INTRODUÇÃO: Os efeitos da levodopa (LD) e da estimulação cerebral profunda (ECP) de núcleo subtalâmico (STN) sobre o equilíbrio e sintomas axiais são até o momento controversos. OBJETIVOS: Avaliar quantitativamente os efeitos da ECP de STN e da LD sobre o equilíbrio estático em pacientes com DP operados, em comparação com a LD em pacientes não operados. MÉTODOS: Trinta e um pacientes submetidos a ECP de STN entre 3 meses e 1 ano e meio antes da avaliação e 26 controles portadores de DP não operados, estágios Hoehn e Yahr 2 a 4 foram avaliados usando UPDRS para avaliação clínica e plataforma de força para avaliar oscilações posturais. O primeiro grupo foi avaliado com ECP e sem medicação, com ECP e com medicação e sem ECP e sem medicação. O segundo grupo foi avaliado com e sem medicação. Cada paciente foi avaliado com os olhos abertos e fechados. O deslocamento do centro de pressão anteroposterior, laterolateral, a área, velocidade e deslocamento total linear foram medidos pela plataforma de força. Os dados paramétricos foram comparados usando o teste t de Student e os dados não-paramétricos foram comparados pelo teste de Kruskal-Wallis. A avaliação clínica consistiu na parte 3 da escala UPDRS e na escala Hoehn e Yahr. Nível de significância estatística considerada foi p=0,05. RESULTADOS: Os pacientes não operados oscilaram mais quando sob efeito da levodopa do que sem medicação. No grupo operado, a maior oscilação é no grupo com ECP desligada e sem medicação. Tende a reduzir sob efeito da ECP apresenta redução significativa sob efeito simultâneo de ECP e levodopa. CONCLUSÃO: A associação da ECP de NST com medicação tem impacto positivo sobre o controle postural. O efeito da ECP de NST reverte o efeito negativo da levodopa sobre as oscilações observadas em pacientes não operados / INTRODUCTION: The effects of bilateral subthalamic (STN) DBS and medication on balance and on axial symptoms in PD have been so far inconsistent. OBJECTIVE: To assess quantitatively the effects of DBS on static balance in PD. METHODS: Thirty-one patients submitted to STN DBS over 3 months before and 26 non-operated controls with PD on Hoehn & Yahr stage \"on\" 2 to 4 were evaluated using UPDRS and a force plate to measure sway. The first group was evaluated on-DBS/off-medication, on-DBS/on-medication and off-DBS/off-medication. The second group was evaluated on and off medication. Each group was assessed with eyes open and then closed. Antero-posterior, laterolateral postural displacements of the center of pressure (COP), as well as 95% sway area, path length and speed of oscillation were analyzed and compared using t-Student test for parametrical data and Kruskal-Wallis test for non-parametrical data. Level of significance was set to p < 0.05. Clinical assessment consisted of UPDRS part 3 and Hoehn & Yahr scores for each of the conditions. RESULTS: Control patients tended to oscillate more in the on medication condition than off medication. DBS patients tended to oscillate more in the off-DBS/off medication condition, with a tendency to decrease the sway when on DBS/off medication with additional decrease when on DBS/on medication. CONCLUSION: Association of bilateral STN DBS and medication positively influences postural control in PD and surgery reverses the tendency of medication to increase body sway in non-operated patients

