Cerebrospinal fluid (CSF) infusion tests can be used to estimate the dynamic properties of the CSF system. Idiopathic normal pressure hydrocephalus (INPH) is a syndrome signified by a disturbance to the CSF system, where the cause is unknown and the diagnosis is difficult to determine. As an aid in identifying patients with INPH who will improve after shunt surgery, infusion tests are commonly used to determine the outflow conductance (Cout), or outflow resistance (Rout=1/Cout), of the CSF system. The tests are also used to determine shunt function in vivo. The general aim of this thesis was to develop and validate CSF infusion methods, to investigate the dynamics of the CSF system. The methods should be applicable to patients with INPH, to aid in the quest to further improve the diagnosis and management of this syndrome. An existing mathematical model describing the dynamics of the CSF system was further developed. The characteristics of the model were verified and the effect of expanding intracranial air on the intracranial pressure (ICP) was simulated. The simulations supported the recommendation to maintain sea-level pressure during air ambulance transportation of patients with suspected intracranial air. A recently developed infusion apparatus was evaluated, on an experimental model as well as on a patient material. The repetitiveness in estimating Cout was found to be good. A statistically significant difference was found between the repeated Cout estimations in the patient group, indicating that there might have been a small physiological change introduced during the infusion test. A parameter, ∆Cout, was proposed and evaluated. It proved to reflect the reliability of individual Cout investigations in a clinically useful way, as well as to provide easily interpreted information. An adaptive algorithm for assessment of Cout was developed and evaluated on a patient group. The new algorithm was shown to reduce the investigation time, from 60 minutes, by 14.3 ± 5.9 minutes (mean ± SD), p<0.01, without reducing the reliability of the estimated Cout below clinically relevant levels. The relationship between ICP and CSF outflow was studied in a group of patients investigated for INPH. It was found that in the range of moderate increase from baseline pressure, the assumption of a pressure independent Rout was confirmed (p=0.5). However, at larger pressure increments, the relationship had a non-linear tendency (p<0.05). This indicates that the traditional view of a pressure independent Rout might have to be questioned in the region where ICP exceeds baseline pressure too much. Infusion tests can be performed in different ways, where three main categories may be distinguished. The bolus infusion method was compared to the constant pressure and constant flow infusion methods, on an experimental model as well as on a patient material. When physiological pressure fluctuations were added to the model, significant differences were found in the determination of Cout in the range of clinical importance, i.e. low Cout (p<0.05). The finding was supported by the patient investigations, the difference was however not significant. With the application of the new methods developed in this thesis, and the increased knowledge concerning relationships between CSF dynamic parameters, the CSF infusion test was further improved with the ability to increase measurement reliability in a reduced time. This constitutes a good basis to perform a large multi-centre study with the main goal to determine the predictive value of the parameter Cout.

Normal pressure hydrocephalus (NPH), a CSF circulation disorder, is important as a reversible cause of gait and cognitive disturbance in an aging population. The inconsistent response to CSF shunting is usually attributed to difficulties in differential diagnosis or co-morbidity. Improving outcome depends on an increased understanding of the pathophysiology of NPH. Specifically, this thesis examines the contribution of, and inter-relationship between, the brain parenchyma and CSF circulation in the pathophysiology of NPH. Of the four core studies of the thesis, the first quantifies the characteristics of the CSF circulation and parenchyma in NPH using CSF infusion studies to measure the resistance to CSF absorption and brain compliance. The second study assesses cerebral blood flow (CBF) was using O15-labelled positron emission tomography (PET) with MR co-registration. By performing CSF infusion studies in the PET scanner, CBF at baseline CSF pressure and at a higher equilibrium pressure is measured. Regional changes and autoregulatory capacity are assessed. The final study examines the microstructural integrity of the parenchyma using MR diffusion tensor imaging. These studies confirm the importance of the inter-relationship of the brain parenchyma and CSF circulation. NPH symptomatology and its relationship to the observed regional CBF reductions in the basal ganglia and thalamus are discussed. Regional CBF reductions with increased CSF pressure and the implications for autoregulatory capacity in NPH are considered. The reduction in CBF when CSF was increased was most striking in the periventricular regions. In addition, periventricular structures demonstrated increased diffusivity and decreased anisotropy. The relationship between these changes and mechanisms such as transependymal CSF passage are reviewed. The findings of this thesis support a role of both the CSF circulation and the brain parenchyma in the pathophysiology of NPH. The results have implications for the approach to the management of patients with NPH.

