Forward genetic screens in the mouse are contributing significantly to our understanding of basic mammalian development and human disease. In one such screen, our laboratory has identified the novel mouse gumby mutant, which affects the development of the neural and vascular systems. Here, I describe the characterization of the gumby mutant phenotype and the identification of its causative mutation in a novel, vertebrate-specific gene, which is one of the genes deleted in patients affected by Cri du Chat Syndrome that exhibit mental retardation and craniofacial deficits. Expression and phenotypic analyses revealed a requirement for the gumby gene in the facial nerve axon guidance and angiogenesis. Lately, it has become evident that many common mechanisms and molecules operate during neural and vascular development. My results suggest that the gumby gene is an attractive candidate for regulating both processes and its analysis in the future may help us understand how the navigational mechanisms for both systems are intertwined. My studies show that gumby is a cytoplasmic protein that is present in many embryonic and adult tissues. In yeast-two-hybrid assays gumby interacts with a member of the highly conserved Wnt pathway - Dishevelled 2 (Dvl2). In both Dvl2-/- and gumby homozygotes, the level of the cardiac neural crest cell marker Plexin2A is decreased. The three branches of the Wnt pathway have been shown to regulate a wide range of events during embryogenesis and adult homeostasis, and subsequently have been implicated in multiple human pathologies. Taken together my data suggest that gumby may be required for Wnt signaling in angiogenesis and/or facial nerve guidance. Given that Wnt signaling has been shown to play key roles in axon guidance, gumby and its roles in Wnt signaling may also contribute to the mental retardation seen in patients with Cri du Chat Syndrome. Thus, further analyses of molecular and biologic roles of gumby will provide important avenues for understanding the cell biology of human disease.

Thesis (M. Med (Rad. Diagn.)) --University of Limpopo, Medunsa Campus, 2011 / Objective: The objective was to determine the incidence of missed pathology on normal non contrast enhanced cranial computed tomography (NECT).Method: Records of cranial computed tomography scans done over a 12 month period at the Dr George Mukhari Hospital were evaluated by three readers. The NECT and contrast enhanced cranial computed tomography (CECT) were read at separate occasions and readers did not have access to a history, each other’s interpretation or to their own interpretation of the NECT when the CECT was evaluated. The data was evaluated and analysed after the 3 readers had seen the cases individually. Interpretation discrepancies were resolved during a meeting between all 3 readers and consensus was reached. Cases with missed pathology on the NECT were evaluated retrospectively at a joint meeting between the 3 readers to determine whether the pathology was visible on the NECT and thus to determine the combined reader error rate. Results: In this study 3.28 % of cases had pathology missed by 3 readers on the NECT. Retrospective viewing reduced this to 1.42% indicating a reader error of 1.85%. This incidence of missed pathology correlates with the most recent studies done. Having a thorough medical history of the patient and selecting those with clinical findings indicating the need for a CECT will reduce the incidence of missed pathology.Conclusion: Patients with a normal NECT and no fever, meningism, confusion, focal/lateralizing signs, a history of tuberculosis or tumours, or risk factors for dural venous sinus thrombosis have a very small chance of missed pathology on NECT. The risk of contrast induced adverse events outweighs the risk of missing pathology on a normal NECT provided there is no clinical indication necessitating a CECT. Omitting unnecessary CECT will in turn reduce the risk of intravenous iodinated contrast and the radiation exposure to the patient. These two factors will ultimately reduce the running cost of the CT department and increase the throughput of patients. Alternatively omitting the NECT will reduce the radiation exposure to the patient.Reporting errors can be reduced by assessing and managing risk factors in each department i.e. viewing conditions and workload.

Neuromuscular paralysis caused by salivary proteins of ticks is a well-known complication after tick bites in Australia, North America, and South Africa. Symptoms may include general weakness, difficulty walking, ascending paralysis, and bulbar paralysis with diplopia, culminating in respiratory failure. In Europe, toxin-mediated paralysis has rarely been noted. We report a case of cranial nerve paralysis with delayed onset after a tick bite in northern Germany.