A estimulação cerebral profunda do núcleo subtalâmico (NST) é um tratamento bem estabelecido para os sintomas refratários à medicação em paciente com doença de Parkinson avançada. Além do procedimento de implante, a programação dos eletrodos é uma etapa fundamental para atingir os resultados desejados. A primeira etapa da programação é estabelecer os limiares para efeitos adversos. Contudo, a correlação entre a localização do eletrodo e o limiar para efeitos adversos associados à estimulacao das estruturas adjacentes ainda não é bem estabelecida. Características neuroanatômicas e a localização dos eletrodos foram identificadas utilizando-se um programa de planejamento de cirurgia estereotáxica, enquanto os parâmetros de estimulação e os efeitos adversos foram obtidos dos prontuários médicos. As correlações entre estas variáveis foram testadas através de análises univariadas e análises multivariadas. Estimulação monopolar produziu efeitos adversos capsulares (EA-C) em 208 dos 316 contatos (65,8%) e efeitos adversos não-capsulares (EA-NC) em 223 dos 316 contatos (70,6%). A ocorrência de EA-C esteve associada com o número do contato (p = 0,009) e com a coordenada \"Z\" (p = 0,03), enquanto o limiar de voltagem para EA-C esteve correlacionado com o ângulo da cápsula interna (p = 0,035). A ocorrência de EA-NC esteve associada com o número do contato (p = 0,005), \"X\" (p = 0,03), \"Y\" (p = 0,004) e com a distância para o núcleo rubro (p = 0,001 e p = 0,003). Houve correlação entre o limiar de voltagem para EA-NC e o ângulo da cápsula interna (p = 0,006), o ângulo coronal do eletrodo (p = 0,02), \"X\" (p = 0,001), \"Y\" (p < 0,001), \"Z\" (p < 0,001) e com as distâncias para a cápsula interna (p = 0,02) e para o núcleo rubro (p = 0,004 e p < 0,001). EA-C estiveram associados com os contatos mais distais do eletrodo e com localização mais profunda, bem como com maior angulação da cápsula interna. EA-NC estiveram associados com os contatos mais distais do eletrodo, localizados mais medial, posterior e inferiormente e mais próximos do núcleo rubro. Ademais, houve associação entre EA-NC e eletrodos implantados com maior ângulo coronal, bem como com maior angulação da cápsula interna. Estes achados poderão ser úteis no desenvolvimento de novas estratégias para o planejamento do implante de eletrodos de estimulação cerebral profunda. / Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for medically refractory motor symptoms of patients with advanced Parkinson\'s disease. Programming of the device is as relevant to patient outcome as accurate implantation of the electrodes. The first step of DBS programming is to identify the thresholds to side effects. However, the relationship between lead location and the threshold to adverse effects is not fully understood. Anatomical measurements and electrode location were evaluated on a stereotactic surgical planning software, whereas stimulation parameters and side effects were obtained from medical records. Correlations among these variables were tested using univariate and multivariable analyses. Monopolar stimulation elicited capsular side effects (CSEs) in 208 of 316 contacts (65.8%) and noncapsular side effects (NCSEs) in 223 of 316 contacts (70.6%). The occurrence of CSEs was correlated with contact number (p = 0,009) and with the \"Z\" coordinate (p = 0,03), whereas voltage threshold to CSEs exhibited correlation with the internal capsule angle (p = 0,035). The occurrence of NCSEs was correlated with contact number (p = 0,005), \"X\" (p = 0,03), \"Y\" (p = 0,004), and the distance to the red nucleus (p = 0,001 and p = 0,003). There was correlation between voltage threshold to NCSEs and the internal capsule angle (p = 0,006), electrode\'s coronal angle (p = 0,02), \"X\" (p = 0,001), \"Y\" (p < 0,001), \"Z\" (p < 0,001), and the distances to the internal capsule (p = 0,02) and to the red nucleus (p = 0,004 and p < 0,001). CSEs were associated with more distally contacts, with deeper localization, as well as with greater internal capsule angles. NCSEs were associated with more distally contacts, with localization more medial, posterior and inferior, and closer to the red nucleus. Moreover, there was a correlation between NCSEs and electrodes implanted with greater coronal angles, as well as with greater internal capsule angles. These findings can be useful to inform novel targeting strategies for deep brain stimulation lead implantation.

