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In advanced Parkinson's disease, several therapeutical option including not only lesional surgery (VIM, GPi) and deep brain stimulation (STN, GPi, VIM) but also continuous subcutaneous apomorphine infusion therapy can be proposed to the patient. The choice depends on the hope of the patient, patient's general health condition and the experience and choice of the neurosurgical and neurologist team. Here we report our experience based on 400 STN-DBS cases and we discuss, on the basis of our experience and on the literature, the advantage and disadvantage of DBS strategy as compared with non-surgical option such as continuous subcutaneous apomorphine infusion therapy. [ABSTRACT FROM AUTHOR]

Background: High frequency stimulation of the subthalamic nucleus (STN) is an alternative but expensive neurosurgical treatment for parkinsonian patients with levodopa induced motor complications. Objective: To assess the safety, clinical effects, quality of life, and economic cost of STN stimulation. Methods: 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. Results: 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 before surgery to €1673 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 over 2.2 years. Conclusions: STN stimulation has good outcomes with relatively low risk and little cost burden in PD patients with levodopa induced motor complications. [ABSTRACT FROM AUTHOR]

Introduction. – Parkinson’s disease is a progressive neurodegenerative disorder whose main histopathological feature is the loss of dopaminergic neurons in the pars compacta of the substantia nigra with secondary striatal dopaminergic insufficiency. Treatment relies on medical therapy, using levodopa and dopaminergic agonists. However, the development of treatment complications, including motor fluctuations and levodopa-induced dyskinesia, led to the development of alternative therapeutical strategies such as deep brain stimulation and gene therapy.Exegesis. – Current gene therapy models for Parkinson’s disease have focused on two strategies. The first one is the replacement of biosynthetic enzymes for dopamine synthesis and the second consists in the addition of neurotrophic factors for protection and restoration of dopaminergic neurons.Conclusion. – Neuroprotection and restoration of the nigrostriatal pathway are important issues for future genetic treatment strategies for Parkinson’s disease and could include, in addition to neurotrophic factors, genes to prevent apoptosis or detoxify free radical species. [Copyright &y& Elsevier]

In our center, a physiotherapist is present in the operative room to bring relief to the Parkinsonian patient during subthalamic nucleus stimulation surgery under local anesthesia. This study searched to determine the causes of pain and suffering during bilateral electrode implantation and to assess the role of physiotherapy. Ninety-two consecutive patients operated on between 2001 and 2004 were included in this retrospective study. A questionnaire with eight items was developed and mailed to the patients. Seventy-five responses to questionnaires were available. All patients except one experienced physical pain and psychological suffering, alleviated by physiotherapy. These preliminary results need to be confirmed in a prospective randomized study. [ABSTRACT FROM AUTHOR]

Before the introduction of high frequency stimulation of the subthalamic nucleus (STN), many disabled tremor dominant parkinsonian patients underwent lesioning or chronic electrical stimulation of the thalamus. We studied the effects of STN stimulation in patients with previous ventral intermediate nucleus (VIM) surgery whose motor state worsened. Fifteen parkinsonian patients were included in this study: nine with unilateral and two with bilateral VIM stimulation, three with unilateral thalamotomy, and one with both unilateral thalamotomy and contralateral VIM stimulation. The clinical evaluation consisted of a formal motor assessment using the Unified Parkinson's Disease Rating Scale (UPDRS) and neuropsychological tests encompassing a 50 point frontal scale, the Mattis Dementia Rating Scale, and the Beck Depression Inventory. The first surgical procedure was performed a mean (SD) of 8 (5) years after the onset of disease. STN implantation was carried out 10 (4) years later, and duration of follow up after beginning STN stimulation was 24 (20) months. The UPDRS motor score, tremor score, difficulties in performance of activities of daily living, and levodopa equivalent daily dose significantly decreased after STN stimulation. Neither axial symptoms nor neuropsychological status significantly worsened after the implantation of the STN electrodes. The parkinsonian motor state is greatly improved by bilateral STN stimulation even in patients with previous thalamic surgery, and STN stimulation is more effective than VIM stimulation in tremor dominant parkinsonian patients. [ABSTRACT FROM AUTHOR]

