Abstract Objective Cranioplasty is routinely performed in neurosurgery. One of its underestimated problems is the high postoperative complication rate of up to 40%. Due to the lack of good prospective studies and the low number of patients (5–20 each year) receiving alloplastic materials, decisions in favor or against a certain material are based on subjective empirical or eco-nomic reasons. The main goal of this first prospective, randomized multicenter study in Germany of custom-made titanium and hydroxyapatite (HA) implants was to compare lo-cal and systemic infections related to the implant within the first six months after implanta-tion. Secondary objectives included comparing reoperation rates, the complication rate, clinical and neurological outcome, and health-related quality of life. Methods The study included patient screening and randomization 6–8 weeks before operation, pre-, intra and postoperative documentation until discharge, and postoperative follow-ups after one and six months. Approval for the study was obtained from the local ethics committee. The study design was published on www.clinicaltrials.gov. Results A total of 52 patients were included in the study. The rate of local, implant associated wound infection in the HA group was 2 out of 26 (7.7%) patients and 5 out of 24 (20.8%) patients in the titanium group (p=0.407 n.s.). Systemic inflammation within six months after operation affected none of the patients in the HA group and 4 out of 24 (37.5%) pa-tients in the titanium group (p=0.107 n.s.). In both groups, 7 patients had to be reoperated after the six-month follow-up (26.9% in the HA group and 29.2% in the titanium group; n.s.). Re-surgery with explantation was necessary in 3 patients in each group (11.5% in the HA group and 12.5% in the titanium group; n.s.). The results demonstrated a significantly higher number of epidural hematomas in the HA group compared to none in the titanium group. Altogether, 46 AE were measured in 27 patients (54%). An improvement of the neurologi-cal outcome after six months was experienced by 43% of the patients in the HA group and 26.3% in the titanium group (p=0.709 n.s.). Conclusion The study emphasizes that cranioplasty is a high-risk intervention. Compared to tita-nium, HA shows a benefit in the infection rate and the neurological outcome, but has at the same time a higher postoperative risk for epidural hematoma. Depending on the individual conditions both materials have their place in future therapy of cranioplasty.

Introdução: Defeitos no crânio e anormalidades ósseas craniofaciais que requerem reconstrução são comuns em uma ampla variedade de procedimentos neurocirúrgicos. Os estudos nessa área têm sido centrados nas complicações e no desenvolvimento de novos materiais e muito pouco no impacto social, na qualidade de vida e na reinserção no mercado de trabalho dos pacientes com falha craniana. Do ponto de vista do paciente, a principal razão para reparação desses defeitos pode ser estética. Os defeitos cranianos são desfigurantes. Os pacientes apresentam dificuldades de adaptação social, isolamento, vergonha, já que são considerados portadores de doenças neurológicas e intelectualmente deficientes, para o grande público. Além disso, o osso craniano fornece importante estrutura de apoio e proteção, restaurando a normalidade da dinâmica do fluxo liquórico, corrigindo os efeitos da pressão atmosférica e melhorando a perfusão e o fluxo sanguíneo cerebral. Objetivos: Avaliar cognição, às atividades da vida diária, a qualidade de vida, os índices de ansiedade e depressão, o retorno ao trabalho, a satisfação com o procedimento e as complicações cirúrgicas após correção de defeitos no crânio. Material e Métodos: Conduziu-se um estudo primário, analítico, intervencional, clinico, longitudinal e prospectivo com 62 pacientes portadores de falhas cranianas que reconstruidas com polimetilmetacrilato impregnado com antibióticos e osso autólogo. Avaliou-se com essa cranioplastia tardia, nos tempos pré-operatório, 3, 6, 12 e 24 meses, a melhora cognitiva através do Miniexame do Estado Mental, a evolução motora e das atividades da vida diária pelas escalas de Barthel e Rankin, a qualidade de vida relacionada à saúde pelo SF-36; os índices de ansiedade e depressão pela escala HAD; o retorno às atividades laborais, a satisfação com o procedimento e suas complicações. Resultados: A amostra estudada mostrou uma média de idade de 40 anos, predomínio do sexo masculino (77%), raça branca e mais de 5 anos de escolaridade (85%). A causa da craniectomia descompressiva foi predominante por acidentes (58%) e agressões (22,6%); 6 pacientes sofreram AVC (9,6%). A média do escores de Glasgow da admissão foi 9 ± 3. A craniectomia descompressiva foi realizada no lado direito em 47% dos pacientes e em 39% no lado esquerdo do crânio. Politrauma ocorreu em 16 % dos pacientes. O tamanho médio da falha craniana foi de 127,5 ± 34,1 cm2. Apresentavam