disease duration, higher levodopa responsiveness) and the ventral contact location. Postoperative depression was more frequent in patients already showing preoperative depressive and/or residual axial motor symptoms. Conclusion: In this homogeneous cohort of patients with PD, we showed that (1) the STN is the best target to improve motor symptoms, (2) postoperative cognitive deficit is mainly related to the surgery itself, and (3) stimulation-induced hypomania is related to a combination of both the disease characteristics and a more ventral STN location.

Introduction Deep brain stimulation (DBS) is an established surgical treatment for Parkinson’s disease (PD), essential tremor and dystonia. It is generally acknowledged that the development of DBS as we know it today started with the publication of Benabid, Pollak et al in 1987 on thalamic DBS for tremor. However stereotactic surgery for PD was very common in the pre-levodopa era, and the vast majority of surgical procedures consisted of lesions, mainly pallidotomy, thalamotomy and subthalamotomy. Surgery for PD almost stopped following the introduction of l-dopa therapy in the late 60s. Unilateral thalamotomy continued to be performed rarely and in few centers for patients with intractable tremor. It is generally acknowledged that the publication that marked the “official” birth of DBS was that of Benabid, Pollak and co-workers of 1987 on “Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease”. There is no doubt that it is the fruitful cooperation of neurosurgeon Alim-Louis Benabid and neurologist Pierre Pollak, and especially their introduction of DBS in the subthalamic nucleus in 1993 that founded DBS as we know it today. During the 60s, Sem-Jacobsen and others implanted externalized electrodes which were used for intermittent stimulation and evaluation during weeks or months, prior to subsequent ablation of thalamic and other basal ganglia targets. In the early 70s Bechtereva treated PD patients using “therapeutic electrical stimulation” through electrodes implanted for up to 1.5 years. In the late 70s and early 80s the term Deep Brain Stimulation became commonly used and few groups attempted treatment of Parkinson’s disease, non-Parkinsonian tremor and dystonia with high-frequency stimulation using chronically implanted DBS systems. It is to the credit of the Grenoble Group to have reinvented, modernized and expanded modern DBS in surgical treatment of movement disorders. Deep brain stimulation (DBS) is today an established treatment for advanced Parkinson’s disease (PD), essential tremor and dystonia. New indications for, and applications of, DBS in various brain targets for various neurological and psychiatric illnesses are being reviewed here.

Objective: To understand why some PD patients developed a cognitive decline in the year following STN-HFS. Background STN-HFS is efficient in alleviating parkinsonian motor signs. However, some patients developed a decline in cognitive function after surgery. Design/Methods: Between 02/1996 and 07/2009, 309 PD patients were operated for STN-HFS in the GHPS. Patients were evaluated before and one year after surgery with: 1) neuropsychological and 2) psychiatric tests, 3) parkinsonian disability scales (UPDRS parts I to VI). Precise location of stimulating contacts was obtained using an adjustable three-dimensional atlas of the basal ganglia. The stimulation parameters and levodopa equivalent dosage were reported. A voxel-based-morphometry was also performed on the pre-operative MRI of the patients. Postoperative cognitive decline was defined as a decrease more than 1 SD in the MDRS one year after surgery and/or MDRS Results: Two-hundred fifty-four patients were included in the final statistical analysis. Forty-five (21,5%) presented a decrease in the MDRS score more than 6 points (n=31) and/or a MDRS score under 130 (n=14). No statistical difference in the preoperative clinical characteristics was found between PD patients with vs without postoperative cognitive decline. Patients with postoperative cognitive decline presented a higher rate of postoperative confusion and/or psychiatric troubles. They showed a lower improvement in parkinsonian motor disability and activities of daily living with STN-HFS. The decrease in antiparkinsonian treatment and levodopa-induced complications was not different between the two patients groups. In patients with cognitive decline, the stimulating contacts were located more posteriorly and ventrally, and the frequency of stimulation was lower. Conclusions: STN-HFS may be deleterious for cognitive function, in particular when located in the more ventral part of the STN, thought to process cognitive and emotional information. Disclosure: Dr. Welter has nothing to disclose. Dr. Czernecki has nothing to disclose. Dr. Schupbach has received personal compensation for activities with Medtronic, Inc. and Lundbeck. Dr. Fernandez-Vidal has nothing to disclose. Dr. Karachi has nothing to disclose. Dr. Navarro has nothing to disclose. Dr. Cornu has nothing to disclose. Dr. Pidoux has nothing to disclose. Dr. Mallet has nothing to disclose. Dr. Dormont has nothing to disclose. Dr. Vidailhet has nothing to disclose. Dr. Grabli has nothing to disclose. Dr. Bonnet has nothing to disclose. Dr. Belaid has nothing to disclose. Dr. Houeto has nothing to disclose. Dr. Bardinet has nothing to disclose. Dr. Yelnik has nothing to disclose. Dr. Agid has nothing to disclose.

