La paralysie cérébrale (PC) regroupe un ensemble varié de troubles moteurs, sensoriels et cognitifs, liés à des lésions de la substance blanche (i.e. leucomalacie périventriculaire, PVL) survenant, le plus souvent, après un épisode hypoxo-ischémique autour de la naissance. Afin de reproduire la PVL chez l'animal, nous utilisons une ischémie prénatale (PI) qui induit des lésions des substances blanche et grise. Les rats ischémiés développent des déficits cognitifs visuo-spatiaux et une hyperactivité, également observés chez les patients atteints de PC, liés à des lésions du cortex entorhinal, préfrontal et cingulaire. La PI n'induit que des troubles locomoteurs modérés associés à des signes de spasticité, et une atteinte anatomique et fonctionnelle du cortex somesthésique primaire (S1), tandis que le cortex moteur (M1) reste intact. Ainsi, la PI reproduit les symptômes observés chez les enfants et adultes nés prématurément. La présence de mouvements spontanés anormaux au cours de la 1ère année conduisant à la PC suggère une implication de l'expérience sensorimotrice anormale dans le développement de cette pathologie. La combinaison d'une restriction sensorimotrice (SMR) durant le développement et de la PI induit des troubles cognitifs atténués mais une hyperactivité importante. Les rats combinant PI et SMR présentent des déficits posturo-moteurs drastiques et une spasticité, associés à une dégradation des tissus musculo-squelettiques, comparables à ceux observés chez les patients. Ces troubles moteurs, associés à une désorganisation importante des cartes corticales dans S1 et M1, suggèrent un dysfonctionnement important des boucles d'intégration sensorimotrice. / Cerebral palsy (CP) corresponds to various motor, sensory and cognitive disorders related to white matter damage (i.e. periventricular leucomalacia, PVL) often occurring after perinatal hypoxic-ischemic events. To reproduce PVL in rodents, we used a prenatal ischemia (PI) that induces white and gray matter damage. The ischemic rats exhibit visual-spatial cognitive deficits and hyperactivity, as observed in patients with CP, related to lesions of entorhinal, prefrontal and cingular cortices. Only mild locomotor disorders are induced by PI, associated to signs of spasticity, along with anatomical and functional degradation in the primary somatosensory cortex (S1), while the primary motor cortex (M1) remains unchanged. Thus, PI recapitulates the main symptoms found in children born preterm. Abnormal spontaneous movements (i.e. general movements) observed in infants who develop CP later on suggest that abnormal sensorimotor experience during maturation is key in the development of this catastrophic disease. The combination of a sensorimotor restriction (SMR) and PI in animal induces fewer cognitive deficits but still hyperactivity. Such a combination leads to severe postural and motor disorders, and spasticity, associated with musculoskeletal pathologies, as observed in patients with CP. In addition to motor disorders, drastic topographical disorganization of cortical maps in S1 and M1 suggest a major dysfunction of sensorimotor loops.