falha considerada moderada e grande 91% dos pacientes. A média em meses do trauma até a realização da cranioplastia foi de 25 ± 15 meses. Houve melhora da cognição ao final de 12 meses (p=0,002); 57% dos pacientes melhoraram pelo menos 5 pontos nas escalas das atividades da vida diária. Todos os parâmetros da qualidade de vida melhoraram (p<0,001). A melhora no estado geral de saúde tornou-se significativa já no terceiro mês de pós-operatório; os aspectos sociais e a vitalidade tornaram-se significativos aos 6 meses; os demais parâmetros aos 12 meses e mantiveram-se aos 24 meses. A pontuação para depressão foi reduzida já no terceiro mês de pós-operatório, reduziu ainda mais aos 12 meses e se manteve aos 24 meses, (p<0,001). A ansiedade reduziu aos 12 meses de pós-operatório, mantendo-se assim aos 24 meses, (p<0,001). Cinquenta e três por cento dos pacientes exerciam alguma atividade laboral aos 12 meses após a cranioplastia; 92% estavam satisfeitos com o procedimento e os índices de infecção foram de 3,2%. Conclusão: Nesta amostra observamos melhora na cognição, na qualidade de vida, nos sintomas ansiosos e depressivos e reintrodução dos pacientes no mercado de trabalho. A reconstrução com polimetilmetacrilato impregnado com antibióticos mostrou-se segura e eficaz com baixos índices de complicações infecciosas. / Introduction: Skull defects and craniofacial bone abnormalities that require bone reconstruction are common in a wide range of neurosurgical procedures. The studies on the subject have been much more focused on the complications and development of new materials rather than on the social impact, the quality of life and re-entrance into the labor market by patients with skull defects. From the patients’ point of view, the main reason for the repair of these defects may be cosmetic, because skull defects are disfiguring. The patients present difficulties for social adaptation, isolation, embarrassment, and are considered by the general public as having neurologically diseases and intellectual impairments. But, in addition, the cranial bone provides an important structure for support and protection, restoring the normality of the cerebrospinal fluid flow, correcting the effects of atmospheric pressure and improving perfusion and cerebral blood flow. Objectives: To evaluate cognitive response, response to daily routine activities, quality of life, rates of anxiety and depression, return to work, satisfaction with the procedure and surgical complications after correction of skull defects. Materials and Methods: We performed a primary, analytical, interventional, clinical, longitudinal, prospective, noncontrolled study with 62 patients with skull defects, performing a late reconstruction with antimicrobial-impregnated PMMA and autologous bone. We evaluated the cognitive improvement through the mental state mini-exam; development of motor skills and daily life activities though Barthel and Rankin scale; health-related quality of life through SF-36; anxiety and depression indexes through the HAD scale; return to work activities; satisfaction with the procedure and its complications in the preoperative period, 3, 6, 12, and 24 months postoperatively. Results: The sample presented an average age of 40 years, most of them male (77%), white and with more than 5 years of education (85%). The cause of decompressive craniectomy (DC) was mostly accidents (58%) and aggressions (22.6%); 6 patients suffered a stroke (9.6%). The average Glasgow at admission was low, 9 ± 3. The DC was performed on the right side in 47% of patients and 39% on the left side of the skull. Multiple trauma occurred in 16% of patients. The average size of the skull defect was 127.5 ± 34.1 cm2. 91% of the patients presented moderate or large defect. The average time between the trauma and cranioplasty was 25 ± 15 months. There was an improvement in cognition after 12 months (p=0.002); 57% of patients improved at least 5 points on the daily life activities scales. All life quality parameters improved (p<0.001). An improvement in general health state became significant by the third month after surgery; in the social aspects and vitality became significant at 6 months; in the other parameters became significant at 12 months and stayed significant at 24 months. The scores for depression were reduced on the third month after surgery, further reduced at 12 months and remained still at 24 months, p<(0.001). Anxiety was reduced at 12 months after surgery, staying still at 24 months (p<0.001). 53% percent of patients performed some sort of work activity at 12 months after cranioplasty; 92% were satisfied with the procedure and infection rates were 3.2%. Conclusion: Cranioplasty improves cognition, quality of life, symptoms of anxiety and depression and reintroduces patients to the labor market. The reconstruction with antimicrobial-impregnated PMMA proved safe and effective with low rates of infectious complications.