Objective: To compare the influence of low-frequency (10-25 Hz) versus higher (60-80 Hz) frequency stimulation of the pedunculopontine nucleus area (PPNa) on akinaesia, freezing of gait and daytime sleepiness. Method: We included nine patients with Parkinson's disease (PD) and severe gait disorders. In this doubleblind randomised cross-over study, patients were assessed after 24 h of PPNa stimulation. Assessments included the motor part of the Unified Parkinson's Disease Rating Scale, the Epworth Sleepiness Scale and a behavioural gait assessment. Results: Compared with 60-80 Hz, 10-25 Hz PPNa stimulation led to decreased akinaesia, gait difficulties and daytime sleepiness in 7/9 patients. In one patient, these symptoms were aggravated under 10-25 Hz stimulation compared with 60-80 Hz. Conclusion: These results are in keeping with the benefits of chronic PPNa stimulation for gait and postural difficulties in patients with PD, and with regard to the influence of patients' clinical characteristics, differential neuronal loss in the PPNa and electrode location. We conclude that in patients with PPNa stimulation, low frequency provides a better outcome than high-frequency stimulation. [ABSTRACT FROM AUTHOR]

Stimulation of the subthalamic nucleus (STN) improves the cardinal features of Parkinson disease (PD). However, its efficacy on gait disorders is less satisfying in the long term. In recent years, the pedunculopontine (PPN) nucleus has emerged as a possible promising deep brain stimulation target for gait disorders in PD. In this review, we examine whether STN and PPN act synergistically or antagonistically. Results suggest that the combination of STN and PPN stimulations leads to a significant further improvement in gait as compared with STN stimulation alone, but additive effects on the classical motor triad are questionable. Thus, they highlight the specificity of STN stimulation over PPN's for the PD cardinal features and the specificity of PPN stimulation over STN for gait disorders. In addition, low-frequency stimulation of the PPN may improve alertness. The additive rather than potentiating effects of STN and PPN stimulations suggest that they may be mediated by distinct pathways. Nevertheless, considering the inconsistencies in published results regarding the influence of PPN stimulation on gait disorders, work is still needed before one can know whether it will convert into a standard surgical treatment and to decipher its place beside STN stimulation. [ABSTRACT FROM AUTHOR]

Gait disturbances are frequent and disabling in advanced Parkinson's disease. These symptoms respond poorly to usual medical and surgical treatments but were reported to be improved by stimulation of the pedunculopontine nucleus. We studied the effects of stimulating the pedunculopontine nucleus area in six patients with severe freezing of gait, unresponsive to levodopa and subthalamic nucleus stimulation. Electrodes were implanted bilaterally in the pedunculopontine nucleus area. Electrode placement was checked by postoperative magnetic resonance imaging. The primary outcome measures were a composite gait score, freezing of gait questionnaire score and duration of freezing episodes occurring during a walking protocol at baseline and one-year follow-up. A double-blind cross-over study was carried out from months 4 to 6 after surgery with or without pedunculopontine nucleus area stimulation. At one-year follow-up, the duration of freezing episodes under off-drug condition improved, as well as falls related to freezing. The other primary outcome measures did not significantly change, nor did the results during the double-blind evaluation. Individual results showed major improvement of all gait measures in one patient, moderate improvement of some tests in four patients and global worsening in one patient. Stimulation frequency ranged between 15 and 25 Hz. Oscillopsia and limb myoclonus could hinder voltage increase. No serious adverse events occurred. Although freezing of gait can be improved by low-frequency electrical stimulation of the pedunculopontine nucleus area in some patients with Parkinson's disease our overall results are disappointing compared to the high levels of expectation raised by previous open label studies. Further controlled studies are needed to determine whether optimization of patient selection, targeting and setting of stimulation parameters might improve the outcome to a point that could transform this experimental approach to a treatment with a reasonable risk–benefit ratio. [ABSTRACT FROM PUBLISHER]