O objetivo deste estudo foi avaliar o efeito do biofeedback (BIO) associado à terapia ocupacional (TO) e à estimulação elétrica funcional (FES) na espasticidade, movimento ativo e função do membro superior de pacientes hemiplégicos. Este estudo foi realizado na Divisão de Medicina de Reabilitação do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Cinqüenta e nove pacientes acometidos por acidente vascular cerebral participaram do estudo por um ano; 31 receberam TO+FES duas vezes por semana + BIO uma vez por semana e 28 receberam somente TO+FES duas vezes por semana. Os pacientes foram avaliados inicialmente, após 6 meses e após 1 ano através da Avaliação da Função Manual, do Teste de Destreza Manual Minnesota, do Teste de Amplitude de Movimento e da Escala de Ashworth modificada. TO+FES+BIO melhoraram significativamente a amplitude de movimento e função dos membros superiores após 6 meses e 12 meses, quando comparado com somente TO+FES. Ambos os grupos melhoraram significativamente a espasticidade, após 6 meses e 12 meses, com diferença não significante entre eles. O uso adicional do biofeedback mostrou efeito positivo em amplitude de movimento e recuperação da função do membro superior no grupo estudado e pode representar uma importante ferramenta para a reabiltação de pacientes hemiplégicos / The objective of this was to study the effect of biofeedback (BIO) associated to occupational therapy (OT) and functional electrical stimulation (FES) on spasticity, range of motion and upper extremity function of hemiplegic patients. The study took part at the Division of Rehabilitation Medicine of the Hospital das Clínicas of the University of São Paulo School of Medicine. Fifty-nine stroke patients were studied for one year; 31 received OT+FES twice a week + BIO once-a-week and 28 received only OT+FES twice-aweek. The patients were evaluated initially, after six months and after one year with the use of Manual Function Evaluation, Minnesota Manual Dexterity Test, Range of Joint Motion Test and Modified Ashworth Scale. OT+FES+BIO significantly improved range of motion and upper extremity function after 6 months and 12 months, compared to only OT+FES. Both groups showed significant improvement of spasticity, after 6 months and 12 months, with no significant difference between them. The additional use of BIO had a positive effect in range of motion and function recovery of upper extremity in the studied group and may represent an important therapeutic tool for stroke rehabilitation

Foi comparada a massa óssea e a composição corporal dos hemicorpos dominante e não dominante de um grupo (A) de 16 pessoas com paralisia cerebral com hemiplegia espástica, e de um grupo (B) de 29 voluntários normais por meio da mensuração da massa corporal, estatura e densitometria óssea do corpo total com composição corporal. Foi encontrada diferença estatística significante no conteúdo mineral ósseo dos membros superiores do grupo A e dos membros superiores e inferiores, tronco e total do grupo B; na massa magra dos membros inferiores do grupo A e dos membros superiores e inferiores, tronco e total do grupo B; na massa adiposa dos membros inferiores do grupo A e dos membros superiores e inferiores, tronco e total do grupo B; e no conteúdo mineral ósseo dos membros superiores e inferiores, e total e na massa magra dos membros superiores e inferiores entre os hemicorpos não dominantes dos grupos A e B. Foi encontrada também correlação estatística significante entre o conteúdo mineral ósseo e a massa magra nos grupos A e B em todos os sítios, exceto no tronco dominante do grupo A; e o conteúdo mineral ósseo e a massa corpórea no tronco dominante do grupo A e no membro inferior dominante e bilateral do grupo B / Were compared the bone mass and body composition of the dominant and nondominant hemi bodies in a group (A) of a 16 spastic hemiplegic cerebral palsy and in a group (B) of 27 normal volunteers by weight, height, and densitometry of total body with body composition measure. Were observed significant statistical difference in the bone content mineral of the upper limbs of the group A and of the upper and lower limbs, trunk and total of the group B; in the lean mass of the lower limbs of the group A and of the upper and lower limbs, trunk and total of the group B; in the mass fat of the lower limbs of the group A and of the upper and lower limbs, trunk and total of the group B; and in the bone mineral content of the upper and lower limbs, and total, and in the lean mass of the upper and lower limbs between the hemi bodies no dominant of the A and B groups. Were observed too statistical correlation between the bone mineral content and lean mass in the groups A and B in all locals, except in the trunk of group A; and between the bone mineral content and body mass in the trunk of group A and lower limb dominant and bilateral of group B

Title: Measurement of lower extremities spasticity in patients with cerebral palsy Objectives: The aim of the theoretical part of this thesis is to evaluate possibilities of lower extremities spasticity measurement in adult patients with cerebral palsy. The main focus was given to the concept of French professor J.-M. Gracies: Five- step clinical assessment in spastic paresis. This unique concept presents differentiation of three main factors of motor impairment that emerge as a result of a lesion to central motor pathways: stretch sensitive paresis, soft tissue contracture and muscle overactivity. Ability to distinguish these factors is crucial for specific treatment indication. Finding a correlation between the Five-step clinical assessment in spastic paresis and muscle activity in gait measured with polyEMG was the main objective in the practical part of the thesis. Methodology: This thesis has a theoretical-empirical character. The theoretical part is in a form of a research on the topic of spasticity diagnosis, focused on cerebral palsy patients. The empirical part of the thesis has a form of pilot quantitative research, which was attended by 6 participants with cerebral palsy (4 men and 2 women; average age 29 years). There were 2 independent measurement made for each of them. Each...