Orientador: Aristides Augusto Palhares Neto / Resumo: RESUMO GONÇALVES M. P. Cranioplastia Com Implante Prototipado – Uma Revisão Sistemática e Metanálise Proporcional. 2018. 67. Dissertação (Mestrado) - Faculdade de Medicina de Botucatu, Universidade Estadual Paulista “Júlio de Mesquita Filho”, Botucatu, 2018. Introdução: com o avanço tecnológico e popularização de softwares e impressoras 3D, cranioplastias com implantes aloplásticos prototipados tornaram-se mais uma ferramenta para correção de falhas ósseas secundárias a craniectomias. Assim, seu uso cada vez mais comum, abre uma área com necessidade de maiores estudos e discussões. Objetivos: revisar os artigos da literatura referentes a cranioplastia com implantes prototipados 3D em pacientes submetidos a craniectomia descompressiva secundários à trauma, acidente vascular encefálico hemorrágico e pós ressecção tumoral Métodos: Realizou-se uma revisão literária buscando artigos com descritores controlados nas bases de dados Medical Literature Analisys And Retrievel Sistem Online (MedLine), Biblioteca Virtual em Saúde (BVS), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e Scientifc Eletronic Library Online (SciELO). Realizaram-se todas as combinações possíveis entre os descritores em cada base de dados, utilizando-se o conector booleando “AND”. Assim, foram encontrados 185 artigos, sendo 114 na base de dados da Medline, 71 na BVS e nenhum na LILACS e SciELO. Dentre um levantamento de dados de estudos de séries de casos foi montada a TABELA BASE, na qual... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Cranioplasties with prototyped alloplastic implants have become another tool for bone defects corrections due to craniectomies on account of technological advancement and popularization of software and 3D printers. Because of its increasing common use, there is a need of further studies and discussions. Objectives: To review literature articles on cranioplasty with 3D prototyped implants in patients submitted to decompressive craniectomy secondary to trauma, hemorrhagic encephalic stroke and post tumor resection. Methods: A literature review was carried out to search for articles with descriptors controlled in the Medical Literature Analyzes and Retrieve Sistem Online (MedLine), Virtual Health Library (VHL), Latin American and Caribbean Literature in Health Sciences (LILACS) and Scientifc Eletronic Library Online (SciELO). All possible combinations between the descriptors in each database were made using the "AND" boolean connector. Thus, 185 articles were found, 114 in the Medline database, 71 in the VHL, and none in LILACS and SciELO. From a data collection of case series studies, we assembled the BASE TABLE, in which the test used to perform the statistical comparisons was the Normality Test. Results: Fourteen selected articles were published until March 2017. All of them were case series. In the statistical analysis, infection Np versus infection Na versus infection Nt the value is p = 0.7044; the incidence of exposure of the Np cranioplasty material versus ... (Complete abstract click electronic access below) / Mestre

Introdução: Defeitos no crânio e anormalidades ósseas craniofaciais que requerem reconstrução são comuns em uma ampla variedade de procedimentos neurocirúrgicos. Os estudos nessa área têm sido centrados nas complicações e no desenvolvimento de novos materiais e muito pouco no impacto social, na qualidade de vida e na reinserção no mercado de trabalho dos pacientes com falha craniana. Do ponto de vista do paciente, a principal razão para reparação desses defeitos pode ser estética. Os defeitos cranianos são desfigurantes. Os pacientes apresentam dificuldades de adaptação social, isolamento, vergonha, já que são considerados portadores de doenças neurológicas e intelectualmente deficientes, para o grande público. Além disso, o osso craniano fornece importante estrutura de apoio e proteção, restaurando a normalidade da dinâmica do fluxo liquórico, corrigindo os efeitos da pressão atmosférica e melhorando a perfusão e o fluxo sanguíneo cerebral. Objetivos: Avaliar cognição, às atividades da vida diária, a qualidade de vida, os índices de ansiedade e depressão, o retorno ao trabalho, a satisfação com o procedimento e as complicações cirúrgicas após correção de defeitos no crânio. Material e Métodos: Conduziu-se um estudo primário, analítico, intervencional, clinico, longitudinal e prospectivo com 62 pacientes portadores de falhas cranianas que reconstruidas com polimetilmetacrilato impregnado com antibióticos e osso autólogo. Avaliou-se com essa cranioplastia tardia, nos tempos pré-operatório, 3, 6, 12 e 24 meses, a melhora cognitiva através do Miniexame do Estado Mental, a evolução motora e das atividades da vida diária pelas escalas de Barthel e Rankin, a qualidade de vida relacionada à saúde pelo SF-36; os índices de ansiedade e depressão pela escala HAD; o retorno às atividades laborais, a satisfação com o procedimento e suas complicações. Resultados: A amostra estudada mostrou uma média de idade de 40 anos, predomínio do sexo masculino (77%), raça branca e mais de 5 anos de escolaridade (85%). A causa da craniectomia descompressiva foi predominante por acidentes (58%) e agressões (22,6%); 6 pacientes