La maladie de Parkinson est une maladie neurodégénérative secondaire à la mort des neurones dopaminergiques, entraînant un dysfonctionnement des ganglions de la base (GB), ensemble de noyaux sous corticaux impliqués dans le contrôle de la motricité. Les symptômes moteurs sont améliorés par le traitement dopaminergique et par la stimulation cérébrale profonde (SCP) du noyau subthalamique (NST). Il a été montré que le changement d’activité bêta est corrélé avec l’amélioration motrice des symptômes de bradykinésie et rigidité. L’hypothèse serait que les oscillations bêta pourraient être un physiomarqueur spécifique des symptômes moteurs de la MP. L’objectif de cette thèse est de comprendre l’activité du NST et de trouver un physiomarqueur de la MP : au repos et pendant un paradigme Go/Nogo.Dans une première partie, pour 55 patients, nous avons modélisé la puissance avec un modèle linéaire à effets mixtes dans six bandes de fréquences selon la position des électrodes, la présence de complications liées au traitement dopaminergique, de la sévérité des symptômes, et du changement de ces symptômes suite à la prise du traitement dopaminergique. Le changement le plus important entre OFF- et ON-DOPA est observé dans la bande low-bêta. Cependant, nous n’avons pas trouvé de corrélation entre la sévérité de la bradykinésie, rigidité, ou du score axial avec l’activité low-bêta. Mais, nous avons trouvé que la sévérité de la rigidité était associée aux fréquences supérieures à 20Hz. Nous avons également trouvé une corrélation positive entre la sévérité du tremblement dans toutes les bandes de fréquences, qui est très importante pour la bande thêta. Etonnement, nous avons trouvé que les complications liées au traitement dopaminergique pouvaient induire des informations dans toutes les bandes. Cet effet est très important pour la bande thêta. Nos résultats au repos suggèrent que l’activité bêta n’est pas le physiomarqueur idéal de la MP.Pendant le paradigme Go/Nogo, pour 15 patients, nous avons modélisé la puissance avec un modèle linéaire à effets mixtes pour toutes les fréquences selon la position des électrodes, la sévérité des symptômes, les données comportementales et cinétiques. Nous avons trouvé une spécificité temporelle et spatiale des activités du NST au cours du paradigme. Nos résultats montrent que le NST est impliqué dans le contrôle des différentes étapes du mouvement volontaire du membre supérieur et que le défaut de dopamine dans le circuit sensorimoteur des GB génère une série de changements oscillatoires au sein du NST lors du mouvement. Cependant, l'activité thêta est apparue comme une activité caractéristique en OFF-DOPA fortement corrélée aux paramètres comportementaux et cinétiques. Cette activité pourrait être le physiomarqueur de la MP pendant l'exécution d'un mouvement, son augmentation pourrait induire une réponse motrice et un mouvement rapide. / The Parkinson's disease is a secondary neurodegenerative disease in the death of the dopaminergic neurons, pulling a dysfunction of the ganglions of the base (GB), the set pits under cortical implied in the control of the motricity...