Les ataxies héréditaires sont des désordres neuro-dégénératifs qui causent une ataxie comme symptôme primaire; soit une perte de coordination des mouvements volontaires, un sens de l’équilibre déficient et un trouble à la motricité. Elles forment un groupe cliniquement et génétiquement hétérogène. De ce fait, de nombreuses classifications existent basées sur différents critères. Cependant, le consensus actuel veut que le mode de transmission soit le critère premier de classement. On estime la prévalence mondiale des ataxies héréditaires à 6/100 000 bien que ce nombre diffère entre régions. C’est le cas du Québec où la structuration historique du bassin génétique canadien-français a menée à des effets fondateurs régionaux, ce qui a eu comme conséquence de hausser la prévalence régionale de certaines maladies. L’Acadie est également une région canadienne-française avec des effets fondateurs où le taux de prévalence de certaines ataxies héréditaires est plus élevé. Nous avons recruté huit familles canadiennes-françaises provenant de diverses régions du Québec, ayant un lien génétique plus ou moins rapproché avec l’Acadie, dans lesquelles nous avons observé dix cas d’une forme d’ataxie spastique autosomique récessive relativement légère qui a résistée à l’analyse des gènes d’ataxies connues. Nous avons émis l’hypothèse d’être en présence d’une nouvelle forme d’ataxie à effet fondateur pour la population canadienne-française. Afin d’identifier le gène muté responsable de cette ataxie, un criblage génomique des marqueurs SNP pour les individus recrutés fut effectué. Puis, par cartographie de l’homozygotie, une région de 2,5 Mb fut identifiée sur le chromosome 17p13 dans une famille. Une revue de la littérature nous a permis de constater, qu’en 2007, quatre familles nord-africaines atteintes d’une ataxie dénommée SPAX2 qui présentaient des manifestations cliniques semblables avaient déjà été liées au même locus sur le chromosome 17. Afin de supporter notre hypothèse que les malades étaient porteurs de deux copies de la même mutation fondatrice et de cartographier plus finement notre région d’intérêt, les haplotypes de tous les atteints de nos huit familles furent étudiés. Nous avons établie qu’un intervalle de 200 kb (70 SNP), soit du marqueur rs9900036 à rs7222052, était partagé par tous nos participants. Les deux gènes les plus prometteurs des 18 se trouvant dans la région furent séquencés. Aucune mutation ne fut trouvée dans les gènes SLC25A11 et KIF1C. Par la suite, une analyse de liaison génétique stricte avec calcul de LOD score nous a permis d’exclure ce locus de 200 kb comme étant celui porteur du gène muté causant l’ataxie dans la majorité de nos familles. Nous avons donc conclus que malgré qu’une famille soit homozygote pour une grande région du chromosome 17, l’absence d’Informativité des marqueurs SNP dans la région de 200 kb fut responsable de l’apparent partage d’haplotype homozygote. Le travail reste donc entier afin d’identifier les mutations géniques responsables de la présentation ataxique chez nos participants de souche acadienne. / Hereditary ataxias are neurodegenerative disorders which share ataxia as common feature is manifested by a decrease in limb coordination, imbalance and an unsteady gait. They consist in a clinically and genetically heterogeneous group. Many ataxia classifications have been proposed, however, the current consensus is to first characterize them according to their mode of transmission. Hereditary ataxias as a whole have a prevalence of 6/100 000, with variable estimation between country and region. In the Province of Quebec where the French Canadian genetic pool can be seen has a mosaic of regional gene pools there is clear differences in local variation in the prevalence of different ataxias. Acadia is also a French Canadian region with a history of many founder effects and a higher prevalence for certain hereditary ataxias. We recruit 8 French Canadian families from Quebec and with genealogical links with Acadia in which 10 cases manifest a presumably relatively mild autosomal recessive spastic ataxia of unknown etiology. The shared phenotype and Acadian background raised the possibility that they suffered from a new form of ataxia with a founder effect. To identify the mutated gene causing