sofreram AVC (9,6%). A média do escores de Glasgow da admissão foi 9 ± 3. A craniectomia descompressiva foi realizada no lado direito em 47% dos pacientes e em 39% no lado esquerdo do crânio. Politrauma ocorreu em 16 % dos pacientes. O tamanho médio da falha craniana foi de 127,5 ± 34,1 cm2. Apresentavam falha considerada moderada e grande 91% dos pacientes. A média em meses do trauma até a realização da cranioplastia foi de 25 ± 15 meses. Houve melhora da cognição ao final de 12 meses (p=0,002); 57% dos pacientes melhoraram pelo menos 5 pontos nas escalas das atividades da vida diária. Todos os parâmetros da qualidade de vida melhoraram (p<0,001). A melhora no estado geral de saúde tornou-se significativa já no terceiro mês de pós-operatório; os aspectos sociais e a vitalidade tornaram-se significativos aos 6 meses; os demais parâmetros aos 12 meses e mantiveram-se aos 24 meses. A pontuação para depressão foi reduzida já no terceiro mês de pós-operatório, reduziu ainda mais aos 12 meses e se manteve aos 24 meses, (p<0,001). A ansiedade reduziu aos 12 meses de pós-operatório, mantendo-se assim aos 24 meses, (p<0,001). Cinquenta e três por cento dos pacientes exerciam alguma atividade laboral aos 12 meses após a cranioplastia; 92% estavam satisfeitos com o procedimento e os índices de infecção foram de 3,2%. Conclusão: Nesta amostra observamos melhora na cognição, na qualidade de vida, nos sintomas ansiosos e depressivos e reintrodução dos pacientes no mercado de trabalho. A reconstrução com polimetilmetacrilato impregnado com antibióticos mostrou-se segura e eficaz com baixos índices de complicações infecciosas. / Introduction: Skull defects and craniofacial bone abnormalities that require bone reconstruction are common in a wide range of neurosurgical procedures. The studies on the subject have been much more focused on the complications and development of new materials rather than on the social impact, the quality of life and re-entrance into the labor market by patients with skull defects. From the patients’ point of view, the main reason for the repair of these defects may be cosmetic, because skull defects are disfiguring. The patients present difficulties for social adaptation, isolation, embarrassment, and are considered by the general public as having neurologically diseases and intellectual impairments. But, in addition, the cranial bone provides an important structure for support and protection, restoring the normality of the cerebrospinal fluid flow, correcting the effects of atmospheric pressure and improving perfusion and cerebral blood flow. Objectives: To evaluate cognitive response, response to daily routine activities, quality of life, rates of anxiety and depression, return to work, satisfaction with the procedure and surgical complications after correction of skull defects. Materials and Methods: We performed a primary, analytical, interventional, clinical, longitudinal, prospective, noncontrolled study with 62 patients with skull defects, performing a late reconstruction with antimicrobial-impregnated PMMA and autologous bone. We evaluated the cognitive improvement through the mental state mini-exam; development of motor skills and daily life activities though Barthel and Rankin scale; health-related quality of life through SF-36; anxiety and depression indexes through the HAD scale; return to work activities; satisfaction with the procedure and its complications in the preoperative period, 3, 6, 12, and 24 months postoperatively. Results: The sample presented an average age of 40 years, most of them male (77%), white and with more than 5 years of education (85%). The cause of decompressive craniectomy (DC) was mostly accidents (58%) and aggressions (22.6%); 6 patients suffered a stroke (9.6%). The average Glasgow at admission was low, 9 ± 3. The DC was performed on the right side in 47% of patients and 39% on the left side of the skull. Multiple trauma occurred in 16% of patients. The average size of the skull defect was 127.5 ± 34.1 cm2. 91% of the patients presented moderate or large defect. The average time between the trauma and cranioplasty was 25 ± 15 months. There was an improvement in cognition after 12 months (p=0.002); 57% of patients improved at least 5 points on the daily life activities scales. All life quality parameters improved (p<0.001). An improvement in general health state became significant by the third month after surgery; in the social aspects and vitality became significant at 6 months; in the other parameters became significant at 12 months and stayed significant at 24 months. The scores for depression were reduced on the third month after surgery, further reduced at 12 months and remained still at 24 months, p<(0.001). Anxiety was reduced at 12 months after surgery, staying still at 24 months (p<0.001). 53% percent of patients performed some sort of work activity at 12 months after cranioplasty; 92% were satisfied with the procedure and infection rates were 3.2%. Conclusion: Cranioplasty improves cognition, quality of life, symptoms of anxiety and depression and reintroduces patients to the labor market. The reconstruction with antimicrobial-impregnated PMMA proved safe and effective with low rates of infectious complications.