Objective: To study the pyramidal tract side effects (PTSEs) induced by the spread of current from the subthalamic nucleus (SIN) to the pyramidal tract (PT), in patients with parkinsonism undergoing SIN stimulation. Methods: 14 patients bilaterally implanted with tetrapolar electrodes were assessed. For each side separately, the threshold of adverse effects induced by monopolar stimulation delivered by the chronically used contact was detected. The voltage was progressively increased until the patient experienced discomfort. All the PTSEs induced at 130 Hz (high-frequency stimulation (HFS)) and 2 or 3 Hz (low-frequency stimulation (LFS)) were videotaped. By superimposing the preoperative and postoperative MR images, the minimum distance (R) from the centre of the used contact to the medial border of the PT were measured. Results: The progressive increase in voltage at HFS induced tonic motor contractions, mainly located in the face, in 27/28 electrodes. LFS induced synchronous rhythmic myoclonus in the same territory. PTSEs induced at threshold voltage by HFS were observed in the upper face at 13/28 electrodes (bilaterally in six cases) and in the contralateral lower face at five electrodes. A positive correlation was found between the stimulus intensity capable of eliciting motor contractions at HFS and R. Conclusions: HFS of the SIN preferentially activates the corticobulbar tract over the corticospinal tract. Therefore, cranial motor contractions need to be looked for during electrical parameter setting. The positive correlation between the electrical intensity threshold for PTSEs and R reflects the need for millimetre accuracy in electrode positioning. [ABSTRACT FROM AUTHOR]

Introduction Les troubles de la marche et le freezing – blocage survenant à l’initiation ou en cours de mouvement – sont fréquents et invalidants aux stades avancés de la maladie de Parkinson. Leur réponse aux traitements usuels (dopathérapie et stimulation des noyaux subthalamiques [NST]) est le plus souvent insatisfaisante. La stimulation des noyaux pédonculopontins (NPP) a été récemment proposée comme alternative thérapeutique pour la prise en charge des formes non-répondantes. Les circuits cérébraux sous-jacents, tout comme les mécanismes d’action de cette cible, restent cependant largement méconnus. Matériel et méthode La présente étude se proposait de mieux circonscrire la physiopathologie des troubles dopa-résistants et leur modulation par la stimulation bilatérale des NPP chez des patients doublement implantés (NST/NPP ; n = 3), au moyen de la technique de tomographie par emission de positons (TEP-H2O15), lors d’une tâche d’imagerie motrice de la marche. Les patients ont été scannés stimulation des NPP en marche et à l’arrêt, sous stimulation chronique des NST, à jeun de traitement dopaminergique. Résultats Lors de la réalisation de la tâche mentale, une hypoactivation frontale associée à une hyperactivation pariétale étaient constatées chez les patients, stimulation des NPP éteinte, comparativement aux données obtenues chez des témoins appariés en âge et en genre. Des activations dans l’aire motrice supplémentaire, les noyaux gris centraux, le cervelet et le mésencéphale (NPP, noyaux cunéiformes) étaient par ailleurs retrouvées, stimulation des NPP allumée. Discussion–conclusion La restauration conjointe d’activité de structures fronto-striatales, du cervelet et du mésencéphale sous stimulation bilatérale des NPP pourrait donc contribuer à améliorer la marche parkinsonienne. [ABSTRACT FROM AUTHOR]

We examined executive functioning in patients with Parkinson's disease exhibiting, or not, levodopa-resistant freezing of gait (L-FOG). 38 advanced-stage patients with L-FOG were identified in a consecutive series of 400 patients. They were matched with 38 patients without L-FOG. All patients underwent prospective evaluations of cognitive and motor functioning before subthalamic nucleus surgery, and 1 year after. A composite frontal score, a measure of executive functioning, was compared between the two groups. We also examined correlations between the frontal score and the score on the FOG item of the Unified Parkinson Disease Rating Scale II. Results show that after surgery, patients with L-FOG, as a group, were more impaired in executive functioning than control patients. However, individual data analysis showed preserved executive functions in 11 patients with L-FOG. In addition, there was no correlation between L-FOG severity and the degree of executive impairment. Therefore, frontal dysfunction may be one mechanism underlying L-FOG in a number of patients with Parkinson's disease. However, since some patients develop L-FOG despite the preservation of executive functions, lesions or dysfunction of other neuronal structures are likely to be involved. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: In animals, the pedunculopontine (PPN) and the sub-cuneiform (SCU) nuclei located in the upper brainstem are involved during the processing of gait. Similar functional nuclei are suspected in humans but their role in gait is unclear. Here we show that, using extra-cellular recordings of the PPN/SCU region obtained in two parkinsonian patients, the SCU neurons increased their firing rate without modifying their firing pattern during mimicked steps. We conclude that SCU neurons are activated during gait processes. [Copyright &y& Elsevier]