this ataxia, the individuals recruited were genotyped. By homozygosity mapping, a region of 2,5 Mb was identified in one family on chromosome 17p13. A literature review established that in 2007 four North Africans families segregating also a mild spastic ataxia were linked to the same locus on chromosome 17. To support our hypothesis that our patients were carrier of the same founder mutation we look closer at their haplotype in the region. We defined an interval of 200kb (70 SNP) between markers rs9900036 and rs7222052 shared by all affected cases. The two most promising gene in the interval were sequenced. No mutation was found in SLC25A11 and KIF1C. Thereafter a linkage analysis by LOD score excluded the candidate interval of 200 kb in the majority of our families. We conclude that even if in one family exists a large homozygous region on chromosome 17, the lack of informative SNP in the 200 kb region was responsible for the apparent sharing rather than they shared a common mutation. Further work will be necessary to identify the mutate gene causing the ataxia presentation in these cases of mild spastic ataxia.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / A espasticidade é observada na maioria dos pacientes após Acidente Vascular Encefálico (AVE), e exercem influência na presença de deficiências e incapacidades, comprometendo a função motora. As estratégias de neuroreabilitação, o biofeedback eletromiográfico (EMG), têm sido utilizado com aceitação na comunidade médica para reajustes nas habilidades sensório-motoras como retreinamento motor, redução da espasticidade e/ou treinamento de relaxamento. A intervenção ainda apresenta evidências delimitadas quanto a sua efetividade na reabilitação, principalmente, quanto a interferência sobre a atividade cortical e na redução dos sinais espásticos que oferece características negativas na execução do movimento. O objetivo dessa pesquisa foi analisar a possível interferência do treino com biofeedback eletromiográfico sobre a conscientização do controle motor no membro espástico e a caracterização da atividade das bandas de baixa frequência em diferentes regiões corticais orientada pela técnica de treinamento. Dezesseis voluntários acometidos por AVE isquêmicos foram selecionados e divididos em dois grupos (n=8). Grupo experimental (GE) submetidos ao treino com biofeedback associado a fisioterapia, e o grupo controle (GC) submetido apenas à fisioterapia convencional. Foi realizada a avaliação do grau de espasticidade pelo limiar de reflexo do estiramento tônico (LRET) e pela Escala Modificada de Ashworth (EMA) antes e três semanas após o término do treinamento com a técnica. Os sujeitos foram submetidos ao biofeedback durante 6 semanas, com 2 sessões semanalmente. O mesmo tempo para o tratamento fisioterápico foi padronizado para o GC. Os resultados mostram variação do percentual médio de melhora do grau de espasticidade, mensuradas pelo LRET, de 38,59% (dp=13,03%) no GE comparado com 18,58% (dp=11,90%) do GC. Essa variação apresentou diferença significativa (p=0,020; t=2,776; p<5%) entre os grupos (controle e experimental), e a diferença significativa do LRET antes e após do treinamento no GE (p=0,003; t=5,338; p<5%) quando comparado ao GC (p=0,015; t=3,657; p<5%). A medida semi-quantitativa da EMA antes e após o término das sessões mostraram variações apenas no GE. Com relação a atividade cortical, houve diferença de atividade das bandas (delta, teta, alfa e beta) quando a 3ª e 12ª sessão foram comparadas para cada sujeito do GE. Essa diferença foi encontrada, principalmente, em regiões frontal, central (vértex), parietal e occipital em ambos hemisférios (ipsilateral e contralateral a lesão) tanto na fase de planejamento cognitivo motor quanto na execução do movimento. Houve predominância da diferença de atividade para a banda delta, alfa e beta em diferentes sujeitos distribuída difusamente ao longo dos canais de registro de viii EEG. A atividade diferenciada das bandas foi devido ao aumento e/ou diminuição da energia espectral entre as sessões, notado apenas em alguns voluntários do GE. Observou ainda diferença de atividade em áreas motoras secundárias. As avaliações, principalmente do LRET mostram que o treino com biofeedback EMG foi efetivo na redução do grau de espasticidade. A