La sclérose en plaques est la maladie non tumorale du système nerveux la plus fréquente du sujet jeune. Elle est définie comme une atteinte démyélinisante inflammatoire multifocale et chronique de la substance blanche du système nerveux central d’origine dysimmunitaire. Le handicap moteur est l’un des risques évolutifs principaux de cette maladie. Mieux caractériser les mécanismes du dysfonctionnement du système moteur (atteinte de la voie motrice centrale efférente, altération du réseau moteur cortical à l’origine du mouvement) de même que les mécanismes compensatoires qui le limitent est un enjeu important dans la compréhension et la prévention de l’apparition du handicap. L’étude de ces mécanismes au stade précoce de la maladie permet de mieux comprendre les liens entre l’atteinte tissulaire, les mécanismes de compensation et les conséquences fonctionnelles. Nos travaux ont permis au stade précoce de la SEP de mieux caractériser l’atteinte fonctionnelle de la voie motrice centrale, de montrer l’influence de l’atteinte encéphalique diffuse sur la réorganisation corticale du système moteur et enfin de démontrer l’existence d’une plasticité cérébrale fonctionnelle basale du réseau moteur non dominant corrélée avec les changements d’activation observés lors du mouvement au sein du même réseau. / Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system which is frequently responsible for motor disability. Better assessment of pathophysiological process implicated in motor system dysfunction (cortico-spinal tract or more diffuse tissue damage) as well as the compensatory mechanises are critical in the understanding and the prevention of disability. Their study in the early stage of the disease will allow to a better understanding of the links between tissue injury, compensatory mechanisms and functional consequences. We have better characterized functional dysfunction of the central motor pathway at the early stage of multiple sclerosis. We have also evidenced the influence of diffuse brain injury on functional motor cortical reorganization. Last, we have demonstrated the existence of a basal functional plasticity at rest of the nondominant motor network that is correlated with its functional plasticity during action.

Introdução e objetivos: Estudos recentes sugerem que a estimulação magnética transcraniana repetitiva (EMTr) aplicada sobre o córtex motor é eficaz no tratamento analgésico de doentes com dor crônica. O objetivo deste estudo foi avaliar os efeitos da aplicação da EMTr sobre o córtex motor, utilizada como co-intervenção terapêutica no tratamento de pacientes com síndrome complexa de dor regional (SCDR) refratária aos tratamentos convencionais. Métodos: Vinte e três doentes com SCDR na mão foram distribuídos aleatoriamente em dois grupos de tratamentos para receberem o tratamento padrão (analgésicos, medicações adjuvantes e terapia física) associado a dez sessões diárias e consecutivas de EMTr rápida ou estimulação magnética placebo (EMTp), aplicadas sobre a região correspondente ao córtex motor da mão acometida. Os grupos foram comparados em relação aos aspectos epidemiológicos, apresentação clínica da doença, intensidade da dor, alterações do humor, qualidade de vida e função do membro acometido até noventa dias após a conclusão do tratamento, utilizando-se de entrevistas estruturadas, da escala visual analógicas de dor (EVA), do questionário de dor de McGuill (QM), do questionário PIQ-6 (Pain Inpact Questionnaire), do questionário DASH (Disabilities of Arm, Shoulder and Hand), do questionário SF-36 e dos questionários Hamilton para ansiedade e depressão. Resultados: Ocorreu redução significativa dos escores da EVA no grupo tratado com EMTr durante o tratamento, que durou até o sétimo dia após o encerramento das aplicações (p<0.05). A redução média da EVA no grupo tratado com EMTr foi de 4.65 cm (redução de 50.9% dos escores de dor), estatisticamente superior ao grupo tratado com placebo, no qual a redução foi de 2.18 cm (redução de 24.7%). A diminuição dos escores de dor na EVA foi independente de outras variáveis em estudo, exceto pela melhora no domínio sete do questionário SF-36 (aspectos emocionais). Conclusões: A aplicação de EMTr rápida sobre a área motora da mão de doentes com SCDR, associada a um programa de tratamento padrão, resulta em diminuição maior da percepção espontânea da dor quando comparada ao efeito do tratamento padrão isolado, independentemente de outros possíveis efeitos da EMTr sobre o humor, função do membro acometido ou qualidade de vida / Background and aims: There are many evidences that repetitive transcranial magnetic stimulation (r-TMS) of the motor cortex is effective in relief of chronic pain. The aim of this study was to evaluate the analgesic effects of r-TMS in patients with refractory CRPS. Methods: Twenty-three patients presenting with complex regional pain syndrome (CRPS) of the hand were randomly selected and treated with conventional treatment (analgesics, adjuvant medications and physical therapy) plus sham-TMS or r-TMS to the motor cortex opposite the affected limb: 100% MT, 10 hz, 10 s trains, 25 trains daily, 10 daily sessions. The Visual Analogical Scale of Pain (VAS), McGill Questionnaire, Pain Impact Questionnaire (PIQ-6), Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH), Hamilton