The global population is predicted to increase to around 11 billion by 2100. By 2050, the average age in the most populous age group will be over sixty. The ageing population (over sixty-five) is projected to exceed the number of children by 2047. These demographics imply that as the ageing population section increases, there will be a greater need for long-term care services. In order to adequately prepare against this trend, medical experts and evidence-driven policymakers are realising that personalised healthcare can help alleviate the burden related to the planning and commissioning of services allied to long-term care. Central to this picture is conditions that affect the brain - the most important organ of the human body. Dementia, stroke, and other conditions have a tremendous impact on loss of life, quality of life and healthcare cost. The challenge regarding brain disease is exacerbated further due to the difficulty regarding accessibility of this organ, but also due to the immense complexity regarding its morphology and functionality. In this context, advanced biophysical modelling is considered a promising option for studying brain pathophysiology and becomes a priority investment regarding routes for brain research. Simulations offer the promise of improved, clinically relevant, predictive information, acceleration for the pipeline of drug discovery/design and better planning of long-term care for patients. Within this paradigm, a particular model of water transport in the cerebral environment is essential. Numerous brain disorders arise from water imbalance in the cerebral environment, such as hydrocephalus (HCP), oedema and Chiari malformations to name a few. In this research, a novel multiscale model of fluid regulation and tissue displacement in the cerebral environment is developed, arising from the use of Multiple-network Poroelastic Theory (MPET). Characteristics of a four-network poroelastic model (4MPET) are first explored. Then, this model is extended to a fully dynamic (transient) six-network model (6MPET) via the addition of two new compartments, namely the glial cells compartment and the glymphatic system compartment. The introduction of these two compartments in the MPET paradigm reflects recent seminal findings in cerebral physiology, namely the extent and importance regarding transport/clearance of the perivascular spaces of the brain vasculature. We develop and present a numerical implementation of the 6MPET model, and we utilise this framework to analyse acute HCP and cerebral oedema in a variety of settings, in order to show the enhanced capability of the proposed 6MPET model compared to the classical 4MPET. Investigations of acute hydrocephalus through the fully dynamic 6MPET reveal compensatory trans-ependymal pressure behaviour in the glymphatic compartment. It was also shown that aquaporin-4 (AQP4) deficient expression exaggerates ventriculomegaly, and this too is demonstrated in acute hydrocephalus. Additionally, using the 6MPET model, one is able to witness three mitigating factors for cytotoxic oedema. Specifically, these are: reducing water mobility in the glial cells compartment, increasing the compliance of the glial cells compartment and finally AQP4-deficient expression.