Introdução: Defeitos no crânio e anormalidades ósseas craniofaciais que requerem reconstrução são comuns em uma ampla variedade de procedimentos neurocirúrgicos. Os estudos nessa área têm sido centrados nas complicações e no desenvolvimento de novos materiais e muito pouco no impacto social, na qualidade de vida e na reinserção no mercado de trabalho dos pacientes com falha craniana. Do ponto de vista do paciente, a principal razão para reparação desses defeitos pode ser estética. Os defeitos cranianos são desfigurantes. Os pacientes apresentam dificuldades de adaptação social, isolamento, vergonha, já que são considerados portadores de doenças neurológicas e intelectualmente deficientes, para o grande público. Além disso, o osso craniano fornece importante estrutura de apoio e proteção, restaurando a normalidade da dinâmica do fluxo liquórico, corrigindo os efeitos da pressão atmosférica e melhorando a perfusão e o fluxo sanguíneo cerebral. Objetivos: Avaliar cognição, às atividades da vida diária, a qualidade de vida, os índices de ansiedade e depressão, o retorno ao trabalho, a satisfação com o procedimento e as complicações cirúrgicas após correção de defeitos no crânio. Material e Métodos: Conduziu-se um estudo primário, analítico, intervencional, clinico, longitudinal e prospectivo com 62 pacientes portadores de falhas cranianas que reconstruidas com polimetilmetacrilato impregnado com antibióticos e osso autólogo. Avaliou-se com essa cranioplastia tardia, nos tempos pré-operatório, 3, 6, 12 e 24 meses, a melhora cognitiva através do Miniexame do Estado Mental, a evolução motora e das atividades da vida diária pelas escalas de Barthel e Rankin, a qualidade de vida relacionada à saúde pelo SF-36; os índices de ansiedade e depressão pela escala HAD; o retorno às atividades laborais, a satisfação com o procedimento e suas complicações. Resultados: A amostra estudada mostrou uma média de idade de 40 anos, predomínio do sexo masculino (77%), raça branca e mais de 5 anos de escolaridade (85%). A causa da craniectomia descompressiva foi predominante por acidentes (58%) e agressões (22,6%); 6 pacientes sofreram AVC (9,6%). A média do escores de Glasgow da admissão foi 9 ± 3. A craniectomia descompressiva foi realizada no lado direito em 47% dos pacientes e em 39% no lado esquerdo do crânio. Politrauma ocorreu em 16 % dos pacientes. O tamanho médio da falha craniana foi de 127,5 ± 34,1 cm2. Apresentavam falha considerada moderada e grande 91% dos pacientes. A média em meses do trauma até a realização da cranioplastia foi de 25 ± 15 meses. Houve melhora da cognição ao final de 12 meses (p=0,002); 57% dos pacientes melhoraram pelo menos 5 pontos nas escalas das atividades da vida diária. Todos os parâmetros da qualidade de vida melhoraram (p<0,001). A melhora no estado geral de saúde tornou-se significativa já no terceiro mês de pós-operatório; os aspectos sociais e a vitalidade tornaram-se significativos aos 6 meses; os demais parâmetros aos 12 meses e mantiveram-se aos 24 meses. A pontuação para depressão foi reduzida já no terceiro mês de pós-operatório, reduziu ainda mais aos 12 meses e se manteve aos 24 meses, (p<0,001). A ansiedade reduziu aos 12 meses de pós-operatório, mantendo-se assim aos 24 meses, (p<0,001). Cinquenta e três por cento dos pacientes exerciam alguma atividade laboral aos 12 meses após a cranioplastia; 92% estavam satisfeitos com o procedimento e os índices de infecção foram de 3,2%. Conclusão: Nesta amostra observamos melhora na cognição, na qualidade de vida, nos sintomas ansiosos e depressivos e reintrodução dos pacientes no mercado de trabalho. A reconstrução com polimetilmetacrilato impregnado com antibióticos mostrou-se segura e eficaz com baixos índices de complicações infecciosas. / Introduction: Skull defects and craniofacial bone abnormalities that require bone reconstruction are common in a wide range of neurosurgical procedures. The studies on the subject have been much more focused on the complications and development of new materials rather than on the social impact, the quality of life and re-entrance into the labor market by patients with skull defects. From the patients’ point of view, the main reason for the repair of these defects may be cosmetic, because skull defects are disfiguring. The patients present difficulties for social adaptation, isolation, embarrassment, and are considered by the general public as having neurologically diseases and intellectual impairments. But, in addition, the cranial bone provides an important structure for support and protection, restoring the normality of the cerebrospinal fluid flow, correcting the effects of atmospheric pressure and improving perfusion and cerebral blood flow. Objectives: To evaluate cognitive response, response to daily routine activities, quality of life, rates of anxiety and depression, return to work, satisfaction with the procedure and surgical complications after correction of skull defects. Materials and Methods: We performed a primary, analytical, interventional, clinical, longitudinal, prospective, noncontrolled study with 62 patients with skull defects, performing a late reconstruction with antimicrobial-impregnated PMMA and autologous bone. We evaluated the cognitive improvement through the mental state mini-exam; development of motor skills and daily life activities though Barthel and Rankin scale; health-related quality of life through SF-36; anxiety and depression indexes through the HAD scale; return to work activities; satisfaction with the procedure and its complications in the preoperative period, 3, 6, 12, and 24 months postoperatively. Results: The sample presented an average age of 40 years, most of them male (77%), white and with more than 5 years of education (85%). The cause of decompressive craniectomy (DC) was mostly accidents (58%) and aggressions (22.6%); 6 patients suffered a stroke (9.6%). The average Glasgow at admission was low, 9 ± 3. The DC was performed on the right side in 47% of patients and 39% on the left side of the skull. Multiple trauma occurred in 16% of patients. The average size of the skull defect was 127.5 ± 34.1 cm2. 91% of the patients presented moderate or large defect. The average time between the trauma and cranioplasty was 25 ± 15 months. There was an improvement in cognition after 12 months (p=0.002); 57% of patients improved at least 5 points on the daily life activities scales. All life quality parameters improved (p<0.001). An improvement in general health state became significant by the third month after surgery; in the social aspects and vitality became significant at 6 months; in the other parameters became significant at 12 months and stayed significant at 24 months. The scores for depression were reduced on the third month after surgery, further reduced at 12 months and remained still at 24 months, p<(0.001). Anxiety was reduced at 12 months after surgery, staying still at 24 months (p<0.001). 53% percent of patients performed some sort of work activity at 12 months after cranioplasty; 92% were satisfied with the procedure and infection rates were 3.2%. Conclusion: Cranioplasty improves cognition, quality of life, symptoms of anxiety and depression and reintroduces patients to the labor market. The reconstruction with antimicrobial-impregnated PMMA proved safe and effective with low rates of infectious complications.