Le but de cette étude était d'évaluer le rôle des boucles des ganglions de la base et des voies dopaminergiques sur les mécanismes « bottom-up » et « « top-down » du contrôle de l'attention visuelle (AV). Nous avons comparé les performances sur 3 tâches informatisés, appropriées à l'étude de la capture attentionnelle (CA), des mécanismes de sélection de la réponse motrice et d'initiation du mouvement, de deux groupes de patients avec maladie de Parkinson (MP) - un groupe étant évalué dans trois différentes conditions de stimulation électrique (sans stimulation, ou stimulation sélective de la partie sensorimotrice, SM, ou de la partie associative, AS, du noyau subthalamique, NST), l'autre groupe étant évalué dans deux différentes conditions de traitement médical (avec ou sans levodopa) - avec celles d'un groupe des sujets contrôles. Nos résultats suggèrent dans la MP un affaiblissement des mécanismes « top-down » de contrôle de l'AV, ce qui pourrait aussi expliquer indirectement l'augmentation de la CA. Le traitement dopaminergique est efficace dans le rétablissement des mécanismes « top-down » de l'AV, suggérant une implication des voies dopaminergiques dans ce domaine cognitif. Ces voies semblent aussi jouer un rôle dans les mécanismes « bottom-up » de l'attention, comme l'a suggéré le renforcement de la CA sous traitement dopaminergique. La stimulation du NST a montré un effet similaire à celui obtenu par un traitement dopaminergique, en favour d'une implication directe des boucles des ganglions de la base dans le contrôle de l'AV. Nos résultats ont mis en évidence une spécialisation fonctionnelle de différents sous-territoires du NST en ce qui concerne les mécanismes de « top-down ». La stimulation SM produit des effets marqués sur les processus d'initiation de mouvement et des effets positifs sur les mécanismes endogènes de l'AV, alors que la stimulation de la partie AS semble être plus particulièrement efficace dans l'amélioration des mécanismes de sélection de cible. / We aimed to investigate the possible role of cortico-basal ganglia loops and dopaminergic pathways in the mechanisms of top-down and bottom-up control of visual attention (VA). We compared the performances on 3 computerized tasks, respectively suitable to study attentional capture (AC), motor response selection and movement initiation, of two groups of patients with Parkinson's disease (PD), one evaluated in different sets of electrical stimulation (without stimulation, or selective stimulation of the sensorimotor, SM, or associative, AS, parts of the subthalamic nucleus, STN), the other in different conditions of medication (with or without levodopa), with those of a group of controls. Our results showed that in PD there is a weakening of the mechanisms underlying the top-down control of VA, which also would account indirectly account for the enhancement of AC. Dopaminergic treatment proved to be effective in restoring the top-down mechanisms of VA, suggesting an involvement of dopaminergic pathways in this cognitive domain. These pathways seem to play a role also in the bottom-up mechanisms of attention, as suggested by the enhancement of AC under dopaminergic treatment. The STN-stimulation showed a similar effect to that obtained by dopaminergic treatment, establishing a direct involvement of the basal ganglia loops in VA control. Our results highlighted a functional specialization of different sub-territories of the STN in relation to the top-down mechanisms. SM stimulation produced marked effects on the movement initiation processes and appreciable positive effects on endogenous VA mechanisms, while AS stimulation seems to be especially effective in improving the mechanisms of target selection.

Par sa connectivité directe avec le cortex, le noyau subthalamique (NST) représente une des structures d'entrée du système des ganglions de la base, et se trouve impliqué dans différents aspects du comportement (contrôle moteur, cognitif et limbique). Néanmoins, les corrélats électrophysiologiques de ces processus restent débattus. Les études effectuées dans le cadre de cette thèse visent à éclaircir le rôle possible du NST dans trois fonctions exécutives, à savoir l'inhibition réactive (suppression d'un mouvement programmé), l'inhibition proactive (préparation à inhiber son mouvement) et l'attention soutenue. Pour ce faire, les activités extracellulaires et/ou en potentiels de champs locaux du NST ont été enregistrées chez 28 patients parkinsoniens pendant qu'ils effectuaient des taches cognitives, visant à dissocier les corrélats de ces différentes fonctions exécutives. Dans une première étude, les activités en potentiel de champs locaux du NST lors de l'inhibition réactive et proactive ont été étudiées à l'aide d'un paradigme modifié du « stop signal ». L'inhibition réactive se caractérise par une augmentation rapide de synchronisation relative de l'activité du NST dans la bande de fréquence β (13-35 Hz), tandis que l'inhibition proactive se caractérise