A hidrocefalia é uma síndrome complexa caracterizada pelo acúmulo de líquido cérebro-espinal no interior das cavidades ventriculares. Considerando a sua fisiopatologia de caráter multifatorial sendo um dos fatores envolvidos o estresse oxidativo desencadeado pela peroxidação lipídica e formação de radicais livres, este trabalho visa estudar o possível efeito neuroprotetor proveniente do polifenol galato de epigalocatequina (EGCG) na hidrocefalia experimental. Foram utilizados ratos da linhagem Wistar (N=56), com 7 dias de idade. Os filhotes foram submetidos à indução da hidrocefalia pelo método da injeção intracisternal de caulim a 20%. O polifenol foi administrado intraperitonealmente por 9 ou 20 dias consecutivos a partir da indução da hidrocefalia. Aferição do peso corporal diário e testes comportamentais foram realizados. Dez ou 21 dias após a indução da hidrocefalia os animais, profundamente anestesiados, foram sacrificados através da perfusão cardíaca com solução salina. Seus encéfalos foram removidos, fixados com paraformaldeído 3% em tampão fosfato 0,1M e processados para inclusão em parafina. Preparações histológicas foram realizadas para a análise por coloração hematoxilina eosina, solocromo-cianina e imunoistoquímica para GFAP e Ki67. Os diferentes parâmetros de avaliação demonstraram que os animais tratados com o polifenol por 9 dias consecutivos apresentaram redução da atividade astrocitária através da imunomarcação pelo GFAP no corpo caloso, cápsula externa e matriz germinativa; além de apresentarem corpo caloso mais espesso e mielinizado, exibindo uma tonalidade azul mais intensa evidenciada pela coloração solocromocianina. Apesar desses resultados demonstrarem um possível efeito neuroprotetor na fase inicial de instalação da doença, estudos adicionais devem ser realizados para obtenção de uma terapêutica eficiente e segura para o aprofundamento com testes clínicos. / Hydrocephalus is a complex syndrome, characterized by the accumulation of cerebrospinal fluid in cerebral ventricles. Considering its multifactorial pathophysiology, one of the factors being the oxidative stress triggered by lipid peroxidation and free radical formation, this work aims to study the possible neuroprotective effect of the polyphenol epigallocatechin gallate (EGCG) in experimental hydrocephalus. Seven-day old Wistar rats (N=56) were used in this study. The pups were subjected to hydrocephalus induction by kaolin 20% through intracisternal injection. The polyphenol was administered intraperitoneally for 9 or 20 days from the induction of hydrocephalus. Measurement of daily body weight and behavioral tests were performed. The animals, deeply anesthetized, were sacrificed by cardiac perfusion with saline 10 or 21 days after induction of hydrocephalus. Their brains were removed, fixed with 3% paraformaldehyde in 0.1 M phosphate buffer, and processed for paraffin embedding. Preparations were made for histological analysis by hematoxylin and eosin, solochrome-cyanine and immunohistochemistry for GFAP and Ki67. The different evaluated parameters showed that animals treated with the polyphenol for 9 consecutive days displayed reduction on the reactive astrocytes GFAP immunostaining at the corpus callosum, external capsule and germinal matrix, also having thicker and more myelinated corpus callosum exhibiting a more intense blue staining by solocromo-cyanine. Although these results demonstrate a possible neuroprotective effect at the initial onset of the disease, additional studies should be performed to obtain an effective and safe therapy for deeper studies in clinical trials.

Introdução. A hidrocefalia é uma doença de complexa fisiopatologia, que não só afeta a dinâmica do líquido cefalorraquidiano (LCR), mas também outras estruturas do sistema nervoso central, e consequentemente pode trazer sequelas graves em crianças. Sua fisiopatologia, principalmente no nível bioquímico-celular, ainda é pouco conhecida. Objetivos. Avaliar aspectos clínicos (ganho ponderal, comportamento motor e memória), radiológicos (razão ventricular e transferência de magnetização), histopatológicos (astrocitose reativa e proliferação celular na matriz germinativa) e bioquímicos (presença de interleucinas inflamatórias no líquor) na fase aguda da hidrocefalia experimental induzida por caulim e o efeito do tratamento com derivação adaptada (ventrículo-subcutânea). Materiais e métodos. Utilizaram-se ratos Wistar com 7 dias de vida, que foram divididos em três grupos: controle sem injeção de caulim (n = 5), hidrocefálico sem tratamento (n=17), e hidrocefálico tratado com derivação ventrículo-subcutâneo (DVSC), a partir do 7o dia pós-indução (n=24). Os animais dos grupos hidrocefálicos tratado e não tratado receberam uma injeção de caulim a 15% na cisterna magna, para a indução da hidrocefalia, no 7o dia do estudo. Resultados. O ganho de peso foi semelhante nos grupos hidrocefálicos mas menor que no grupo controle. Animais tratados e não tratados exibiram desempenho inferior aos controles no comportamento motor pelo teste Open Field, ao passo que o desempenho no teste de memória foi melhor no grupo tratado. A DVSC reduz drasticamente as dimensões ventriculares, porém não reverte a desmielinização causada pela hidrocefalia, como visto na avaliação por ressonância magnética. Da mesma forma, os processos de astrocitose reativa (que aumenta com a hidrocefalia) e proliferação na matriz germinativa (que se reduz) não se alteram após o tratamento com a DVSC. A hidrocefalia aumenta os níveis liquóricos das interleucinas 1? e 6 e TNF-?, que retornam ao normal após o tratamento. Conclusões. O