Depression and Anxiety Rating Scales and SF-36 Questionnaire were the instruments used for the evaluation. The groups were comparable with regards to socio-demographics, mood and pain intensity. Evaluations were performed before, during TMS treatment and up to three months the end of the treatment. Results: There was a significant reduction in VAS scores favoring the r-TMS group up to the seventh follow-up day (p <0.05). The mean reduction in the rTMS group was of 4.65 cm (fall of 50.9%) against 2.18 cm (fall of 24.7%) in sham group during treatment. Improvement in VAS scores was independent of other variables, except for improvement in emotional aspects in the SF-36. Conclusions: During r-TMS sessions there was significant and positive improvement in pain experience of CRPS patients regardless of mood, function or quality of life effects

La faiblesse des muscles périphériques, définie par une diminution de la force maximale volontaire en dehors de tout état de fatigue neuromusculaire, est une complication fréquente de la broncho-pneumopathie chronique obstructive (BPCO). La force maximale volontaire dépend à la fois des propriétés musculaires périphériques (i.e. volume et architecture musculaire, qualités contractiles) et de la capacité du système nerveux à activer le muscle maximalement. Dans la BPCO, plusieurs travaux ont souligné l'existence paradoxale d'une perte de force maximale volontaire sans altérations musculaires périphériques et sans qu'un déficit d'activation volontaire n'ait clairement été identifié. Pourtant, les patients atteints de BPCO présentent de nombreuses altérations du système nerveux, compatibles avec une capacité d'activation volontaire altérée.L'objectif de ce travail de thèse était donc de tester l'implication du système nerveux dans la faiblesse musculaire de la BPCO et d'en déterminer les mécanismes sous-jacents. Au cours de nos travaux, nous avons mis en évidence une activité corticale diminuée dans la BPCO lors de contractions maximales et sous-maximales volontaires. Nous avons par ailleurs rapporté une perte d'excitabilité du cortex moteur et un déficit d'activation volontaire spécifique aux patients atteints de faiblesse musculaire. Ces résultats sont en accord avec une implication des altérations cérébrales dans la faiblesse musculaire périphérique de la BPCO. Nous sommes ensuite parvenus à identifier une origine potentielle des altérations cérébrales : les désaturations en O2 au cours du sommeil avec mouvements non-rapides des yeux (NREM). Cette hypothèse a été corroborée par l'observation d'un niveau d'activation volontaire réduit chez les patients désatureurs en sommeil NREM. En revanche, aucune répercussion significative n'a pu être observée sur la force maximale volontaire de ces patients, suggérant l'existence d'un mécanisme compensatoire. In fine, nos résultats constituent une avancée importante dans la compréhension du phénomène de faiblesse musculaire, classiquement attribué à la seule perte de masse musculaire. L'implication du système nerveux central dans la faiblesse musculaire ouvre notamment la voie à de nouvelles modalités de prise en charge par des approches spécifiques, dans l'optique de lutter contre la faiblesse musculaire et ses multiples répercussions négatives dans la vie du patient atteint de BPCO. / Peripheral muscle weakness, as defined by a reduced voluntary strength outside any state of neuromuscular fatigue, is a common complication of chronic obstructive pulmonary disease (COPD). Maximal voluntary strength is determined by both peripheral muscle properties (i.e. muscle volume and architecture, contractile quality) and the nervous system's ability to activate the muscle maximally. In COPD, many studies highlighted the paradoxical existence of maximal voluntary strength loss without any peripheral muscle impairment, and without a clearly identified voluntary activation deficit. However, patients with COPD exhibited several nervous system alterations compatible with a reduced maximal voluntary activation capacity. The aim of this thesis was to test the nervous system implication in COPD muscle weakness and to determine the involved mechanisms. As major results, we found a reduced cortical activity in COPD during maximal and sub-maximal voluntary contractions. Furthermore, we reported reduced motor cortex excitability and voluntary activation deficit, specifically in patients with muscle weakness. These results are in accordance with an involvement of cortical alterations in COPD muscle weakness. Then, we indentified a potential origin for cortical alterations: O2 desaturation during non-rapid eye movement (NREM) sleep. This hypothesis has been corroborated by the observation of a reduced voluntary activation in patients with NREM sleep desaturation. However, no significant repercussion could have been observed on maximal voluntary strength in these patients, suggesting a compensatory mechanism.Our results are an important step forward in understanding the COPD muscle weakness that was classically attributed to loss of muscle mass only. The involvement of the central nervous system in COPD muscle weakness also brings about new patient care opportunities via tailored approaches, in order to fight against muscle weakness and its deleterious consequences on a patient's life.