Thesis (Ph. D.)--Columbia University, 1899. / "This study was awarded the Cartwright Prize for 1899 by the Alumni Association of the College of Physicians and Surgeons, Columbia University, New York." "From Archives of neurology and psychopathology, volume II, 1899. Published simultaneously in the Archives of neurology and psychopathology and the Journal of comparative neurology, pages 21 to 319 and plates I to VII of volume II of the Archives being severally identical with pages 157 to 455 and plates XIV to XX of vol. IX of the Journal." Includes bibliographical references (p. 279-288).

Introdução: O schwannoma vestibular (SV) é um tumor benigno que se origina na bainha de schwann de um dos nervos vestibulares. De acordo com sua topografia lesões nos nervos cranianos facial, trigêmeo, coclear e bulbares podem estar presentes. Apesar do conhecimento da possibilidade de lesão nos nervos cranianos bulbares, a condução de estudos com o intuito de identificar alterações funcionais relacionadas raramente é estudada. Objetivos: Analisar fatores prognósticos de resultados funcionais relacionados aos nervos cranianos facial, trigêmeo, coclear e bulbares e correlacionar o prognóstico fonoaudiológico com os resultados de escalas funcionais finais dos nervos cranianos avaliados. Metodologia: Trata-se de um estudo de coorte com coleta de dados parcialmente retrospectiva que analisa a incidência de déficits funcionais de nervos cranianos em pacientes submetidos à exérese de SV, por meio de um protocolo de avaliação clínica estruturado (PAEC) especificamente para este estudo. O PAEC foi constituído de 2 sessões, sendo a primeira referente aos fatores prognósticos de sequelas e a segunda com dados funcionais referentes à deficiência auditiva (DA), comprometimento neurológico global (CNG), paralisia facial periférica (PFP), disfagia (DG) e fonação (DF). A coleta de dados foi realizada durante os meses de janeiro a junho do ano de 2016 no ambulatório de tumores da divisão de neurologia funcional do instituto de psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. A análise dos dados foi realizada por meio do software SPSS de modo inferencial univariado e multivariado adotando um p valor inferior a 0.05. Resultados: A amostra foi composta por 101 sujeitos, sendo 77,2% do sexo feminino e 22,8% do sexo masculino. A média de idade correspondeu à 47,1 anos. Foram identificados 20,8% pacientes portadores de neurofibromatose do tipo 2 (NTFII). A via de acesso cirúrgico preferencial foi a retrossigmoidea (92,1%) com média tumoral igual a 3,4cm.70% dos pacientes apresentaram ressecção total do tumor com uma única abordagem. Na análise univariada foram identificados os fatores preditivos de sequela por desfecho estatisticamente significantes tamanho tumoral, presença de neurofibromatose e ressecção total respectivamente- CNG ( < 0,001; 0,023; 0,010), DG (pvalor < 0,001; pvalor 0,007; pvalor < 0,001), DF (pvalor 0,013; pvalor 0,002), confirmados pela análise multivariada respectiva - CNG (Odds Ratio (OD) 1,5 - pvalor 0,07; OR 3,5 - pvalor 0,036; OR 2,4- pvalor 0,08), DG (OR 2,3 - pvalor 0,006; OR 5,7 - pvalor 0,015; OR 3,9 - pvalor 0,018) e DF (OR 1,6 -pvalor 0,062; OR 5,5 - pvalor 0,006). Para o desfecho PFP a análise univariada foi estatisticamente significante para NTFII (pvalor 0,009) e PFP prévia (pvalor < 0,001) confirmados pela análise multivariada (OR 24,6 - pvalor 0,009; OR 0,3 - pvalor < 0,001), neste desfecho foi realizado estudo correlacional entre as escalas funcionais de DG (pvalor < 0,001) e CNG (pvalor < 0,001) com resultados estatisticamente significantes para a correlação entre os desfechos. Os sinais clínicos da deglutição estatisticamente relevantes corresponderam em 44,4% fase preparatória oral e oral e 66,6% fase faríngea. Conclusões: Os fatores prognósticos significativos relacionados aos déficits funcionais encontrados neste trabalho foram o tamanho do tumor e presença de NFT II em todos os desfechos estudados. Para CNG e DG foi evidenciado ainda o fator preditor de tipo de ressecção estatisticamente significante. Os déficits funcionais de paralisia facial periférica se correlacionaram aos déficits da deglutição em fase oral e fase faríngea e de incapacidade funcional / Introduction: Vestibular schwannoma (VS) is a benign tumor that originates in the schwann sheath of one of the vestibular nerves. According to their topography lesions in the cranial, facial, trigeminal, cochlear and bulbar pairs may be present. Although knowledge of the possibility of injury in the lower cranial nerves, the conduction of studies with the purpose of identifying related functional alterations are rarely studied. Objectives: To analyze prognostic factors of functional results related to facial, trigeminal, cochlear and bulbary cranial nerves and to correlate the final functional prognosis of the cranial nerves with each other. Methodology: This is a cohort study with partial retrospective data collection that analyzes the incidence of functional deficits of cranial nerves in patients submitted to SV excision, using a structured clinical evaluation protocol (PAEC) specifically for this study . The PAEC consisted of 2 sessions, the first one referring to prognostic factors of sequelae and the second with functional data regarding hearing loss (DA), global neurological impairment (CNG), peripheral facial paralysis (PFP), dysphagia (DG) and Phonation (DF). The data collection was performed during the months of January to June of the year 2016 in the ambulatory of acoustic neurinoma of the Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo. Data analysis was performed using univariate and multivariate inferential mode SPSS software, adopting a value of less than 0.05. Results: The sample consisted of 101 subjects, being 77.2% female and 22.8% male. The mean age was 47.1 years. 20.8% of patients with neurofibromatosis type 2 (NTFII) were identified. The preferred surgical access route was retrossigmoid (92.1%) with a mean tumor equal to 3.4cm.70% of the patients presented total tumor resection with a single approach. In the univariate analysis, the predictive sequelae factors were identified by statistically significant tumor size, presence of neurofibromatosis and total resection, respectively - CNG ( < 0.001; 0.023; 0.010), DG (pvalor < 0.001, pvalor 0.007, pvalor < 0.001), DF (Odds ratio 0.05, pvalor 0.013, pvalor 0.002), confirmed by the respective multivariate analysis - CNG (Odds Ratio (OD) 1.5 - pvalor 0.07, OR 3.5 - pvalor 0.036, OR 2.4 - pvalor 0.08), DG (OR 2.3 - pvalor 0.006; OR 5.7 - Pvalor 0.015, OR 3.9 - pvalor 0.018) and DF (OR 1.6 -value 0.062, OR 5.5 - pvalor 0.006). For the PFP endpoint, the univariate analysis was statistically significant for NTFII (pvalor 0.009) and previous PFP (pvalor < 0.001) confirmed by the multivariate analysis (OR 24.6 - pvalor 0.009; OR 0.3 - pvalor < 0.001). The functional scales of DG (pvalor < 0.001) and CNG (pvalor < 0.001) with statistically significant results for the correlation between the outcomes. Significant clinical signs of swallowing corresponded in 44.4% oral and oral preparatory phase and 66.6% pharyngeal phase. Conclusions: The significant prognostic factors related to the functional deficits found in this study were tumor size, NFT II presence and resection type in all the outcomes studied. Functional deficits of peripheral facial paralysis were correlated with oral and pharyngeal deglutition deficits and functional disability

Background: Vagus nerve stimulation is increasingly applied to treat epilepsy, psychiatric conditions and potentially chronic heart failure. After implanting vagus nerve electrodes to the cervical vagus nerve, side effects such as voice alterations and dyspnea or missing therapeutic effects are observed at different frequencies. Cervical vagus nerve branching might partly be responsible for these effects. However, vagus nerve branching has not yet been described in the context of vagus nerve stimulation. Materials and methods: Branching of the cervical vagus nerve was investigated macroscopically in 35 body donors (66 cervical sides) in the carotid sheath. After X-ray imaging for determining the vertebral levels of cervical vagus nerve branching, samples were removed to confirm histologically the nerve and to calculate cervical vagus nerve diameters and cross-sections. Results: Cervical vagus nerve branching was observed in 29%of all cases (26% unilaterally, 3% bilaterally) and proven histologically in all cases. Right-sided branching (22%) was more common than left-sided branching (12%) and occurred on the level of the fourth and fifth vertebra on the left and on the level of the second to fifth vertebra on the right side. Vagus nerves without branching were significantly larger than vagus nerves with branches, concerning their diameters (4.79mm vs. 3.78mm) and cross-sections (7.24 mm2 vs. 5.28mm2). Discussion: Cervical vagus nerve branching is considerably more frequent than described previously. The side-dependent differences of vagus nerve branching may be linked to the asymmetric effects of the vagus nerve. Cervical vagus nerve branching should be taken into account when identifying main trunk of the vagus nerve for implanting electrodes to minimize potential side effects or lacking therapeutic benefits of vagus nerve stimulation.