tratamento com a DVSC foi eficaz (considerando-se a redução ventricular) e trouxe benefícios comportamentais e celulares, porém não foi suficiente para alterar o curso dos processos de injúria e reparação celular cerebral já estabelecidos. Depreende-se que há participação de mecanismos inflamatórios neste modelo de hidrocefalia experimental a partir do achado de aumento de interleucinas inflamatórias no líquor / Introduction. Hydrocephalus is a complex disease, which affects not only cerebrospinal fluid dynamics, but also other cerebral structures, and therefore may result in severe disability for children. Its pathophysiology is still widely unknown, especially on a cellular-biochemical level. Objectives. Assessment of clinical (weight gain, behavior), radiological (ventricular index and magnetization transfer ratio), histopathological (reactive astrocytosis and cell proliferation over the germinal matrix) and biochemical (dosage of inflammatory interleukins) aspects of acute kaolin-induced experimental hydrocephalus and the effects of the treatment with an adapted shunt (ventricular-subcutaneous). Methods. 7-day-old Wistar rats were divided into three groups: untreated hydrocephalic (n=17), hydrocephalic treated with shunt on the 7th day after induction (n=24) and controls (n=5). Hydrocephalic animals, both treated and untreated, were injected with a 15% kaolin solution on the cisterna magna, to produce hydrocephalus. Results. Weight gain was similar on both hydrocephalic groups but lower than in controls. Motor behavior was also worse than controls for both groups, but treated animals showed better memory performance than their untreated counterparts. Shunting drastically reduces ventricular size, even though it does not reverse demyelination caused by hydrocephalus, as seen in magnetic resonance scanning analyses. Likewise, reactive astrocytosis and cell proliferation at the germinal matrix do not change after treatment. Interleukins 1? and 6 and TNF-? levels are raised in hydrocephalic rats and return to normal after shunting. Conclusions. The ventricular-subcutaneous shunt for treatment of kaolininduced hydrocephalus in rats is effective (i.e, reduces ventricular size) and has clinical and histological benefits, but is not enough to change the evolution of previously established injury and cellular reparation processes on the hydrocephalic brain. The finding of raised inflammatory interleukins on the cerebrospinal fluid suggests a role for inflammation in the pathogenesis of this experimental model of hydrocephalus

Hydrocephalus is a disease frequently mentioned in literature, but, the caregivers‟ knowledge about the disease is not well assessed. To characterize the caregivers of hydrocephalus patients; identify the fonts of formation to assume activities how to care; to verify caregivers‟ knowledge about hydrocephalus; to relate the caregiver‟ knowledge and level of child complications. Descriptive, exploratory and quantitative study, using a standardized interview technique. The survey was performed with caregivers at Aracaju University Hospital between November 2007 and August 2008. Fifty-four caregivers answered the interview. The mean age was 27.3 ± 7 years, with absolute predominance of females. There was a positive correlation on the number that they had left to work to be caregivers. Twenty-five caregivers (46.3%) received information about how to care and 53.7% learned to take care by themselves. The education level of the caregiver had a significant effect on the knowledge about definition, causes, complications, surgery and the shunt objectives. The knowledge about complications and surgery was significantly bigger in caregivers of children with sequels (P=0.003). The caregivers received little professional information. The education level of the caregiver had a positive correlation to on increased knowledge. Caregivers of children with sequels were related to on increased knowledge about important aspects on hydrocephalus. / A hidrocefalia é uma situação muito relatada na literatura, no entanto, pouco se tem discutido sobre os saberes dos cuidadores de crianças com hidrocefalia. Caracterizar cuidadores de crianças com hidrocefalia; identificar as fontes de formação de preparo para assumir os cuidados; verificar o conhecimento dos cuidadores sobre aspectos importantes da hidrocefalia; verificar a relação entre o conhecimento do cuidador e a presença de sequelas na criança. Estudo descritivo, exploratório, sob abordagem quantitativa, utilizando a técnica da entrevista padronizada, com cuidadores atendidos no ambulatório de um hospital universitário da cidade de Aracaju no período de novembro de 2007 a agosto de 2008. A amostra foi composta por 54 crianças e seus cuidadores. A média da idade do cuidador foi 27,3 ± 7 anos, com predomínio absoluto do gênero feminino. Observou-se um efeito significativo sobre o número das que deixaram de trabalhar para ser cuidadora. Vinte e cinco cuidadoras (46,3%) receberam orientações e 53,7% aprenderam a cuidar sozinhas. Houve relação significativa entre a escolaridade do cuidador e maior conhecimento de definição e causas da hidrocefalia, complicações, objetivo da cirurgia e finalidade da derivação ventricular. O conhecimento sobre o objetivo da cirurgia e complicações cirúrgicas foi significativamente maior em cuidadores de crianças com seqüelas (P=0,003). As cuidadoras receberam pouca orientação profissional. A escolaridade do cuidador foi significativa para maior conhecimento. Cuidadoras de crianças com seqüelas apresentam maior conhecimento sobre aspectos importantes da hidrocefalia.

