Prolonged perinatal ischaemia is an important factor in the development of periventricular leukomalacia (PVL), which is the most common white matter pathology associated with cerebral palsy (CP): approximately 1.5 to 2.5 per 1,000 live births per year suffer from CP. During central nervous system (CNS) ischaemia, there is an excessive accumulation of extracellular neurotransmitters. Ischaemia affects axons and glial cells of white matter, which occupy approximately 50% of the human brain. The mechanisms of ischaemic-induced injury in astrocytes vary at different ages. Ischaemic injury in postnatal day 0 (P0) of rat optic nerve (RON) astrocytes is Ca[superscript 2+]-dependent and mediated by voltage-gated Ca[superscript 2+] channels (VGCCs). Astrocytes are replete with neurotransmitter receptors. Using an ex vivo model of ischaemia (oxygen-glucose deprivation: OGD) and Ca[superscript 2+] imaging, I investigated the role of gamma-aminobutyric acid (GABA), glycine, nicotine and norepinephrine in P0 RON during ischaemia. OGD produced a rapid and significant increase in cell death. A GABA antagonist (picrotoxin), a glycine antagonist (strychnine) and their combination protected P0 RON astrocytes from ischaemic injury. They reduced the total percentage of cell death and postponed the initial cell death. Immunohistochemistry revealed that GABA and glycine receptors are expressed by astrocytes and axons in P0 RON. On the other hand, blocking nicotinic acetylcholine receptors (nAChRs: mecamylamine or α-bungarotoxin) or blocking adrenergic receptors (combination of propranolol and phentolamine) had no effect. Using a glial injury scoring system, ultrastructural studies confirmed the protective action of picrotoxin and strychnine against ischaemia, which cannot be achieved by mecamylamine or a combination of propranolol and phentolamine. Chondroitin sulphate proteoglycans (NG2) (+) cells are a distinct type of glial cell which, over time, have come to be known as the fourth type of glia. These cells are distributed throughout the developing and adult CNS, and are known to be mitotically active even in the adult CNS. The astrocyte fate of NG2 (+) cells is a matter of debate. In the current study, the focus was on studying the morphological features of NG2 (+) cells at the ultrastructural level and under confocal microscope, and more precisely their relation to astrocytes in nRON following post-embedding immunolabelling. Immuno-electron microscope (I-EM) revealed NG2 immunoreactivity in nRON astrocytes. Double immunolabelling showed an overlap between NG2 (+) and (glial fibrillary acidic protein) GFAP (+) populations in nRON, adult RON and cortical grey matter.

Introduction: Research suggests that children with disabilities are at increased risk of experiencing psychological difficulties. Cerebral palsy is the most common cause of physical disability in childhood and one that has been investigated mostly from the stance of the parent. Given this, the current study aimed to investigate the experience of living with cerebral palsy from the perspective of the child. Design: Eight children (aged 9-12 years) diagnosed with cerebral palsy and attending mainstream schools were recruited. A qualitative cross-sectional design was adopted and data were collected via a series of semi-structured interviews. Transcripts were coded using Interpretative Phenomenological Analysis. Results: Four super-ordinate themes were identified: sense of self, participation, autonomy versus dependency, and dealing with others. Themes are discussed in relation to relevant literature. Discussion: Issues raised by participants suggest that children with cerebral palsy encounter both attitudinal and structural barriers to achieving similar developmental tasks as their peers. The impact of which may result in feelings of being different from peers, of rejection and hopelessness, all of which may impact on their sense of self and lead to psychological difficulties. Children with cerebral palsy should be supported in achieving independence and professionals should be aware that males and females may differ in both the issues they face and the methods through which they cope. Screening for the early identification of psychological difficulties is strongly recommended. Parents and professionals also need to be informed of the impact that the school environment may have on children with cerebral palsy.