Thesis (M.Sc. (Anatomy))--Mahidol University, 1982.

Introdução: O schwannoma vestibular (SV) é um tumor benigno que se origina na bainha de schwann de um dos nervos vestibulares. De acordo com sua topografia lesões nos nervos cranianos facial, trigêmeo, coclear e bulbares podem estar presentes. Apesar do conhecimento da possibilidade de lesão nos nervos cranianos bulbares, a condução de estudos com o intuito de identificar alterações funcionais relacionadas raramente é estudada. Objetivos: Analisar fatores prognósticos de resultados funcionais relacionados aos nervos cranianos facial, trigêmeo, coclear e bulbares e correlacionar o prognóstico fonoaudiológico com os resultados de escalas funcionais finais dos nervos cranianos avaliados. Metodologia: Trata-se de um estudo de coorte com coleta de dados parcialmente retrospectiva que analisa a incidência de déficits funcionais de nervos cranianos em pacientes submetidos à exérese de SV, por meio de um protocolo de avaliação clínica estruturado (PAEC) especificamente para este estudo. O PAEC foi constituído de 2 sessões, sendo a primeira referente aos fatores prognósticos de sequelas e a segunda com dados funcionais referentes à deficiência auditiva (DA), comprometimento neurológico global (CNG), paralisia facial periférica (PFP), disfagia (DG) e fonação (DF). A coleta de dados foi realizada durante os meses de janeiro a junho do ano de 2016 no ambulatório de tumores da divisão de neurologia funcional do instituto de psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. A análise dos dados foi realizada por meio do software SPSS de modo inferencial univariado e multivariado adotando um p valor inferior a 0.05. Resultados: A amostra foi composta por 101 sujeitos, sendo 77,2% do sexo feminino e 22,8% do sexo masculino. A média de idade correspondeu à 47,1 anos. Foram identificados 20,8% pacientes portadores de neurofibromatose do tipo 2 (NTFII). A via de acesso cirúrgico preferencial foi a retrossigmoidea (92,1%) com média tumoral igual a 3,4cm.70% dos pacientes apresentaram ressecção total do tumor com uma única abordagem. Na análise univariada foram identificados os fatores preditivos de sequela por desfecho estatisticamente significantes tamanho tumoral, presença de neurofibromatose e ressecção total respectivamente- CNG ( < 0,001; 0,023; 0,010), DG (pvalor < 0,001; pvalor 0,007; pvalor < 0,001), DF (pvalor 0,013; pvalor 0,002), confirmados pela análise multivariada respectiva - CNG (Odds Ratio (OD) 1,5 - pvalor 0,07; OR 3,5 - pvalor 0,036; OR 2,4- pvalor 0,08), DG (OR 2,3 - pvalor 0,006; OR 5,7 - pvalor 0,015; OR 3,9 - pvalor 0,018) e DF (OR 1,6 -pvalor 0,062; OR 5,5 - pvalor 0,006). Para o desfecho PFP a análise univariada foi estatisticamente significante para NTFII (pvalor 0,009) e PFP prévia (pvalor < 0,001) confirmados pela análise multivariada (OR 24,6 - pvalor 0,009; OR 0,3 - pvalor < 0,001), neste desfecho foi realizado estudo correlacional entre as escalas funcionais de DG (pvalor < 0,001) e CNG (pvalor < 0,001) com resultados estatisticamente significantes para a correlação entre os desfechos. Os sinais clínicos da deglutição estatisticamente relevantes corresponderam em 44,4% fase preparatória oral e oral e 66,6% fase faríngea. Conclusões: Os fatores prognósticos significativos relacionados aos déficits funcionais encontrados neste trabalho foram o tamanho do tumor e presença de NFT II em todos os desfechos estudados. Para CNG e DG foi evidenciado ainda o fator preditor