diferença de atividade cortical das bandas de frequência entre as sessões sugere que o biofeedback modula a cognição por meio do esforço e atenção imposta pela tarefa na tentativa do movimento no membro acometido. Além de que a diferença de energia espectral entre as sessões é dependente do ajuste e complexidade da tarefa direcionado pelos sinais do biofeedback, auxiliando na aprendizagem motora. / Spasticity is observed in most patients after cerebrovascular accident (CVA), and exerts influence in the presence of disabilities, affecting motor function. For neurorehabilitation strategies, electromyographic biofeedback (EMG) has been used with acceptance in the medical community for adjustments in the sensory-motor skills as a motor retraining, reducing spasticity and/or relaxation training. The intervention still presents limited evidence regarding their effectiveness in rehabilitation, especially as the interference of cortical activity and the reduction of spastic signs that provides negative characteristics in movement execution. The aim of this study was to analyze the workout possible interference with EMG biofeedback on the motor control awareness in spastic member in the characterization of the activity of low-frequency bands in different cortical regions targeted by the training technique. Sixteen volunteers affected by ischemic stroke were selected and divided into two groups (n = 8). Experimental group (EG) underwent biofeedback training associated with physical therapy and control group (CG) only conventional physiotherapy. The assessment of the degree of spasticity by reflex threshold of the tonic stretch (TSRT) and Modified Ashworth Scale (MAS) was performed before and three weeks after the end of treatment with the technique. The subjects underwent biofeedback for 6 weeks, with two sessions weekly. The same time for physiotherapy treatment was standardized to the GC. The results show variation of the average percent improvement in the degree of spasticity measured at TRST, 38,59% (sd=13,03%) in GE compared to 18,58% (sd=11,90%) of GC. This variation showed a significant difference (p=0.020; t=2,776; p<5%) between groups (control and experimental), and the significant difference of TRST before and after training in EG (p = 0.003; t=5,338; p <5%) when compared to the CG (p=0.015; t=0,015; p<5%). The semi-quantitative measure of the MAS before and after the end of the sessions presented variations only in GE. Regarding the cortical activity, there were band activities differences when 3rd and 12th sessions were compared for each subject of GE. This difference was found primarily in the frontal, central (vertex), parietal and occipital lobe in both hemispheres (contralateral and ipsilateral to the lesion) in both the cognitive motor planning phase and in the movement execution. It was observed the predominance of activity difference for the delta band, alpha and beta in different subjects distributed diffusely over the EEG recording channels. The different activity of the bands was due to the increase and/or decrease the spectral energy between sessions, x noticed only in some GE volunteers. It was also pointed out distinct activity in secondary motor areas. Evaluations mainly from TSRT show that training with EMG biofeedback was effective in reducing the degree of spasticity. The difference in cortical activity of the frequency bands between sessions suggested that biofeedback modulates cognition through the effort and attention required by the task of movement attempt in the affected limb. Besides that, the spectral energy difference between the sessions depends on the tuning and task complexity driven by biofeedback signals, helping motor learning. / Tese (Doutorado)