Complex orthopaedic surgery is often indicated in the management of deformity in children with spastic diplegic cerebral palsy (CP) and a long rehabilitation programme is important for a successful outcome. However, the frequency and content of physiotherapy treatment following surgery varies between centres. This thesis aimed at providing a scientific basis for post-operative rehabilitation following multi-level surgery in children with CP. The effect of muscle weakness on function in patients with CP is recognised. However, the short and long-term impact of multi-level orthopaedic surgery on muscle strength is unclear. Strength changes would have implications for both surgical and conservative treatment planning. The objectives of this study were to establish a better understanding of the impact of surgery on muscle strength, gait and function, as well as the natural history of weakness in CP. Furthermore, the study aimed to clarify whether physiotherapy, focused on resistance strengthening techniques, was more effective than routine physiotherapy. The reliability of a protocol for measuring muscle strength in lower limb muscle groups in this population was firstly established. A pilot study of 10 children with a diagnosis of spastic diplegic CP and healthy counterparts demonstrated a reliable strength testing protocol. The main study of 20 diplegic children who underwent multi-level surgery showed that despite improvements in gait parameters, significant loss of strength in lower limb muscle groups and gross motor function persisted at six months. The value of intensive physiotherapy was assessed in a randomised controlled trial six months after surgery. Advantages of resistance training over active exercise were demonstrated. Assessment at one year showed that surgical patients preserved the post-physiotherapy strength and function gains but these did not reach the pre-operative values. Another group of 10 diplegic children who received routine physiotherapy but no surgical treatment for 12 months showed significant deterioration of their gait. The rate of deterioration demonstrated in conservatively treated diplegic patients and the degree of weakness caused by surgery, should inform parents and clinicians during decisions regarding surgery. Future research in multi-level surgery should include specific strength assessment protocols. The results from the randomised clinical trial showed that overall intensive strengthening regimes after multi-level surgery are beneficial. This finding would have significant implications on managing resources and designing appropriate rehabilitation programmes after multi-level orthopaedic surgery.

La paralysie cérébrale est la pathologie motrice la plus commune dans l’enfance, elle engendre tous types de troubles principalement moteurs. La parole peut notamment être touchée affectant parfois profondément les capacités communicatives des enfants. Les thérapies pour pallier les troubles moteurs de la parole manquent d’efficacité. C’est dans ce cadre que le logiciel RePliCa a été développé afin de rendre leur rééducation plus efficiente. Une variable, encore peu documentée dans le cadre de la rééducation, est identifiée comme influençant grandement les progrès, il s’agitde l’engagement. L’engagement est considéré comme malléable et sensible aux changements environnementaux et pourrait donc être influencé par l’introduction d’un logiciel dans la rééducation. La première partie de cette thèse était consacrée à l’optimisation de cet outil. Dans cet objectif, une série d’études expérimentales a été menée auprès d’enfants au développement typique et a permis l’intégration d’un certain nombre de caractéristiques relatives à l’interface influençant positivement l’engagement. Une grille d’observation a ensuite été créée afin d’évaluer l’engagement des enfants paralysés cérébraux dans la rééducation lors du programme pilote avec le logiciel. L’étude clinique montre des résultats encourageants, l’engagement semblant se maintenir au cours des séances. Ces résultats sont mis en perspectives dans le cadre d’un modèle de l’engagement. / Cerebral Palsy is the most common physical disability in early childhood, resulting in multiple disorders, primarily of motor skills. Speech especially can be impacted and deeply affects children’s communicative abilities. The RePliCa software wasdeveloped to improve the efficiency of motor speech therapy. One variable, engagement, has not been fully researched in the field of rehabilitation but has been identified influential for children’s progress. Engagement is presumed to bemalleable and sensitive to environmental changes and therefore could be influenced by the introduction of software in rehabilitation. The first part of this thesis was devoted to its optimization. To this end, a series of experimental studies wereconducted, enabling the integration of a number of features on the interface in order to promote engagement. Once the software was implemented, engagement in rehabilitation was examined in a clinical study. Results showed encouraging results: engagement can be maintained over time. Results are put in perspective using an engagement model framework