OBJECTIVETo assess the efficacy of bilateral deep brain stimulation of the internal pallidum in patients with myoclonus-dystonia due to genetically proved ε-sarcoglycan (SGCE-M-D) deficiency.DESIGNPatients with documented SGCE-M-D undergoing bilateral deep brain stimulation of the internal pallidum were recruited. Standardized assessments of M-D were videorecorded before surgery and 6 to 9 months and 15 to 18 months after surgery, using the movement and disability subscales of the Burke-Fahn-Marsden Dystonia Rating Scale and the Unified Myoclonus Rating Scale. The analysis was based on blinded evaluation of the recordings.SETTINGMovement disorder unit in a university hospital in Paris.PATIENTSFive consecutive patients with documented SGCE-M-D.MAIN OUTCOME MEASURESMyoclonus and dystonia scores at follow-up.RESULTSThe median myoclonus score decreased from 76 before surgery (range, 38-116) to 10 at 6 to 9 months after surgery (range, 6-31). The median dystonia score decreased from 30.0 before surgery (range, 18.5-53.0) to 4.5 after surgery (range, 3.5-16.0). Disability was also improved and symptoms remained stable between the postoperative evaluations. No adverse effects occurred.CONCLUSIONSBilateral deep brain stimulation of the internal pallidum is safe and highly effective in this homogeneous population of patients with SGCE-M-D. This therapeutic option should therefore be considered for patients with severe, drug-resistant forms of the disorder.

We assessed the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) or internal pallidum (GPi-DBS) on health-related quality of life (HrQoL) in patients with advanced Parkinson's disease participating in a previously reported multicenter trial. Sickness Impact Profile (SIP) questionnaires were available for analysis in a subgroup of n = 20/20 patients with GPi-DBS and n = 45/49 patients with STN-DBS at baseline, 6 and 36 months. The SIP provides a physical dimension and a psychosocial dimension sum score and 12 category scores: Alertness/Intellectual Behavior (AIB), Ambulation (A), Body Care and Movement (BCM), Communication (C), Eating (E), Emotional Behavior (EB), Home Management (HM), Mobility (M), Recreation and Pastimes (RP), Sleep and Rest (SR), Social Interaction (SI), and Work (W). Motor functioning was assessed by means of the Unified Parkinson's Disease Rating Scale and diaries. At 6 months significant improvements in off-period motor symptoms and activities of daily living were paralleled by significant reductions in the total, physical, and psychosocial SIP score in both treatment groups. At 3 years, sustained improvements were observed in the physical dimension score, BCM, E, M, RP after STN-DBS and M, SI after GPi-DBS. All other SIP subscores approached baseline values, but were still the same or better (except C) whereas motor functioning remained stable after 36 months. STN-DBS and GPi-DBS led to significant early improvements in HrQoL. Despite sustained motor improvements many of these initial benefits were lost after 3 years. This may reflect either progression of the disease or adaptive changes in the subjective perception of health-related wellbeing over time.