O objetivo deste estudo foi avaliar o efeito do biofeedback (BIO) associado à terapia ocupacional (TO) e à estimulação elétrica funcional (FES) na espasticidade, movimento ativo e função do membro superior de pacientes hemiplégicos. Este estudo foi realizado na Divisão de Medicina de Reabilitação do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Cinqüenta e nove pacientes acometidos por acidente vascular cerebral participaram do estudo por um ano; 31 receberam TO+FES duas vezes por semana + BIO uma vez por semana e 28 receberam somente TO+FES duas vezes por semana. Os pacientes foram avaliados inicialmente, após 6 meses e após 1 ano através da Avaliação da Função Manual, do Teste de Destreza Manual Minnesota, do Teste de Amplitude de Movimento e da Escala de Ashworth modificada. TO+FES+BIO melhoraram significativamente a amplitude de movimento e função dos membros superiores após 6 meses e 12 meses, quando comparado com somente TO+FES. Ambos os grupos melhoraram significativamente a espasticidade, após 6 meses e 12 meses, com diferença não significante entre eles. O uso adicional do biofeedback mostrou efeito positivo em amplitude de movimento e recuperação da função do membro superior no grupo estudado e pode representar uma importante ferramenta para a reabiltação de pacientes hemiplégicos / The objective of this was to study the effect of biofeedback (BIO) associated to occupational therapy (OT) and functional electrical stimulation (FES) on spasticity, range of motion and upper extremity function of hemiplegic patients. The study took part at the Division of Rehabilitation Medicine of the Hospital das Clínicas of the University of São Paulo School of Medicine. Fifty-nine stroke patients were studied for one year; 31 received OT+FES twice a week + BIO once-a-week and 28 received only OT+FES twice-aweek. The patients were evaluated initially, after six months and after one year with the use of Manual Function Evaluation, Minnesota Manual Dexterity Test, Range of Joint Motion Test and Modified Ashworth Scale. OT+FES+BIO significantly improved range of motion and upper extremity function after 6 months and 12 months, compared to only OT+FES. Both groups showed significant improvement of spasticity, after 6 months and 12 months, with no significant difference between them. The additional use of BIO had a positive effect in range of motion and function recovery of upper extremity in the studied group and may represent an important therapeutic tool for stroke rehabilitation

Foi comparada a massa óssea e a composição corporal dos hemicorpos dominante e não dominante de um grupo (A) de 16 pessoas com paralisia cerebral com hemiplegia espástica, e de um grupo (B) de 29 voluntários normais por meio da mensuração da massa corporal, estatura e densitometria óssea do corpo total com composição corporal. Foi encontrada diferença estatística significante no conteúdo mineral ósseo dos membros superiores do grupo A e dos membros superiores e inferiores, tronco e total do grupo B; na massa magra dos membros inferiores do grupo A e dos membros superiores e inferiores, tronco e total do grupo B; na massa adiposa dos membros inferiores do grupo A e dos membros superiores e inferiores, tronco e total do grupo B; e no conteúdo mineral ósseo dos membros superiores e inferiores, e total e na massa magra dos membros superiores e inferiores entre os hemicorpos não dominantes dos grupos A e B. Foi encontrada também correlação estatística significante entre o conteúdo mineral ósseo e a massa magra nos grupos A e B em todos os sítios, exceto no tronco dominante do grupo A; e o conteúdo mineral ósseo e a massa corpórea no tronco dominante do grupo A e no membro inferior dominante e bilateral do grupo B / Were compared the bone mass and body composition of the dominant and nondominant hemi bodies in a group (A) of a 16 spastic hemiplegic cerebral palsy and in a group (B) of 27 normal volunteers by weight, height, and densitometry of total body with body composition measure. Were observed significant statistical difference in the bone content mineral of the upper limbs of the group A and of the upper and lower limbs, trunk and total of the group B; in the lean mass of the lower limbs of the group A and of the upper and lower limbs, trunk and total of the group B; in the mass fat of the lower limbs of the group A and of the upper and lower limbs, trunk and total of the group B; and in the bone mineral content of the upper and lower limbs, and total, and in the lean mass of the upper and lower limbs between the hemi bodies no dominant of the A and B groups. Were observed too statistical correlation between the bone mineral content and lean mass in the groups A and B in all locals, except in the trunk of group A; and between the bone mineral content and body mass in the trunk of group A and lower limb dominant and bilateral of group B