par la maintenance tonique d'un niveau élevé d'activité β qui prédit les performances des patients lors de l'inhibition réactive. Dans la seconde étude, nous avons montré qu'une population neuronale (n=7 neurones) augmente rapidement sa fréquence de décharge lors de l'inhibition réactive. Enfin, dans la troisième étude, nous avons utilisé un paradigme permettant de moduler le niveau attentionnel requis pour réaliser un comportement simple. Nos résultats indiquent qu'une baisse d'activité β est observée uniquement lorsque le sujet maintient une attention soutenue pour encoder, retrouver en mémoire une information afin de produire une réponse. L'ensemble de ces résultats nous ont permis d'apporter des preuves électrophysiologiques de l'implication du NST dans ces différentes fonctions et de clarifier la dynamique temporelle des activités neuronales supportant ces processus. Ils suggèrent ainsi l'hypothèse d'une implémentation de différents aspects du contrôle exécutif dans le NST via des mécanismes communs et interactifs dont la dynamique temporelle permettrait la modulation fine du comportement. / The subthalamic nucleus (STN) is an input structure of the basal ganglia implicated in many behavioral processes (motor, cognitive and limbic control). However the electrophysiological correlates of these processes remain unclear. This thesis aims to clarify the role of the STN during 3 executive functions: reactive inhibition (suppression of a prepotent move), proactive inhibition (preparation to inhibit a move) and sustained attention. To this end, extracellular and local field potential activities were recorded in 28 patients with Parkinson's disease while they performed cognitive tasks, aiming to dissociate the neural correlates of these executive functions In a first study, local field potentials β (13-35 Hz) activity was recorded in the STN during reactive and proactive inhibition. Reactive Inhibition was related to a relative increase of β activity, while proactive inhibition was related to maintenance of a tonic level of β activity predictive of reactive inhibitory performances. In a second study, we showed that reactive inhibition is related to a phasic increase of firing rate in a neuronal subpopulation (n=7 neurons). In a third study, we recorded Local field potentials in the STN while patients performed a sustained attention-demanding task (combining a visual search and a delayed match-to-sample paradigm) and found a systematic suppression of 15-35 Hz activity during each repetition of the task directly related to the amount of attention allocated by the participants. Altogether, these results present electrophysiological evidences of the implication of the STN in these functions and clarify the temporal dynamics of neuronal activities supporting these processes. These results may suggest an implementation of various executive functions in the STN via common and interactive mechanisms which temporal dynamics would mediate behavioral control.

Gamma oscillations of local field potentials (LFP) in the basal ganglia and thalamus had not been studied during saccades. Eleven patients were studied during deep brain stimulation (DBS); 6 were in the subthalamic nucleus (STN); 3 in the globus pallidus interna (GPi); and 2 in the thalamic ventralis intermedius nucleus (Vim). Patients performed horizontal saccades to visual targets while LFPs from DBS electrodes, scalp electroencephalogram (EEG), and electrooculogram (EOG) were recorded. Wavelet spectrograms were generated and saccade onset and event-related gamma synchronizations (ERS) were compared to baseline without eye motion. ERS were recorded at and after saccade onset in the STN, GPi and Vim, EEGs and EOGs; but were absent during target light illumination without saccades. ERS were symmetric in all DBS contacts and appeared identical in DBS LFPs, frontal EEGs and EOGs. These findings indicate their origin from extraocular muscle spike potentials rather than brain neural activity.

Gamma oscillations of local field potentials (LFP) in the basal ganglia and thalamus had not been studied during saccades. Eleven patients were studied during deep brain stimulation (DBS); 6 were in the subthalamic nucleus (STN); 3 in the globus pallidus interna (GPi); and 2 in the thalamic ventralis intermedius nucleus (Vim). Patients performed horizontal saccades to visual targets while LFPs from DBS electrodes, scalp electroencephalogram (EEG), and electrooculogram (EOG) were recorded. Wavelet spectrograms were generated and saccade onset and event-related gamma synchronizations (ERS) were compared to baseline without eye motion. ERS were recorded at and after saccade onset in the STN, GPi and Vim, EEGs and EOGs; but were absent during target light illumination without saccades. ERS were symmetric in all DBS contacts and appeared identical in DBS LFPs, frontal EEGs and EOGs. These findings indicate their origin from extraocular muscle spike potentials rather than brain neural activity.