de tipo de ressecção estatisticamente significante. Os déficits funcionais de paralisia facial periférica se correlacionaram aos déficits da deglutição em fase oral e fase faríngea e de incapacidade funcional / Introduction: Vestibular schwannoma (VS) is a benign tumor that originates in the schwann sheath of one of the vestibular nerves. According to their topography lesions in the cranial, facial, trigeminal, cochlear and bulbar pairs may be present. Although knowledge of the possibility of injury in the lower cranial nerves, the conduction of studies with the purpose of identifying related functional alterations are rarely studied. Objectives: To analyze prognostic factors of functional results related to facial, trigeminal, cochlear and bulbary cranial nerves and to correlate the final functional prognosis of the cranial nerves with each other. Methodology: This is a cohort study with partial retrospective data collection that analyzes the incidence of functional deficits of cranial nerves in patients submitted to SV excision, using a structured clinical evaluation protocol (PAEC) specifically for this study . The PAEC consisted of 2 sessions, the first one referring to prognostic factors of sequelae and the second with functional data regarding hearing loss (DA), global neurological impairment (CNG), peripheral facial paralysis (PFP), dysphagia (DG) and Phonation (DF). The data collection was performed during the months of January to June of the year 2016 in the ambulatory of acoustic neurinoma of the Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo. Data analysis was performed using univariate and multivariate inferential mode SPSS software, adopting a value of less than 0.05. Results: The sample consisted of 101 subjects, being 77.2% female and 22.8% male. The mean age was 47.1 years. 20.8% of patients with neurofibromatosis type 2 (NTFII) were identified. The preferred surgical access route was retrossigmoid (92.1%) with a mean tumor equal to 3.4cm.70% of the patients presented total tumor resection with a single approach. In the univariate analysis, the predictive sequelae factors were identified by statistically significant tumor size, presence of neurofibromatosis and total resection, respectively - CNG ( < 0.001; 0.023; 0.010), DG (pvalor < 0.001, pvalor 0.007, pvalor < 0.001), DF (Odds ratio 0.05, pvalor 0.013, pvalor 0.002), confirmed by the respective multivariate analysis - CNG (Odds Ratio (OD) 1.5 - pvalor 0.07, OR 3.5 - pvalor 0.036, OR 2.4 - pvalor 0.08), DG (OR 2.3 - pvalor 0.006; OR 5.7 - Pvalor 0.015, OR 3.9 - pvalor 0.018) and DF (OR 1.6 -value 0.062, OR 5.5 - pvalor 0.006). For the PFP endpoint, the univariate analysis was statistically significant for NTFII (pvalor 0.009) and previous PFP (pvalor < 0.001) confirmed by the multivariate analysis (OR 24.6 - pvalor 0.009; OR 0.3 - pvalor < 0.001). The functional scales of DG (pvalor < 0.001) and CNG (pvalor < 0.001) with statistically significant results for the correlation between the outcomes. Significant clinical signs of swallowing corresponded in 44.4% oral and oral preparatory phase and 66.6% pharyngeal phase. Conclusions: The significant prognostic factors related to the functional deficits found in this study were tumor size, NFT II presence and resection type in all the outcomes studied. Functional deficits of peripheral facial paralysis were correlated with oral and pharyngeal deglutition deficits and functional disability

No description available.