Introdução e objetivos: Estudos recentes sugerem que a estimulação magnética transcraniana repetitiva (EMTr) aplicada sobre o córtex motor é eficaz no tratamento analgésico de doentes com dor crônica. O objetivo deste estudo foi avaliar os efeitos da aplicação da EMTr sobre o córtex motor, utilizada como co-intervenção terapêutica no tratamento de pacientes com síndrome complexa de dor regional (SCDR) refratária aos tratamentos convencionais. Métodos: Vinte e três doentes com SCDR na mão foram distribuídos aleatoriamente em dois grupos de tratamentos para receberem o tratamento padrão (analgésicos, medicações adjuvantes e terapia física) associado a dez sessões diárias e consecutivas de EMTr rápida ou estimulação magnética placebo (EMTp), aplicadas sobre a região correspondente ao córtex motor da mão acometida. Os grupos foram comparados em relação aos aspectos epidemiológicos, apresentação clínica da doença, intensidade da dor, alterações do humor, qualidade de vida e função do membro acometido até noventa dias após a conclusão do tratamento, utilizando-se de entrevistas estruturadas, da escala visual analógicas de dor (EVA), do questionário de dor de McGuill (QM), do questionário PIQ-6 (Pain Inpact Questionnaire), do questionário DASH (Disabilities of Arm, Shoulder and Hand), do questionário SF-36 e dos questionários Hamilton para ansiedade e depressão. Resultados: Ocorreu redução significativa dos escores da EVA no grupo tratado com EMTr durante o tratamento, que durou até o sétimo dia após o encerramento das aplicações (p<0.05). A redução média da EVA no grupo tratado com EMTr foi de 4.65 cm (redução de 50.9% dos escores de dor), estatisticamente superior ao grupo tratado com placebo, no qual a redução foi de 2.18 cm (redução de 24.7%). A diminuição dos escores de dor na EVA foi independente de outras variáveis em estudo, exceto pela melhora no domínio sete do questionário SF-36 (aspectos emocionais). Conclusões: A aplicação de EMTr rápida sobre a área motora da mão de doentes com SCDR, associada a um programa de tratamento padrão, resulta em diminuição maior da percepção espontânea da dor quando comparada ao efeito do tratamento padrão isolado, independentemente de outros possíveis efeitos da EMTr sobre o humor, função do membro acometido ou qualidade de vida / Background and aims: There are many evidences that repetitive transcranial magnetic stimulation (r-TMS) of the motor cortex is effective in relief of chronic pain. The aim of this study was to evaluate the analgesic effects of r-TMS in patients with refractory CRPS. Methods: Twenty-three patients presenting with complex regional pain syndrome (CRPS) of the hand were randomly selected and treated with conventional treatment (analgesics, adjuvant medications and physical therapy) plus sham-TMS or r-TMS to the motor cortex opposite the affected limb: 100% MT, 10 hz, 10 s trains, 25 trains daily, 10 daily sessions. The Visual Analogical Scale of Pain (VAS), McGill Questionnaire, Pain Impact Questionnaire (PIQ-6), Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH), Hamilton Depression and Anxiety Rating Scales and SF-36 Questionnaire were the instruments used for the evaluation. The groups were comparable with regards to socio-demographics, mood and pain intensity. Evaluations were performed before, during TMS treatment and up to three months the end of the treatment. Results: There was a significant reduction in VAS scores favoring the r-TMS group up to the seventh follow-up day (p <0.05). The mean reduction in the rTMS group was of 4.65 cm (fall of 50.9%) against 2.18 cm (fall of 24.7%) in sham group during treatment. Improvement in VAS scores was independent of other variables, except for improvement in emotional aspects in the SF-36. Conclusions: During r-TMS sessions there was significant and positive improvement in pain experience of CRPS patients regardless of mood, function or quality of life effects