Στην παρούσα εργασία μελετάμε τη μοντελοποίηση του υποθαλαμικού πυρήνα των βασικών γαγγλίων με χρήση του μαθηματικού νευρωνικού μοντέλου Izhikevich. Βάση της μελέτης μας αποτελούν μικροηλεκτροδιακές καταγραφές, που έχουν ληφθεί κατά τη διάρκεια νευροχειρουργικών επεμβάσεων εν τω βάθει εγκεφαλικής διέγερσης, για τη συμπτωματική θεραπεία της νόσου Πάρκινσον. Θα ξεκινήσουμε με μια εισαγωγή στην φυσιολογία του νευρικού κυττάρου και στην ανατομία των βασικών γαγγλίων. Θα αναλύσουμε τα βασικά ποιοτικά μοντέλα που ερμηνεύουν τη συμμετοχή των τελευταίων σε κινητικές διεργασίες, αλλά και την εμπλοκή τους στη νόσο Πάρκινσον. Μετά από μια σύντομη αναφορά στη μέθοδο της εν τω βάθει διέγερσης και στις μικροηλεκτροδιακές καταγραφές, θα εστιάσουμε στα δυναμικά τοπικού πεδίου και στη νευροφυσιολογική σημασία τους. Συνεχίζοντας, θα κάνουμε μια περιεκτική ανασκόπηση των βασικότερων μαθηματικών μοντέλων νευρώνων και ύστερα θα επικεντρωθούμε στον υποθαλαμικό πυρήνα, περιγράφοντας δύο πρόσφατα μοντέλα που έχουν κατασκευαστεί για την προσομοίωση των νευρώνων αυτού. Έπειτα, θα περάσουμε στην περιγραφή του μοντέλου Izhikevich και στην τροποποίησή του για την αναπαραγωγή των χαρακτηριστικών του νευρώνα του υποθαλαμικού πυρήνα. Κατόπιν, θα αναλύσουμε τη μεθοδολογία που ακολουθήσαμε στην παρούσα υλοποίηση και τις βασικές θεωρήσεις της μοντελοποίησης μας. Θα ολοκληρώσουμε με την παρουσίαση των αποτελεσμάτων, το σχολιασμό αυτών και τις ιδέες για μελλοντική επέκταση της μεθόδου μας. / The main objective of this MSc thesis is the study of subthalamic nucleus, by using the Izhikevich neuron model. Microelectrode recordings, taken during deep brain stimulation operations for Parkinson’s disease, have been used for that purpose. In chapters 1-2, there is an introduction to the physiology of the neuron and the basal ganglia anatomy. In the two following chapters, we are analyzing the basic qualitative models that describe the involvement of the basal ganglia in movements and the pathophysiology of Parkinson’s disease. We are briefly discussing the method of deep brain stimulation, microelectrode recordings processing and the extraction of local field potentials. In chapter 5, the basic mathematical neuron models are discussed. We are focusing on the subthalamic nucleus and we are describing two recently developed mathematical models of the subthalamic neuron. In chapter 6, we are outlining Izhikevich neuron model and its modification in order to describe the subthalamic neuron. In addition, we are analyzing the methodology developed for the implementation of the modeling process and our basic considerations. In chapter 7, the results of the simulation are presented and discussed, so that our conclusions provide ideas for further research.