Os macacos Cebus apella são hábeis com suas mãos e capazes de utilizar ferrementas (paus e pedras) para resolver problemas, podendo ser treinados como assistentes de pessoas quadriplégicas. São escassas ainda as informações em neuroanatomia desses primatas, o que motiva a presente pesquisa, cujo propósito é o de enfocar a morfologia externa e interna do tronco encefálico. Foram estudados 20 espécimes do macaco Cebus apella que já estavam fixados com formol a 10%, pertencentes ao acervo de pesquisa do laboratório de Anatomia da Universidade Federal de Uberlândia. Após isolamento do encéfalo e remoção das meninges procedeu ? se ao estudo da superfície externa em 14 peças. A dissecção por técnica usual preservou características morfológicas da superfície e origem aparente de nervos cranianos, que foram identificados. Em análise macroscópica, o tronco encefálico mostra ? se bem desenvolvido destacando ? se ainda em sua face lateral a origem aparente do nervo trigêmeo e os pedúnculos cerebelares médios, bem evidentes. Na face dorsal, em relação ao IV ventrículo identificam ? se os véus medulares superior e inferior, bem como o sulco mediano e a eminência medial. Os pedúnculos cerebelares superior e inferior também são bem destacados. Na medula oblonga são identificados, entre outros, os relevos correspondentes às olivas e às pirâmides, além da fissura mediana anterior e a região da decussação das pirâmides, Nem sempre são nítidos o sulco bulbo ? pontino e o forame cego. Os fascículos grácil e cuneiforme são bastante desenvolvidos bem como os tubérculos correspondentes. Para os estudos das estruturas internas do tronco encefálico, 6 peças, já fixadas, foram congeladas com nitrogênio líquido e cortadas no criostato entre ?27&ordm; C e ? 30&ordm; C, seguindo ? se a feitura de cortes transversais, em seis níveis (colículos superior e inferior, origem aparente do nervo trigêmeo, porções superior, média e inferior da oliva, e decussação das pirâmides), com espessura de 60 &micro;c, corados segundo o método de Mulligan. As estruturas evidenciáveis são descritas com detalhes comparando ? se os dados obtidos com os da literatura consultada. Os termos anatômicos foram referidos segundo a Terminologia Anatômica Internacional, 1&ordf; edição brasileira ? 2001, Ed. Manole Ltda. / The Cebus apella monkey are able to use their nands and to use tools like woods and stones to solve problems. They can be trained to act as quadriplégicas people?s assistants. The Neuroanatomy information about these primates are little, that?s the reason for this research and its purpose is to accomplish a macroscophial anatomic study of encephalic trunk external and internal surface structure. It was studied Cebus apella monkeu 20 especimens that was already fixed on 10% formaldehyde. These monkeys are from research?s heap of Universidade Federal de Uberlândia. The monkey encephalon were removed using an osteótomo. After removing the meninges, theirs external surface study was started on 14 of them. The dissection using usual technique could preserve the morphological characteristics of the surface and cranial nerve apparent origim, that could be identified too. Under a macroscophical analysis, the encephalic trun looks very elaborated and the trigemini nerve and pedunculus cerebellaris aparent origin, very evident, was stood out in its lateral face. In the dorsal face, in relation to fourth ventricle, the inferior and superior velum medullare could be identified as well as the sulcus medianus and the eminentia medialis. The superior pedunculus cerebellaris, as well as the inferior ones, were very stood out too. On the medulla oblongata were identified, beyond others, the relieves corresponding to the oliva and the decussatio pyramidum region. The sulcus bulbus ? pons and the foramen caecum not always are bright. The fasciculus gracilis, as well as the cuneatus ones, are very elaborated as well as the corresponding tuberculuns.The brain stem internal structure study 6 already fixed pieces were froze with liquid nitrong and cut in criostato, under the temperature between ?27&ordm;C and ? 30&ordm; C. After this, transversal cuts were made on 6 levels (superior and inferior nerve trigemini aparent origin, olivas superior, medium and inferior portion and decussatio pyramidum), with the thickness of 60&micro;c, roddy according to the Mulligan method. The evidentiable structures are described in details comparing data obtained from the consulted literature. The anatomic terms were aforesaid according to Terminologia Anatômica Internacional, 1&ordf; edição brasileira ? 2001, Ed. Manole Ltda.