Severe traumatic brain injury (sTBI) is a cause of death and disability worldwide and requires treatment at specialized neuro-intensive care units (NICU) with a multimodal monitoring approach. The CT scan imaging supports the monitoring and diagnostics. The level of S100B and neuron specific enolase (NSE) reflects the severity of the injury. The therapy resistant intracranial hypertension requires decompressive craniectomy (DC). After DC, the cranium must be reconstructed to recreate the normal intracranial physiology as well as to address cosmetic issues. The evolution of the pathological intracranial changes was analyzed in accordance with the three CT classifications: Marshall, Rotterdam and Morris-Marshall. The Rotterdam scale was best in describing the dynamics of the pathological evolution. Both the Rotterdam score and Morris- Marshall classification showed strong correlation with the clinical outcome, a finding that suggests that they could be used for prognostication. We demonstrated a clear correlation between the CT classifications and concentrations of S100B and NSE. The results revealed a concomitant correlation between NSE and S100B and clinical outcome. We found that the interaction between the ICP, Rotterdam CT classification, and concentrations of biochemical biomarkers are all associated with DC. We found a high percentage of complications following cranioplasty. Our results call into question whether custom-made allograft should be considered the best material for cranioplasty. It is concluded that both the Rotterdam and Morris-Marshall classification contribute to clinical evaluation of intracranial dynamics after sTBI, and might be used in combination with biochemical biomarkers for better assessment. The decision to perform DC should include a re-assesment of ICP evolution, CT scan images and concentration of the biochemical biomarkers. Furthermore, when determining whether DC treatment should be used, surgeon should also consider the risks of the following cranioplasty.

Abstract Objective Cranioplasty is routinely performed in neurosurgery. One of its underestimated problems is the high postoperative complication rate of up to 40%. Due to the lack of good prospective studies and the low number of patients (5–20 each year) receiving alloplastic materials, decisions in favor or against a certain material are based on subjective empirical or eco-nomic reasons. The main goal of this first prospective, randomized multicenter study in Germany of custom-made titanium and hydroxyapatite (HA) implants was to compare lo-cal and systemic infections related to the implant within the first six months after implanta-tion. Secondary objectives included comparing reoperation rates, the complication rate, clinical and neurological outcome, and health-related quality of life. Methods The study included patient screening and randomization 6–8 weeks before operation, pre-, intra and postoperative documentation until discharge, and postoperative follow-ups after one and six months. Approval for the study was obtained from the local ethics committee. The study design was published on www.clinicaltrials.gov. Results A total of 52 patients were included in the study. The rate of local, implant associated wound infection in the HA group was 2 out of 26 (7.7%) patients and 5 out of 24 (20.8%) patients in the titanium group (p=0.407 n.s.). Systemic inflammation within six months after operation affected none of the patients in the HA group and 4 out of 24 (37.5%) pa-tients in the titanium group (p=0.107 n.s.). In both groups, 7 patients had to be reoperated after the six-month follow-up (26.9% in the HA group and 29.2% in the titanium group; n.s.). Re-surgery with explantation was necessary in 3 patients in each group (11.5% in the HA group and 12.5% in the titanium group; n.s.). The results demonstrated a significantly higher number of epidural hematomas in the HA group compared to none in the titanium group. Altogether, 46 AE were measured in 27 patients (54%). An improvement of the neurologi-cal outcome after six months was experienced by 43% of the patients in the HA group and 26.3% in the titanium group (p=0.709 n.s.). Conclusion The study emphasizes that cranioplasty is a high-risk intervention. Compared to tita-nium, HA shows a benefit in the infection rate and the neurological outcome, but has at the same time a higher postoperative risk for epidural hematoma. Depending on the individual conditions both materials have their place in future therapy of cranioplasty.

