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Objective: To confirm the efficacy and safety of deep brain stimulation (DBS) of the internal part of the globus pallidus in improving severe tardive dyskinesia (TD)., Methods: Nineteen patients with severe pharmacoresistant TD were included. All were assessed at baseline and at 3, 6 (main outcome measure), and 12 months, and in the long term (6-11 years) for 14 patients, after bilateral pallidal DBS, using motor scales (Extrapyramidal Symptoms Rating Scale [ESRS], Abnormal Involuntary Movement Scale [AIMS]), cognitive scales, and a psychiatric assessment. At 6 months, a double-blind ESRS evaluation was performed in the stimulation "on" and stimulation "off" conditions., Results: At 6 months, all patients had a decrease of more than 40% on the ESRS. The efficacy of the procedure was confirmed by a double-blind evaluation. This improvement was maintained at 12 months (ESRS: decrease of 58% [21%-81%];, Aims: decrease of 50% [7%-77%]) and in the long term (ESRS: decrease of 60% [22%-90%];, Aims: decrease of 63% [14%-94%], n = 14). All the subscores of the ESRS (parkinsonism, dystonia, and chorea) and of the AIMS (facial, oral, extremities, and trunk movements) improved. Despite psychiatric comorbidities at baseline, cognitive and psychiatric tolerability of the procedure was excellent. No cognitive decline was observed and mood was improved in most of the patients., Conclusions: Pallidal DBS procedure should be considered as a therapeutic option in disabling TD refractory to medical treatment., Classification of Evidence: This study provides Class II evidence that in patients with severe pharmacoresistant TD with implanted pallidal leads, the stimulation "on" condition significantly improved ESRS scores compared to the stimulation "off" condition., (© 2016 American Academy of Neurology.)

Objective: Studies investigating the effects of subthalamic deep-brain stimulation (DBS-STN) on restless legs syndrome (RLS) in Parkinson's disease (PD) are limited and report conflicting results, with some describing the emergence of RLS after DBS-STN, while others report postoperative improvement of this disorder. Severe decrease in postoperative dopaminergic medications dose, which may unmask RLS symptoms, has been proposed to explain the emergence of RLS after surgery. We aimed to specifically identify factors associated with the risk of developing RLS after DBS-STN in order to enhance our comprehension of the underlying mechanisms contributing to the development of RLS in PD., Patients: In this observational prospective study, we evaluated the occurrence of RLS in 31 patients with PD originally free from RLS symptoms, six months after bilateral chronic DBS-STN, and compared clinical and treatment parameters of patients who developed postoperative RLS with those of patients without postoperative RLS., Results: Six patients out of 31 reported post-operative emergence of RLS. There was no between-group difference in demographic data, pre-operative treatment parameters or clinical improvement measures after DBS-STN. However, PD patients with emergence of RLS after DBS-STN had a higher dose of dopamine agonists at postoperative evaluation compared to PD patients without emergence of RLS (p = 0.040) and a lower percentage of decrease in dopamine agonists (p = 0.043)., Conclusion: Overstimulation resulting from cumulative effects of dopamine agonists and STN-DBS may induce changes in excitability of the dopaminergic system, leading to an emergence of RLS. Clinicians should take into account this phenomenon while adjusting pharmacological treatment after surgery., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To investigate the acute effect of subthalamic nuclei deep brain stimulation (STN-DBS) and levodopa on pain and tolerance thresholds in patients with Parkinson disease. We hypothesized that a modification of pain threshold after STN-DBS would suggest a central modification of pain perception, whereas the absence of pain threshold change after STN-DBS would correspond to a peripheral mechanism via a decrease of painful stimuli., Methods: Nineteen patients with Parkinson disease were included in this double-blind, randomized, crossover study. Postoperatively, we evaluated pain thresholds (thermal and mechanical) and motor symptoms under 3 acute conditions: stimulation on/medication off; stimulation off/medication on; and stimulation off/medication off. We also conducted a retrospective analysis of the data prospectively recorded during the follow-up of the cohort pre- and postoperatively (Unified Parkinson's Disease Rating Scale [UPDRS] score, Hoehn and Yahr stage, equivalent levodopa daily dose, and tapping test score)., Results: We found a significant increase of pain and tolerance mechanical thresholds not only after acute STN-DBS but also after acute levodopa administration. We did not find any significant correlation between postoperative clinical pain improvement and UPDRS-III improvement after acute levodopa or STN-DBS, nor with motor complications improvement assessed with UPDRS-IV after chronic STN-DBS. No correlation was found between postoperative clinical pain improvement and mechanical pain threshold modification., Conclusion: Clinical pain alleviation after STN-DBS cannot be considered merely as a consequence of motor complications improvement and could be attributable to a direct central modulation of pain perception, via increased mechanical pain and tolerance thresholds.