Object The localization of any given target in the brain has become a challenging issue because of the increased use of deep brain stimulation to treat Parkinson disease, dystonia, and nonmotor diseases (for example, Tourette syndrome, obsessive compulsive disorders, and depression). The aim of this study was to develop an automated method of adapting an atlas of the human basal ganglia to the brains of individual patients. Methods Magnetic resonance images of the brain specimen were obtained before extraction from the skull and histological processing. Adaptation of the atlas to individual patient anatomy was performed by reshaping the atlas MR images to the images obtained in the individual patient using a hierarchical registration applied to a region of interest centered on the basal ganglia, and then applying the reshaping matrix to the atlas surfaces. Results Results were evaluated by direct visual inspection of the structures visible on MR images and atlas anatomy, by comparison with electrophysiological intraoperative data, and with previous atlas studies in patients with Parkinson disease. The method was both robust and accurate, never failing to provide an anatomically reliable atlas to patient registration. The registration obtained did not exceed a 1-mm mismatch with the electrophysiological signatures in the region of the subthalamic nucleus. Conclusions This registration method applied to the basal ganglia atlas forms a powerful and reliable method for determining deep brain stimulation targets within the basal ganglia of individual patients.

Object. The aim of this study was to correlate the clinical improvement in patients with Parkinson disease (PD) treated using deep brain stimulation (DBS) of the subthalamic nucleus (STN) with the precise anatomical localization of stimulating electrodes. Methods. Localization was determined by superimposing figures from an anatomical atlas with postoperative magnetic resonance (MR) images obtained in each patient. This approach was validated by an analysis of experimental and clinical MR images of the electrode, and the development of a three-dimensional (3D) atlas-MR imaging coregistration method. The PD motor score was assessed through two contacts for each of two electrodes implanted in 10 patients: the "therapeutic contact" and the "distant contact" (that is, the next but one to the therapeutic contact). Seventeen therapeutic contacts were located within or on the border of the STN, most of which were associated with significant improvement of the four PD symptoms tested. Therapeutic contacts located in other structures (zona incerta, lenticular fasciculus, or midbrain reticular formation) were also linked to a significant positive effect. Stimulation applied through distant contacts located in the STN improved symptoms of PD, whereas that delivered through distant contacts in the remaining structures had variable effects ranging from worsening of symptoms to their improvement. Conclusions. The authors have demonstrated that 3D atlas-MR imaging coregistration is a reliable method for the precise localization of DBS electrodes on postoperative MR images. In addition, they have confirmed that although the STN is the main target during DBS treatment for PD, stimulation of surrounding regions, particularly the zona incerta or the lenticular fasciculus, can also improve symptoms of PD.

BACKGROUNDTourette syndrome (TS) is thought to result from dysfunction of the associative-limbic territories of the basal ganglia, and patients with severe symptoms of TS respond poorly to medication. High-frequency stimulation has recently been applied to patients with TS in open studies using the centromedian-parafascicular complex (CM-Pf) of the thalamus, the internal globus pallidus (GPi), or the anterior limb of the internal capsule as the principal target.OBJECTIVETo report the effect of high-frequency stimulation of the CM-Pf and/or the GPi, 2 associative-limbic relays of the basal ganglia, in patients with TS.DESIGNControlled, double-blind, randomized crossover study.SETTINGMedical research.PATIENTSThree patients with severe and medically refractory TS.INTERVENTIONBilateral placement of stimulating electrodes in the CM-Pf (associative-limbic part of the thalamus) and the GPi (ventromedial part).MAIN OUTCOME MEASURESEffects of thalamic, pallidal, simultaneous thalamic and pallidal, and sham stimulation on neurologic, neuropsychological, and psychiatric symptoms.RESULTSA dramatic improvement on the Yale Global Tic Severity Scale was obtained with bilateral stimulation of the GPi (reduction in tic severity of 65%, 96%, and 74% in patients 1, 2, and 3, respectively). Bilateral stimulation of the CM-Pf produced a 64%, 30%, and 40% reduction in tic severity, respectively. The association of thalamic and pallidal stimulation showed no further reduction in tic severity (60%, 43%, and 76%), whereas motor symptoms recurred during the sham condition. No neuropsychological, psychiatric, or other long-term adverse effect was observed.CONCLUSIONSHigh-frequency stimulation of the associative-limbic relay within the basal ganglia circuitry may be an effective treatment of patients with TS, thus heightening the hypothesis of a dysfunction in these structures in the pathophysiologic mechanism of the disorder.