L’Afrique est confrontée à un vieillissement démographique sans précédent. L’âge étant le facteur principal dans la survenue des démences, l’Afrique devra affronter l’un des plus grands risques socio-sanitaire et économique du 21e siècle. Cette situation accentue la pression sur des systèmes nationaux de santé sollicités au-delà de leurs capacités. L’épidémiologie des démences est encore très peu connue en Afrique et la plupart des données existantes portent sur la prévalence. La démence étant une pathologie chronique et actuellement incurable, la prévention et l’amélioration de la qualité de la prise en charge des malades restent les meilleures armes pour la gestion de cette pathologie. Pour mieux aider les pays africains à bâtir des politiques de santé adaptées, il est important de fournir des données portant sur l’évolution (incidence et mortalité) de cette pathologie. L’objectif de nos travaux était d’estimer l’incidence des démences et le pronostic de ces pathologies en terme de survie. Notre travail a été réalisé à partir d’une cohorte de sujets âgés, habitant les zones urbaine et rurale de la République du Congo, recrutés lors de l’enquête de prévalence EPIDEMCA et suivis pendant deux ans entre 2012 et 2014. Dans un premier temps nous avons estimé la mortalité associée à la démence. La comparaison des taux de mortalité en fonction du statut cognitif a montré que les sujets déments avaient un risque de décès plus important. Ce risque était 2,5 fois plus élevé par rapport aux sujets normaux (HR= 2,53, IC95%: 1,42-4,49, p=0,001) et augmentait avec l’âge et la sévérité de la maladie. Concernant l’incidence, nous avons observé 23 (2,38%) nouveaux cas de démence et estimé une incidence brute de 15,79 (IC95% :10,25 – 23,32) pour 1000 Personne Année (PA). L’incidence standardisée à la population âgée d’Afrique Subsaharienne S était de 13,53 (IC95% 9,98 – 15,66). En tenant compte des différents facteurs analysés, l’âge (p=0,003) et un faible engagement social (p=0,028) (défini par un manque ou une faible participation aux activités communautaires) étaient les principaux facteurs associés à l’incidence de la démence en population congolaise. Globalement, nos résultats soulignent le fardeau que représente la démence pour l’Afrique et sont en parfaite adéquation avec ceux issus d’autres pays à faibles et moyens revenus et des pays à revenus élevés. Toutefois, il est difficile de généraliser nos résultats à la population africaine, car il s’agit d’un continent vaste avec des spécificités pour chaque population. La mise en place de programmes d’études multicentriques dédiés aux démences adoptant des méthodologies similaires serait souhaitable. Les politiques de santé relatives aux personnes âgées devraient intégrer la prise en charge des démences. / The African population is ageing at an unprecedented rate. In sub-Saharan Africa (SSA), the number of people aged 60 years and above is projected to rise to over 67 million by 2030 (representing a 100% increase in the 25 years since 2005). Incidence and mortality data help us understand the epidemiology and disease burden of dementia, and thereby improve policy planning. Although dementia prevalence have been reported for many countries of SSA, incidence and mortality related to dementia remain poorly described to date as only Nigeria had reported dementia incidence among older African adults. This study aimed to assess the dementia related incidence and mortality, and associated risk factors in Congolese people aged over 65 years recruited in EPIDEMCA survey. The baseline population was followed up during two years. Older participants were traced and interviewed annually in rural and urban Congo between 2012 and 2014. DSM-IV and NINCDS-ADRDA criteria were required for dementia and Alzheimer’s disease diagnoses. Data on vital status were collected throughout the follow-up. Cox proportional hazards model was used to assess the link between baseline dementia diagnosis and mortality risk. Risk factors for incident dementia were examined using a competing-risks regression model based on Fine and Gray methods. After two years of follow-up, 101 (9.8%) participants had died. Compared to participants with normal cognition at baseline, mortality risk was more than 2.5 times higher among those with dementia (HR= 2.53, 95% CI: 1.42-4.49, p=0.001). Among those with dementia, only clinical severity of dementia was associated with an additional increased mortality risk (HR=1.91; CI 95%, 1.23-2.96; p=0.004). Age (per 5-year increase), male sex and living in an urban area were independently associated with increased mortality risk across the full cohort. Among the dementia-free cohort, the crude incidence of dementia was estimated at 15.79 (95% CI 10.25 – 23.32) per 1000 Person Year. We estimated a standardised incidence (on the 2015 Sub-Saharan Africa population) of 13.53 (95% CI 9.98–15.66). Regarding baseline characteristics, old age (p=0.003) and poor social engagement (assessed by community activity) (p=0•028) at baseline were associated with increased dementia incidence among Congolese older adults.Our results, as previously described, support the ongoing demographic and epidemiologic transition in SSA. They highlight the need of longitudinal population-based studies dedicated to dementia incidence and mortality among African people. Given that Africa is a continent subject to unprecedented population ageing; our data highlight the need to address the burden of dementia in this region. Support should incorporate prevention plans based primarily on modifiable (cardiovascular) risk factors, education and social inclusion of the elderly, as well as support for patients and their relatives.