La spasticité est l’une des nombreuses complications motrices qui peuvent apparaître après une lésion de la moelle épinière. Elle est présente dans 75 % des patients médullo-lésés et se caractérise par une hypertonie musculaire en réponse à un réflexe d’étirement. Les traitements actuels, qui ciblent les symptômes et non les causes de la spasticité, sont peu efficaces. Bien que les mécanismes neurologiques qui sous-tendent la spasticité soient complexes et restent en grande partie méconnus, un certain consensus se dégage sur le fait qu’elle est associée à une hyperexcitabilité intrinsèque des motoneurones et à une levée de l’inhibition des réflexes spinaux. L’hyperexcitabilité motoneuronale se manifeste par une décharge soutenue de potentiels de plateau et résulte en partie d’une augmentation des courants entrants persistants sodiques (INaP). La désinhibition découle, en partie, d’une baisse de l’expression des cotransporteurs potassium-chlorure de type 2 (KCC2) à la membrane des motoneurones, modifiant ainsi le gradient électrochimique des ions Cl- et donnant un caractère excitateur aux deux principaux neurotransmetteurs inhibiteurs que sont le GABA et la glycine. Néanmoins, les mécanismes à l’origine des dérégulations du courant INaP et des co-transporteurs KCC2 ne sont toujours pas élucidés. / Spasticity is commonly caused by several pathologies and specifically after a spinal cord injury (SCI). Spasticity is usually associated with hypertonia, clonus, muscle spasm and pain. The present thesis aims to identify the upstream mechanism in the pathophysiology of spasticity Calpain, a calcium-activated cysteine protease, has been shown to participate in the development of the inflammatory processes after SCI. Of special interest, some determinants governing the inactivation of sodium (Na+) channels are sensitive to proteases and their proteolytic cleavage prevents inactivation of Na+ channels. As a result, INaP is strongly increased. It is worth mentioning that the C-terminal domain of KCC2 is also sensitive to proteases which alter KCC2 ability to extrude Cl- ions. Among the different proteases, calpains are able to truncate both Na+ channels and KCC2 transporters. This led us to consider the exciting possibility that a proteolytic cleavage of both Na+ channels and KCC2 by calpains could compose an upstream inflammatory mechanism contributing to the development of spasticity after SCI. My thesis demonstrates that the cleavage of Na+ channels and KCC2 by calpain after SCI, is responsible for the upregulation of INaP and disinhibition of motoneurons, that both act synergistically to generate spasticity. Calpain inhibition by MDL28170 reduced the cleavage of both Na+channels and KCC2 associated with a respective downregulation of INaP, hyperpolarizing shift of the EIPSP, and an alleviation of spasticity. The thesis represents a significant breakthrough by opening novel perspectives to develop therapies.

Title: The effect of progressive static stretching on treatment of spastic paraparesis in patients with cerebral palsy Objectives: The goal of this dissertation is to evaluate the effect of progressive static stretching on treatment of spastic paraparesis in patients with paraparetic form of cerebral palsy (CP). Elements chosen for the treatment were those of the therapeutic concept Guided Self-rehabilitation Contract by French professor Jean-Michel Gracies, which is presented in detail in the theoretical part of the dissertation. Methodology: This dissertation has a theoretical-empirical character. First theoretical part of the dissertation is in a form of a research on the topic of spasticity and diagnosis and treatment of spastic paresis according to the concept of J.-M. Gracies. Second experimental part of the dissertation evaluating the effect of the selected treatment for spastic paresis in people with cerebral palsy, has a form of pilot qualitative research, which was attended by 6 participants. At the beginning of the research each participant has undergone an entrance examination that evaluated spasticity using at first an unique assessing protocol Five step clinical assessment and consequently a surface electromyography. Based on this examination, each participant was instructed to follow...