Made available in DSpace on 2015-03-26T13:47:13Z (GMT). No. of bitstreams: 1 texto completo.pdf: 2356825 bytes, checksum: d31053454fc83d68df0097e746529fd9 (MD5) Previous issue date: 2013-02-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The loss of bone tissue is an important problem both in human and in veterinary medicines. For cranial bone defects, surgical intervention is necessary since, if not correct, these defects result in high number of cerebral lesions and neurological dysfunctions as well as esthetic sequelae. In such context, autogenous and alogenous grafts have given place to resorbable osteoconductive biomaterials. The objective of the present study was to evaluate a bone cement made from a solid phase (&#946;-tricalcium phosphate and calcium sulfate dihydrate) and a liquid one (phosphoric acid 2M). These components were mixed in a stainless steel cube at a proportion of 1:1 and the material while still moldable, was applied in 15mm critical size defects in the cranial bone of rabbits, Scanning electron microscopy of the cement itself showed a complex surface with non-interconnected pores of 19.5±5.92 &#956;m in diameter. Animals were separated in three experimental moments based on the time after surgical procedure (7, 28 and 90 days), comparing to defects that did not receive the material. Hematological and serum biochemistry revealed normal values during the entire experiment. Dehiscence, edema or signs of infection were not observed. In treated animals, alterations were observed on skin (hyperemia and necrosis) and brain (circular lesions of green color with vascular congestion) that evolved to healing at 90 days. These alterations may be related related to a low pH of the biomaterial during the implantation (3.38), resulted from the proportion of liquid:powder used in the present study (1:1). As suggested by computerized tomography and confirmed by histology, new bone formation occurred in control group from the margin of the defect and inside it. In treated group, bone growth was apparently less intense at 90 days when compared to the control one, limited to the margin of the defect and not observed inside it. Osteointegration was confirmed and neither signs of undesirable chronic inflammation nor the formation of a fibrous capsule around the material was observed. Thereby, the biomaterial was characterized as osteoconductor, osteointegrated, degradable in vivo and histologically biocompatible. The alterations in the color of nervous tissue and skin adjacent to the implant, although with no clinical relevance, indicate the need for a modification on the proportion of the biomaterial components. Possibly, reducing the relation liquid:powder may allow its application. / A perda de tecido ósseo é um problema grave tanto na medicina humana quanto na veterinária. No caso das falhas ósseas cranianas, a intervenção cirúrgica se faz necessária porque, se não forem corrigidas, provocam altos índices de lesões cerebrais e disfunções neurológicas, bem como graves sequelas estéticas. Nesse contexto, enxertos autógenos e alógenos têm sido substituídos por biomateriais osteocondutores e reabsorvíeis. O objetivo desse trabalho foi avaliar a utilização de um cimento ósseo formulado a partir de uma fase sólida (&#946;-fosfato tricálcico e sulfato de cálcio di-hidratado) e uma fase líquida (ácido fosfórico 2M). Esses componentes foram misturados na proporção 1:1 e o material, ainda moldável, foi aplicado em defeitos ósseos de tamanho crítico no crânio de coelhos, com 15 mm de diâmetro. A análise do cimento pela microscopia eletrônica de varredura revelou superfície complexa com poros de 19,5 (±5,92) &#956;m não interconectados. Os animais foram divididos em três momentos experimentais com base no tempo transcorrido após o procedimento cirúrgico (sete, 28 e 90 dias), onde os defeitos tratados foram comparados aos defeitos que não receberam o biomaterial. As análises hematológicas e da bioquímica sérica evidenciaram valores normais durante todo o experimento. Não foram observados deiscência, edema ou sinais de infecção. Nos animais tratados, foram observadas alterações na pele (hiperemia e necrose) e no cérebro (lesões circulares de coloração esverdeada com congestão vascular), que evoluíram para a cicatrização aos 90 dias. Essas alterações podem ser atribuídas ao baixo pH do biomaterial no momento de sua implantação (3,38), resultante da relação líquido/pó utilizada no presente trabalho (1:1). Foi sugerido pela tomografia computadorizada e confirmado pela análise histológica crescimento de osso novo, que no grupo controle ocorreu a partir das bordas e no interior do defeito. Já nos animais do grupo tratado esse crescimento foi menor aos 90 dias, quando comparado ao controle na mesma data, e limitou-se às bordas do defeito, não ocorrendo no interior. Foi demonstrada a osteointegração do biomaterial, não sendo observados sinais de inflamação crônica indesejável ou a formação de cápsula fibrosa ao seu redor. Após análise dos dados obtidos o biomaterial foi caracterizado como osteocondutor, osteointegrável, possuindo degradação in vivo e histologicamente biocompatível. As alterações na coloração no tecido nervoso na região do implante, mesmo sem comprometimento clínico, e as lesões de pele, indicam a necessidade de modificação da proporção dos componentes. Possivelmente, a redução da relação líquido/pó viabilizará sua aplicação.

Zranenia hlavy si často vyžadujú lekársku starostlivosť, pri ktorej dochádza k stabilizácii alebo náhrade poškodeného tkaniva. Pre tento účel slúži kranioplastika, ktorá prinavracia pacientovi ochranný a kozmetický výsledok. Výber správneho materiálu kraniálneho implantátu je veľmi podstatný. Naviac potrebuje správny druh fixácie, ktorá ho udrží na mieste a predíde sa tak nedovolenému pohybu implantátu počas bežného života pacienta. Táto práca analyzuje deformačné a napäťové stavy dvoch druhov fixačných plátov prichytených na PMMA implantáte a ich mechanickej odozvy na rozličné záťažné podmienky spôsobené rôznymi stavmi kraniálnej hypertenzie a silou pôsobiacou na sústavu z exteriéru.