Deep brain stimulation of the subthalamic nucleus (DBS) is a widely used surgical technique to suppress motor symptoms in Parkinson's disease (PD), and as such improves patients' quality of life. However, DBS may produce emotional disorders such as a reduced ability to recognize emotional facial expressions (EFE). Previous studies have not considered the fact that DBS and l-dopa medication can have differential, common, or complementary consequences on EFE processing. A thorough way of investigating the effect of DBS and l-dopa medication in greater detail is to compare patients' performances after surgery, with the two therapies either being administered ('on') or not administered ('off'). We therefore used a four-condition (l-dopa 'on'/DBS 'on', l-dopa 'on'/DBS 'off', l-dopa 'off'/DBS 'on', and l-dopa 'off'/DBS 'off') EFE recognition paradigm and compared implanted PD patients to healthy controls. The results confirmed those of previous studies, yielding a significant impairment in the detection of some facial expressions relative to controls. Disgust recognition was impaired when patients were 'off' l-dopa and 'on' DBS, and fear recognition impaired when 'off' of both therapies. More interestingly, the combined effect of both DBS and l-dopa administration seems much more beneficial for EFE recognition than the separate administration of each individual therapy. We discuss the implications of these findings in the light of the inverted U curve function that describes the differential effects of dopamine level on the right orbitofrontal cortex (OFC). We propose that, while l-dopa could "overdose" in dopamine the ventral stream of the OFC, DBS would compensate for this over-activation by decreasing OFC activity, thereby restoring the necessary OFC-amygdala interaction. Another finding is that, when collapsing over all treatment conditions, PD patients recognized more neutral faces than the matched controls, a result that concurs with embodiment theories., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Deep brain stimulation (DBS) is a neurosurgical technique that has now been available for some 25 years. It is used in the treatment of various motor disorders, e.g. Parkinson's disease (PD), essential tremor and dystonia, and neuropsychiatric illnesses, e.g. obsessive-compulsive disorder and Tourette syndrome. The surgical targets of DBS include the thalamic ventralis intermedius nucleus (Vim), the globus pallidus internus (GPi) and more recently the subthalamic nucleus (STN), currently considered as the reference target in the treatment of PD. In the last ten years, most studies in PD patients have described a rapid and marked weight gain in the months following DBS of the STN. This weight gain sometimes induces obesity and can have metabolic repercussions. The physiopathological mechanisms responsible for the weight gain are multifactorial (changes in energy metabolism and eating behaviour, reduction of motor complications, etc.). This review reports current knowledge concerning weight changes in patients treated by DBS with different surgical targets. It also describes the mechanisms responsible for weight gain and the health outcome for the patients., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Hypomanic symptoms depending on anatomical location of contacts are reported in patients with Parkinson's disease (PD) treated by deep brain stimulation (DBS) of the subthalamic nucleus (STN). However, the underlying cortical and subcortical dysfunction is debated. In this study, five PD patients implanted with DBS-STN who presented with reversible and reproducible hypomanic symptoms after stimulation of specific 'manic' contacts were investigated. Hypomanic symptoms were assessed using the Bech and Rafaelsen Mania Scale (MAS). Three dimensional anatomical location of 'euthymic' and 'manic' contacts, after matching the postoperative CT scan with the preoperative stereotactic MRI, and a H(2)(15)O positron emission tomography (PET) study testing 'euthymic' and 'manic' contacts, were performed. Under 'euthymic' conditions, MAS score (mean±SD) was 0.6±0.5 compared with 7.8±3.1 under 'manic' conditions. Nine of 10 'manic' contacts were located in the substantia nigra, mainly in its ventral part. PET showed that hypomania was associated with strong asymmetrical cerebral activation involving preferentially the right hemisphere and was mediated by activation of the anterior cingulate and medial prefrontal cortex. The present study demonstrates the role of the subcortical structures in the genesis of hypomania in PD patients treated with DBS and stresses the involvement of the substantia nigra.

Background: Deep brain stimulation (DBS) in Parkinson's disease uses bi-hemispheric high-frequency stimulation within the subthalamus, however, the specific impacts of bilaterality of DBS are still not clear. Thus, we aimed to study the individual-level clinical impact of locations of right-left contact pair-up accounting for each subthalamic nucleus (STN) anatomy. Methods: Contact locations and effects at 1 year were studied retrospectively in an unselected series of 53 patients operated between 2004 and 2010. Location of contacts was defined relatively to the main axis of STN used to map longitudinal and transversal positions, and STN membership (out meaning out-of-STN). Contact pairings were described via three methods (i) Unified contact location (UCL) collapsing DBS into an all-in-one contact (ii) balance of contact pair-up (BCPU), defined as symmetric or asymmetric regardless of laterality (iii) hemisphere-wise most frequent contact pair-up (MFCP) regardless of BCPU. Clinical data were mean levodopa equivalent dose, Unified Parkinson's Disease Rating Scale (UPDRS) motor score III without medication, UPDRS II and III speech sub-scores, UPDRS II freezing sub-score, 1 year versus preoperative values, with and without levodopa. Ad-hoc two-sided tests were used for statistical analysis. Results: Worsening speech, was more frequent for UCL_out patients and when the left MFCP contact was rear and or superolateral, however, it less frequent for BCPU-asymmetric patients. Worsening freezing was more frequent when the right MFCP contact was rear and superolateral. Conclusions: These results point to strategies for minimizing dysarthria and freezing as adverse effects of DBS. [ABSTRACT FROM AUTHOR]

Subthalamic nucleus (STN) targeting is classically performed based on AC-PC probabilistic position. Nevertheless, MRI allows direct visualization and targeting. We aimed to compare the position localized on MR images with standard stereotactic diagrams. The STN was manually contoured on MR images (22 Parkinson’s disease patients); boundaries were simplified in a schematic polygonal form. Front and lateral stereotactic diagrams were constructed according to Talairach and Benabid. We compared x, y and z coordinates of the geometrical center of MRI-based polygons and stereotactic diagrams (Wilcoxon matched-pairs tests). There was significant discordance between MRI-based polygons and AC-PC-based images. MRI shows the STN as more posterior, medial and slightly inferior. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]