Motor Function Evaluation of Hydrocephalus Children Background: Hydrocephalus constitutes a pathological condition that is manifested through signals and symptoms, including neurological and motor deficits that can result functional ability limitations. However, there are few studies that show the motor function of children with this illness. Objectives: To evaluate the kinetic and functional framework of hydrocephalus children; to identify the condition of muscle tone; to check the static and dynamic functional activities; to verify the association between tone alterations and functional activities in hydrocephalus children. Methods: A cross-sectional, descriptive, exploratory and field study, using qualitative and quantitative approach, performed at the University Hospital in Aracaju city, from August 2009 to March 2010. Results: From 50 evaluated children, 30 (60%) had hypertonia; 10 (20%) were hypotonic; and 10 (20%) showed no muscle tone alteration. The age average was considerably lower in hypertonic children and higher in hypotonic and without tone alteration children. The average of carried through surgeries was more expressive in hypertonic children. Motor sequels were present in 92% of the sample. The static functional activities, as well as dynamic ones, were lower in hypertonic children and higher in hypotonic and normal tone children. Conclusions: Muscle tone exacerbation is more present in hydrocephalus children and motor function is impaired, being the neuropsychomotor development delayed more evident in spastic children group and less pronounced in children with normal muscle tone. / Fundamento: A hidrocefalia constitui uma condição patológica que se manifesta através de sinais e sintomas, incluindo déficits neuromotores que podem resultar em limitações nas habilidades funcionais. No entanto, há poucos estudos que avaliem a função motora de crianças com esta doença. Objetivos: Avaliar o quadro cinético-funcional de crianças com hidrocefalia; identificar a condição do tônus muscular; verificar as atividades funcionais estáticas e dinâmicas; verificar a associação entre as alterações de tônus e as atividades funcionais nas crianças com hidrocefalia. Métodos: Estudo transversal, de caráter descritivo, exploratório e de campo, sob abordagem quali-quantitativa, realizado no ambulatório do Hospital Universitário, do município de Aracaju, no período de agosto de 2009 a março de 2010. Resultados: Das 50 crianças avaliadas, 30 (60%) apresentavam hipertonia; 10 (20%) eram hipotônicas; e 10 (20%) não apresentavam alteração de tônus muscular. A média de idade foi consideravelmente menor nas crianças hipertônicas em relação às crianças hipotônicas e normotônicas. O número de procedimentos cirúrgicos realizados foi mais expressivo no grupo de crianças com hipertonia muscular. As sequelas motoras estiveram presentes em 92% da amostra. As atividades funcionais estáticas, bem como as dinâmicas, encontraram-se mais comprometidas nas crianças hipertônicas do que nas hipotônicas e normotônicas. Conclusões: A hipertonia muscular foi a alteração tônica mais presente nas crianças com hidrocefalia, e a função motora é deficitária, sendo o atraso no desenvolvimento neuropsicomotor mais evidente no grupo de crianças espásticas e menos pronunciado nas crianças com tônus muscular sem alterações.