Abstract This thesis evaluated the factors affecting bone flap survival and bone flap resorption after primary cranial reparation surgery, cranioplasty, conducted to repair a cranial bone defect with an autologous cryopreserved bone flap. Emphasis is put on the predictors, progression, and definition of an important yet poorly understood postoperative complication, bone flap resorption. Study I assessed the rates and predictors of bone flap removal and bone flap resorption in a Finnish retrospective multicentre setting. 40% of patients developed complications of whom half required bone flap removal. Bone flap resorption and surgical site infections were the underlying cause in 90% of bone flap removal surgeries. The prevalence of both surgical site infections and bone flap resorption was 9%. In summary, young age was found to predict bone flap resorption and smoking predisposed patients to infections requiring bone flap removal. Study II applied computed tomography-based volumetry to evaluate the prevalence of subclinical bone flap resorption and to monitor its progression. In the follow-up, 90% of patients were found to have decreased bone flap volumes indicating varying degrees of resorption. However, the progression of bone flap resorption as a function of follow-up time was non-linear on the cohort level, and thus routine radiological follow-up seems unjustified. Most bone flaps do not appear to resorb enough to require removal even in the long-term follow-up. Study III addressed the unclarity in the definition of bone flap resorption. The computed tomography-based Oulu Resorption Score was developed to standardise the interpretation of radiological bone flap resorption and to guide follow-up interventions. The score values range from 0 to 9 with increasing values implying more severe bone flap resorption. Coupled with radiological evaluation conducted by independent neurosurgeons, an Oulu Resorption Score of ≥5 was defined to be clinically relevant. Further, the scores were divided into four grades based on the recommended follow-up procedures. Grades 0 (score 0) and I (scores 1 to 4) require no additional follow-up, but those with a grade II (score 5 to 8) or III (score 9) should be referred to neurosurgical consultation with reoperation considered at least in cases of grade III bone flap resorption. / Tiivistelmä Tässä väitöstyössä selvitettiin potilaan omalla kylmäsäilytetyllä luuistutteella tehtyjen kallon luupuutosten ensikertaisten korjausleikkausten tuloksiin vaikuttavia tekijöitä. Erityisesti tarkasteltiin luuistutteen liukenemisen, erään tärkeän, joskin heikosti ymmärretyn komplikaation ennustavia tekijöitä, etenemistä ja määritelmää. Tutkimuksessa I selvitettiin luuistutteen poiston ja liukenemisen yleisyyttä ja näihin vaikuttavia tekijöitä suomalaisessa takautuvassa monikeskusaineistossa. Potilaista 40 %:lle kehittyi komplikaatio. Komplikaatioista puolet johti istutteen poistoon. Luuistutteen liukeneminen ja leikkausalueinfektiot muodostivat 90 % poistoon johtaneista komplikaatioista. Sekä infektioiden että istutteen liukenemi¬sen esiintyvyys oli 9 %. Nuori ikä altisti istutteen liukenemiselle ja tupakointi leikkausalueinfektiolle. Tutkimuksessa II sovellettiin tietokonetomografiaan perustuvaa tilavuusmittausta luuistutteen oireettoman liukenemisen esiintyvyyden ja etenemistaipumuksen selvittämiseksi. Seurannassa 90 %:lla potilaista todettiin alentunut luuistutteen tilavuus viitaten asteeltaan vaihtelevaan istutteen liukenemiseen. Koko tutkimusjoukon tasolla istutteiden liukeneminen ei kuitenkaan edennyt lineaarisesti seuranta-ajan funktiona, joten rutiininomainen seuranta kuvantamistutkimuksin ei vaikuta perustellulta. Suurin osa luuistutteista liukeni niin vähän, ettei uutta leikkausta tarvittu pitkässäkään seurannassa. Tutkimuksessa III käsiteltiin luuistutteen liukenemisen nykyisellään epäselvää määritelmää ja kehitettiin uusi tietokonetomografiaan perustuva pisteytysjärjestelmä (Oulu resorption score) tarkoituksena vakioida radiologisten luuistutteen liukenemislöydösten tulkinta ja ohjata hoitolinjan valintaa. Pisteytysarvot vaihtelevat välillä 0-9. Kasvava arvo kuvaa luuistutteen liukenemisen vaikeusasteen kasvua. Luokitus yhdistettiin riippumattomien neurokirurgien radiologisiin arvioihin, joiden perusteella pistemäärä ≥5 määriteltiin kliinisesti merkitykselliseksi. Pistemäärät jaettiin neljään luokkaan suositeltujen jatkotoimenpiteiden mukaisesti. Luokkia 0 (0 pistettä) ja I (1–4 pistettä) vastaava luuistutteen liukeneminen ei vaadi jatkotoimenpiteitä. Luokkia II (5–8 pistettä) ja III (9 pistettä) vastaavasta luuistutteen liukenemisesta suositellaan konsultoitavan neurokirurgia. Uusintaleikkausta suositellaan harkittavan ainakin luokan III tapauksissa.