Background: Long term effects of subthalamic nucleus (STN) stimulation on cognition, mood, and behaviour are unknown.Objective: This study evaluated the cognitive, mood, and behavioural effects of bilateral subthalamic nucleus deep brain stimulation (STN DBS) in patients with Parkinson's disease (PD) followed up for three years.Methods: A consecutive series of 77 PD patients was assessed before, one, and three years after surgery. Mean (SD) age at surgery was 55 (8). Seven patients died or were lost for follow up. Neuropsychological assessment included a global cognitive scale, memory, and frontal tests. Depression was evaluated using the Beck depression inventory. Assessment of thought disorders and apathy was based on the unified Parkinson's disease rating scale. Reports of the behavioural changes are mainly based on interviews done by the same neuropsychologist at each follow up.Results: Only two cognitive variables worsened (category fluency, total score of fluency). Age was a predictor of decline in executive functions. Depression improved whereas apathy and thought disorders worsened. Major behavioural changes were two transient aggressive impulsive episodes, one suicide, four suicide attempts, one permanent apathy, one transient severe depression, four psychoses (one permanent), and five hypomania (one permanent).Conclusions: Comparing baseline, one year, and three year postoperative assessments, STN stimulation did not lead to global cognitive deterioration. Apathy scores mildly increased. Depression scores mildly improved. Behavioural changes were comparatively rare and mostly transient. Single case reports show the major synergistic effects of both medication and stimulation on mood and behaviour, illustrating the importance of a correct postoperative management. [ABSTRACT FROM AUTHOR]

Introduction/Background The pathophysiology of Pisa Syndrome (PS), lateral trunk tilt occurring in the advanced stages of Parkinson's disease (PD), remains to be solved. It might be the consequence of biased spatial referentials. We comprehensively investigated the representation of the vertical (visual-VV and postural-PV), together with that of the long body axis (LBA) in PD patients with PS. Material and method Double-blind controlled trial in 18 PD patients showing PS and treated with bilateral deep brain stimulation (DBS) of the subthalamic nuclei (STN): 63.5 [5.5] years, 11 females, disease duration 17.5 [5.2] years. Spatial estimates were tested off medication under four conditions of stimulation (bilateral on, bilateral off, unilateral on/off, unilateral off/on). Motor state (UPDRS), scoliosis and lateral trunk tilt were also assessed. Twenty healthy age- and gender-matched participants were also included. Results The median lateral trunk tilt was 7.5° (IQD = 5) under the instruction to stand upright. Scoliosis was frequent (67%) reaching 82% in participants with severe PS, of moderate magnitude (16° [12.5]), and side congruent with that of the PS (67%). The correlation between PS and scoliosis (Cobb) magnitude was strong ( r = 0.71, P = 0.008). In contrast no concordance was found between the side of the PS and disease sides (10/18 tilted to the side of the most denervated striatum; 11/18 tilted toward the most affected hemibody). Spatial perceptions were more frequently biased in patients than in controls ( P < 0.05): VV 7/18; PV 6/18; LBA 6/18; but not more severe ( P > 0.05). No statistical rule was found between any of biased referential (side or magnitude) and the trunk tilt (side or magnitude). No spatial referential was modulated by DBS. Conclusion Spatial biases are frequently in PS but are not the cause of the lateral trunk tilt. In contrast scoliosis was not only strongly associated to severe PS. We found a troubling concordance in sides and magnitude. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the occurrence of eosinophilia in four patients who was under medication of continuous apomorphine infusion.