Hydrocephalus is a complex disease that can present many clinical manifestations compromising the growth and development of the child. Complication risks as infectious processes and impairment of the immune system can be attenuated in presence of nutritional deficiencies. However, studies about nutritional state and nutritional deficiencies of children with hydrocephalus are rare. Objective: To describe the nutritional profile of children with hydrocephalus. Methods: This is a cross-sectional, was developed at Neurosurgery Ambulatory of the University Hospital in Sergipe from August 2010 to May 2011. The data collected refer to social-economic, health, anthropometry, lab exams and food consumption conditions. Results: the results showed that from the 35 children studied, 17,1% were low weight, 31,4% malnourished with impairment of linear growth, 40,0% anemia, 37,2% presented low levels of pre-albumin. The consumption of energy, lipids, calcium, folic acid, vitamin D and vitamin E showed insufficient. The qualitative profile of dietary consumption is monotonous showing a over recommendation value of dairy and sweets/sugars. There was a significant difference for delayed vaccines (p=0,000), BMI/age (p=0,022), hemoglobin (p=0,031), haematocrit (p=0,011) and pre-albumin (p=0,024) in age from six and 24 months. The diet consumption showed a significant difference among age groups for the energetic value (p=0,002), calcium (p=0.005), folate (p=0.015), vitamin D (p=0.011), vitamin E (p=0.005), cereal group (p=0.002) and group of meat and eggs (p=0.033), were detected that the diet impairment was concentrated in children 25-76 months. There was inadequate intake of the group of meat and eggs too in children six and 24 months. Conclusions: Malnutrition affecting the weight, the levels of pre-albumin and anemia was present in children six to 24 months. The inadequate food consumption was striking feature in children 25-76 months. Thus, it is essential to the continuous multidisciplinary follow-up children with hydrocephalus. / A hidrocefalia é uma patologia complexa que pode apresentar diversas manifestações clínicas com comprometimento no crescimento e desenvolvimento. Os riscos de complicações como processos infecciosos e comprometimento do sistema imunológico podem apresentar-se acentuados na presença de desequilíbrios nutricionais. Porém, são escassos os estudos avaliando o estado nutricional e desequilíbrios nutricionais em crianças com hidrocefalia. Objetivo: Descrever o perfil nutricional de crianças com hidrocefalia. Métodos: Trata-se de um estudo transversal, desenvolvido no Ambulatório de Neurocirurgia do Hospital Universitário no Estado de Sergipe, no período de agosto de 2010 a maio de 2011. Foram coletados dados referentes às condições sócio-econômicas, de saúde, antropometria, exames laboratoriais e consumo alimentar. Resultados: Os resultados demonstraram que das 35 crianças estudadas, 17,1% apresentaram baixo peso, 31,4% quadro de desnutrição com comprometimento do crescimento linear, 40,0% anemia e 37,2% níveis abaixo da referência para pré-albumina. O consumo de energia, lipídios, cálcio, ácido fólico, vitamina D e vitamina E revelou-se insuficiente. O padrão qualitativo do consumo dietético é monótono, apresentando-se acima das recomendações para os grupos dos laticínios e açúcares/doces. Foi encontrada uma diferença significativa para vacinas atrasadas (p=0,000), índice de massa corporal/Idade (IMC/I) (p=0,022), hemoglobina (p=0,031), hematócrito (p=0,011) e pré-albumina (p=0,024) na faixa etária de seis a 24 meses. Excesso de peso estava presente nas crianças de 25 a 76 meses. O consumo dietético apresentou diferença significativa entre as faixas etárias para valor energético (p=0,002), cálcio (p=0,005), ácido fólico (p=0,015), vitamina D (p=0,011), vitamina E (p=0,005), grupo dos cereais (p=0,002) e grupo das carnes e ovos (p=0,033), sendo detectado que o comprometimento dietético estava concentrado nas crianças de 25 a 76 meses. Havia inadequação de consumo do grupo das carnes e ovos também nas crianças de seis a 24 meses. Conclusões: A desnutrição com repercussão no peso, nos níveis de pré-albumina e anemia estava presente nas crianças de seis a 24 meses. O consumo alimentar inadequado foi característica marcante nas crianças de 25 a 76 meses. Dessa forma, torna-se imprescindível o acompanhamento multidisciplinar contínuo nas crianças com hidrocefalia.