In functional neurosurgery, there is a growing need for accurate localization of the functional targets. Since deep brain stimulation (DBS) of the Vim thalamic nucleus has been proposed for the treatment of Parkinson's disease, the target has evolved toward the globus pallidus and subthalamic nucleus (STN) and the therapeutic indications have enlarged to include psychiatric disorders such as Tourette syndrome or obsessive compulsive disorders. In these pathologies, the target has been restrained to smaller functional subterritories of the basal ganglia, requiring more refined techniques to localize smaller and smaller brain regions, often invisible in routine clinical MRI. Different strategies have been developed to identify such deep brain targets. Direct methods can identify structures in the MRI itself, but only the larger ones. Indirect methods are based on the use of anatomical atlases. The present strategy comprised a 3D histological atlas and the MRI of the same brain specimen, and deformation methodology developped to fit the atlas toward the brain of any given patient. In this paper, this method is evaluated in the aim of being applied to further studies of anatomo-clinical correlation. The accuracy of the method is first discussed, followed by the study of short series of Parkinsonian patients treated by DBS, allowing to compare the deformed atlas with various per- and post-operative data.

BACKGROUND:Based on the basal ganglia model, it has been hypothesized that the efficacy of high-frequency stimulation of the subthalamic nucleus (STN) against parkinsonian symptoms relies on the activation of cortical premotor regions. In previous positron emission tomography activation studies, STN high-frequency stimulation was associated with selective activation of midline premotor areas during hand movements but mainly reduced the regional cerebral blood flow in movement-related areas, peculiarly at rest.OBJECTIVE:To investigate with positron emission tomography the role of regional cerebral blood flow reduction in the clinical improvement provided by STN high-frequency stimulation.METHODS:Seven patients with advanced Parkinson disease, who were markedly improved by bilateral STN high-frequency stimulation, underwent positron emission tomography with H2(15)O while the right STN electrode was turned off. The patients were studied at rest and during right-hand movements in 3 electrode conditions: no stimulation, inefficient low-frequency stimulation, and efficient high-frequency stimulation.RESULTS:The main effect of high-frequency stimulation was to reduce regional cerebral blood flow in the left primary sensorimotor cortex, the lateral premotor cortex, the right cerebellum, and the midline premotor areas. The selective activation of the anterior cingulate cortex and the left primary sensorimotor cortex during hand movement under STN high-frequency stimulation was attributed to decreased regional cerebral blood flow at rest, rather than increased activation induced by STN high-frequency stimulation. Akinesia was correlated with the abnormal overactivity in the contralateral primary sensorimotor cortex and the ipsilateral cerebellum.CONCLUSION:High-frequency stimulation of the STN acts through the reduction of abnormal resting overactivity in the motor system, allowing selective cortical activation during movement.

BACKGROUND High-frequency stimulation of the subthalamic nucleus (STN) is a neurosurgical alternative to medical treatment in levodopa-responsive forms of Parkinson disease. The mechanism of action of STN stimulation remains controversial, although an inhibition of overactive STN neurons has been postulated. OBJECTIVE To determine the effects of high-frequency STN stimulation on the neuronal activity of STN neurons in Parkinson disease patients. PATIENTS Single-unit recordings of the neuronal activity of the STN were obtained before, during, and after the application of intra-STN electrical stimulation in 15 Parkinson disease patients. Changes in firing frequency and pattern were analyzed using various combinations of stimulus frequency (range, 14-140 Hz). RESULTS Stimulation at a frequency greater than 40 Hz applied within the STN significantly decreased the firing frequency and increased the burst-like activity in the firing pattern of STN neurons. An aftereffect was observed in cells that had been totally inhibited during high-frequency stimulation. CONCLUSION The beneficial effects of high-frequency stimulation result from a change in the firing pattern of cellular discharge and a blockade of the spontaneous overactivity of STN neurons.