Σκοπός της μελέτης : H διερεύνηση της επίδρασης του εν τω βάθει εγκεφαλικού ερεθισμού στον υποθαλάμιο πυρήνα (STN-DBS) στη λειτουργία του Αυτόνομου Νευρικού Συστήματος (ΑΝΣ) σε ασθενείς με Νόσο Πάρκινσον. Μέθοδος-Υλικό: Στη μελέτη έλαβαν μέρος 24 ασθενείς με ιδιοπαθή νόσο Πάρκινσον και 24 υγιείς μάρτυρες με πλήρη αντιστοιχία ως προς το φύλο και την ηλικία (μέσος όρος ηλικίας± σταθερά απόκλιση, 62.1±9.4 έτη). Η εκτίμηση των ασθενών έγινε 3 μέρες προ χειρουργείου ενώ ελάμβαναν κανονικά την αγωγή τους και 6 μήνες μετά την επέμβαση σε “on DBS/ on medication” κατάσταση. Όλοι οι ασθενείς συμπλήρωσαν ένα ερωτηματολόγιο σχετικά με τα συμπτώματα από το ΑΝΣ και υπεβλήθησαν σε μέτρηση της Αρτηριακής Πίεσης (ΑΠ) σε ύπτια θέση καθώς και στο 1ο και 3ο λεπτό μετά από απότομη έγερση από ύπτια σε όρθια θέση. Η νευροφυσιολογική εκτίμηση ασθενών και μαρτύρων περιελάμβανε: α. μέτρηση της συμπαθητικής δερματικής απάντησης (ΣΔΑ) από την παλάμη και το πέλμα με ηλεκτρικό ερεθισμό, β. μελέτη της διακύμανσης του καρδιακού ρυθμού (ΚΡ) ως προς τον χρόνο στις φάσεις της ήρεμης και βαθιάς αναπνοής (Rest RR IV και DB RR IV), κατά τη δοκιμασία Valsalva (Valsalva ratio) και κατά το Τilt-test (Tilt ratio). Με τη φασματική ανάλυση της πεντάλεπτης καταγραφής του ΚΡ σε ηρεμία που πραγματοποιήθηκε αργότερα υπολογίστηκαν οι παράμετροι LF, HF, LFnorm, HF norm, TP και ο λόγος LF/HF. Αποτελέσματα: Το 45,8% των ασθενών είχαν ορθοστατική υπόταση πριν και 12,5% μετά την επέμβαση, αλλά κατά τη στατιστική ανάλυση των μετρήσεων αυτών δεν πρόεκυψε σημαντική διαφορά μεταξύ των δύο ομάδων. Βρέθηκε σημαντική μείωση της συχνότητας των διαταραχών εφίδρωσης, της ακράτειας και της δυσκοιλιότητας στην μετεγχειρητική εκτίμηση (p<0,005). Στη ΣΔΑ μεταξύ των ασθενών πριν και μετά το STN-DBS δε βρέθηκαν στατιστικά σημαντικές διαφορές. Συνολικά 6 ασθενείς είχαν παθολογική ή απούσα ΣΔΑ πριν το χειρουργείο και 7 μετά (χ 2, p=0,114). Στις παραμέτρους Rest RR IV, DB RR IV, Valsalva ratio & Tilt ratio δε διαπιστώθηκε σημαντική διαφορά προ και μετά DBS (p>0.,050) και ήταν μάλιστα και προ- και μετεγχειρητικά μειωμένες στους ασθενείς απ’ ότι στους μάρτυρες (p <0,050). Σημαντική μείωση μόνο της παραμέτρου LF προέκυψε συγκρίνοντας τους ασθενείς πριν και μετά τη χειρουργική επέμβαση ενώ οι ασθενείς μετεγχειρητικά είχαν σημαντικά μειωμένες τιμές των LF, TP και LFnorm σε σχέση με τις αντίστοιχες τιμές των υγιών μαρτύρων. Δε βρέθηκε συσχέτιση (p >0,050) της κινητικής βελτίωσης λόγω DBS με τις ατομικές διαφορές των τιμών των παραμέτρων στον εκάστοτε ασθενή πριν και μετά το χειρουργείο. Συμπεράσματα: Είναι σαφής η θετική επίδραση του DBS στη μείωση της συχνότητας των διαταραχών εφίδρωσης, αλλά το χειρουργείο δεν έπαιξε αξιοσημείωτο ρόλο στις ΣΔΑ. Βρέθηκε μόνο μια μη στατιστικά σημαντική μείωση του ποσοστού των ασθενών με Ο.Υ., ενώ καμία επίδραση δεν υπήρξε στις παθολογικές τιμές του Κ.Ρ. των ασθενών. H φασματική ανάλυση του Καρδιακού Ρυθμού δεν έδειξε αλλαγή στην ισορροπία μεταξύ συμπαθητικής και παρασυμπαθητικής λειτουργίας λόγω DBS. Γενικό συμπέρασμα είναι ότι STN-DBS ωφελεί σημαντικά την κινητική βελτίωση, αλλά δεν έχει αξιόλογη, θετική ή αρνητική, επίδραση στη ρύθμιση της λειτουργίας του ΑΝΣ. / Purpose: To assess the impact of subthalamic nucleus (STN) deep brain stimulation (DBS) on the autonomic nervous system function in patients with advanced Parkinson’s disease (PD). Material- Methods: Twenty-four patients with idiopathic PD (mean age±SD, 62.1±9.4 years old) were examined 3 days before and 6 months after DBS, “on medication” state both times. Each examination session included registration of