This thesis describes the work that I have carried out in the Laboratory of Neurophysiolgy at the Université Libre de Bruxelles, under the supervision of Prof. Serge Schiffmann, in collaboration with Prof. Stéphane Schurmans of Université of Liège.The work is divided in two distinct but related projects and the results section is thus divided into two main chapters. The results described are presented in the form of two manuscripts, the first chapter is named “Ciliary phosphoinositides regulation by INPP5E controls Shh signaling by allowing trafficking of Gpr161 in neural stem cells primary cilium”.The second is named “Regulation of phosphoinositides ciliary levels controls trafficking and ciliogenesis in ependymal cells”.Since both manuscripts are comprehensive regarding the results, and methods, these are inserted as such into the thesis.An expanded introduction to the field, placing the results into context, precedes these two chapters. An extended discussion section follows each chapter; it presents some elements of discussion not included in the manuscripts, the implications of the results and the scope for further research. / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

Retrospektiv wurden das stationäre Kurzzeit-Outcome, Komorbiditäten sowie das 2-Jahres-Outcome von Frühgeborenen (Schwangerschaftswoche < 32, geboren zwischen 1998 - 2016) mit intraventrikulärer Hirnblutung und daraus resultierender Hydrocephalus-Entwicklung am Universitätsklinikum Leipzig untersucht. Diese Kinder wurden 2 Gruppen gegenübergestellt - Frühgeborene mit niedriggradiger Hirnblutung (°I-II) ohne Hydrocephalus und cerebral unauffällige Kinder. Die Auswertung erbrachte für die Hydrocephalus-Gruppe signifikant erhöhte Mortalität und Komorbiditäten, auch das kognitive und motorische Bayley-Outcome nach 2 Jahren war stark eingeschränkt. Hingegen die Kinder mit milder Hirnblutung ohne Hydrocephalus zeigten bei leicht erhöhter Komorbiditätsrate jedoch ein ebenbürtiges 2-Jahres-Outcome, verglichen mit der cerebral unauffälligen Gruppe. An dieser Stelle werden weiterführende, prospektive Multicenter-Studien zur Evaluierung des Sachverhaltes empfohlen.:I Bibliographische Beschreibung II Abkürzungsverzeichnis 1 Einleitung 2 Zielstellung 3 Material und Methoden 3.1 Kollektiv 3.2 Parameter-/Datenaufnahme 3.3 Diagnostik 3.4 Statistische Auswertung 4 Ergebnisse 4.1 Basisdaten aller Kinder bei Geburt und Entlassung 4.2 stationäres Outcome aller Kinder 4.3 Bayley-Outcome aller Kinder 4.4 Subgruppenanalyse PHHC ± IVH °IV 4.4.1 Vergleich der Basisdaten 4.4.2 stationäres Outcome 4.5 Subgruppenanalyse: ELBW 4.5.1 stationäres Outcome verglichen nach Geburtsgewicht: ELBW und ≥ 1000 g 4.5.2 Basisdaten und Outcome für ELBW 4.6 Subgruppenanalyse: Geschlecht 4.7 Subgruppenanalyse: Geburtsjahr vor / nach 2009 4.8 Subgruppenanalyse: Therapie mit rekombinantem, aktiviertem Faktor VII (rFVIIa) 4.9 Subgruppenanalyse: VPS ja / nein 4.10 Subgruppenanalyse: Therapie-Option Lavage 4.10.1 Basisdaten 4.10.2 stationäres Outcome 4.10.3 Bayley-Outcome 4.11 Zusammenfassung der Ergebnisse 5 Diskussion 6 Zusammenfassung Literaturverzeichnis Tabellenverzeichnis Selbstständigkeitserklärung Erklärung über die Vorbehaltlichkeit Lebenslauf Danksagung