Movement DisordersVolume 13, Issue 6 p. 969-970 Clinical/Scientific Notes Deep brain stimulation in Parkinson's disease: Opposite effects of stimulation in the pallidum† Dr. Boulos-Paul Bejjani MD, Corresponding Author Dr. Boulos-Paul Bejjani MD Centre d'Investigation Clinique, Inserm V289-Fédération de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceCentre d'investigation Clinique, Groupe Hospitalier Pitie-Salpetriere, 47–83 Boulevard de I'Hopital, 75651 Paris Cedex 13, FranceSearch for more papers by this authorPhilippe Damier MD, Phd, Philippe Damier MD, Phd Centre d'Investigation Clinique, Inserm V289-Fédération de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this authorIsabelle Arnulf MD, Isabelle Arnulf MD Centre d'Investigation Clinique, Inserm V289-Fédération de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this authorSawas Papadopoulos MD, Sawas Papadopoulos MD Centre d'Investigation Clinique, Inserm V289-Fédération de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this authorAnne-Marie Bonnet MD, Anne-Marie Bonnet MD Centre d'Investigation Clinique, Inserm V289-Fédération de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this authorMarie Vidailhet MD, Marie Vidailhet MD Centre d'Investigation Clinique, Inserm V289-Fédération de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this authorYves Agid MD, Phd, Yves Agid MD, Phd Centre d'Investigation Clinique, Inserm V289-Fédération de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this authorBernard Pidoux MD, Phd, Bernard Pidoux MD, Phd Service d'exploration fonctionnelle neurologique, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this authorPhilippe Cornu MD, Philippe Cornu MD Service de neurochirurgie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this authorDidier Dormont MD, Didier Dormont MD Service de neuroradiologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this authorClaude Marsault MD, Claude Marsault MD Service de neuroradiologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this author Dr. Boulos-Paul Bejjani MD, Corresponding Author Dr. Boulos-Paul Bejjani MD Centre d'Investigation Clinique, Inserm V289-Fédération de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceCentre d'investigation Clinique, Groupe Hospitalier Pitie-Salpetriere, 47–83 Boulevard de I'Hopital, 75651 Paris Cedex 13, FranceSearch for more papers by this authorPhilippe Damier MD, Phd, Philippe Damier MD, Phd Centre d'Investigation Clinique, Inserm V289-Fédération de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this authorIsabelle Arnulf MD, Isabelle Arnulf MD Centre d'Investigation Clinique, Inserm V289-Fédération de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this authorSawas Papadopoulos MD, Sawas Papadopoulos MD Centre d'Investigation Clinique, Inserm V289-Fédération de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this authorAnne-Marie Bonnet MD, Anne-Marie Bonnet MD Centre d'Investigation Clinique, Inserm V289-Fédération de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this authorMarie Vidailhet MD, Marie Vidailhet MD Centre d'Investigation Clinique, Inserm V289-Fédération de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this authorYves Agid MD, Phd, Yves Agid MD, Phd Centre d'Investigation Clinique, Inserm V289-Fédération de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this authorBernard Pidoux MD, Phd, Bernard Pidoux MD, Phd Service d'exploration fonctionnelle neurologique, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this authorPhilippe Cornu MD, Philippe Cornu MD Service de neurochirurgie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this authorDidier Dormont MD, Didier Dormont MD Service de neuroradiologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this authorClaude Marsault MD, Claude Marsault MD Service de neuroradiologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceSearch for more papers by this author First published: 04 November 2004 https://doi.org/10.1002/mds.870130618Citations: 30 † A videotape accompanies this article. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume13, Issue6November 1998Pages 969-970 RelatedInformation