autonomic symptoms by means of a semi-structural questionnaire, blood pressure (BP) recording at supine position and at the first and third minute after sudden change from supine to standing position and a neurophysiological assessment. The neurophysiological examination included: a. recording of sympathetic skin response (SSR) from both palms and a sole, b. time domain analysis of RR interval variation during normal and deep breathing, during Valsalva manoeuvre and during tilt test. By off-line performed frequency domain analysis of heart rate variation the Total Power, the Low Frequency band, the High Frequency band and their normalized units were estimated. The neurophysiological measurements were compared to those of 24 healthy controls matched for age and sex. Results: Orthostatic hypotension was present in 45.8% of the patients preoperatively and 12.5% postoperatively, whereas statistical analysis showed no significant difference in BP measurements between pre- and post DBS studies. A statistical significant reduction in the frequency of autonomic symptoms such as constipation, sweating disturbances and urgency was established after implantation. In SSR measurements no change was found between patients before and after DBS. Six out of 24 patients has abnormal or absent SSR before surgery and 7 afterwards (χ 2, p =0.114). The values of time domain variables were both pre and postoperatively lower in patients than in controls. A significant reduction was found in LF band after the implantation. There was no correlation between individual, deep brain stimulation-related changes of motor function and corresponding neurophysiological measurements. Conclusions: The positive effect of STN-DBS on the sweating disturbances reported by patients is established, whereas no influence was found on SSR measurements. Subthalamic stimulation had no effect on the abnormal heart rate regulation of the patients, but a non significant reduction in orthostatic hypotension was noticed. Finally through spectral analysis no effect on the balance of sympathetic and parasympathetic function was found. Overall, despite its clear benefit on motor performance, STN-DBS had no considerable, positive or negative, impact on the autonomic regulation.

1 Abstract Body weight changes have been described in the course of Parkinson's disease (PD) as well as following bilateral deep brain stimulation of the subthalamic nucleus (STN DBS) performed in advanced PD. According to the literature weight changes occur in 50-100% of patients who undergo STN DBS. In the last 15 years extensive efforts have been put in understanding the underlying mechanisms behind the weight changes following STN DBS in advanced PD patients however many sources still report conflicting evidence. Improved motor status, reduction in dyskinesias, decrease in energy expenditure, dopaminergic medication reduction, modification of food intake, hormonal factors, regional effects of stimulation were all speculated to cause this weight gain. We hypothesized that patients who underwent STN DBS procedure in our center would gain weight as reported in the literature (study 1, study 2). The etiology of post STN DBS weight gain has not been fully elucidated up to date, in our second study we further hypothesized that the weight changes are due to dysregulation of food related hormones and parameters (study 2). In the third study we hypothesized that weight gain is associated with position of active electrode contact (study 3). Aims of the study: The primary aims of our studies were to assess body...