A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Summary: The human HOXA1 mutation syndromes commonly present with abnormalities of the inner ear and internal carotid arteries. Previous cases describe varying degrees of hypoplasia or aplasia of the affected structures, often with asymmetrical involvement. We present imaging findings documenting complete absence of the internal carotid arteries bilaterally with bilateral Michel aplasia of the inner ear, which, to our knowledge, has not been previously reported. Based on the number of cases identified and birth rates within studied populations, we estimated the incidence of ABDS at 0.5-1:1000 live births on the White River Apache Reservation and 1:3000 live births in the Navajo population. If accurate, this suggests a carrier frequency similar to that for cystic fibrosis in Caucasian populations. ABDS may represent a significantly underrecognized disorder among Athabaskan Native Americans, raising questions of the possible benefit of genetic counseling for affected families. However, cultural considerations in this population bring into question the possible conflict between counseling based on gene theory and traditional beliefs.

名古屋大学博士学位論文 学位の種類 : 博士(医学)(課程) 学位授与年月日:平成21年3月25日 靍見有史氏の博士論文として提出された

Submitted by JOÃO AUGUSTO LEONEL DE SOUZA null (desouza.ja@gmail.com) on 2016-09-09T16:38:02Z No. of bitstreams: 1 Dissertação final.pdf: 1556586 bytes, checksum: e53dadd03ff83fdae3ae4b4e49d912ac (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-09-13T13:15:00Z (GMT) No. of bitstreams: 1 souza_jal_me_jabo.pdf: 1556586 bytes, checksum: e53dadd03ff83fdae3ae4b4e49d912ac (MD5) / Made available in DSpace on 2016-09-13T13:15:00Z (GMT). No. of bitstreams: 1 souza_jal_me_jabo.pdf: 1556586 bytes, checksum: e53dadd03ff83fdae3ae4b4e49d912ac (MD5) Previous issue date: 2016-05-30 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A mielografia é muito realizada na prática veterinária, entretanto, existem importantes efeitos adversos associados a ela. O objetivo da presente pesquisa foi avaliar os possíveis efeitos sobre a pressão subaracnoide, parâmetros cardiorrespiratórios (TC, FR, FC, PAS, PAD, PAM, EtCO2, SpO2, InspISO e FeISO) e do índice de pressão-volume (PVI) em ovelhas hígidas submetidas à mielografia lombar. Foram utilizados 8 ovinos fêmeas sadios, os quais foram pré-medicados com Midazolan (0,5 mg/Kg), indução anestésica com Propofol (3-6 mg/Kg) e manutenção anestésica com Isoflurano. Primeiramente, os animais foram submetidos à punção da cisterna magna para monitoramento da pressão subaracnoide (Sap). Ato contínuo, foi realizado a mielografia lombar por meio da aplicação de Iohexol (300 mg/mL, taxa de 4,1 mL/min e dose de 0,4 mL/Kg). Os momentos estudados foram: imediatamente após a estabilização anestésica (M0), durante a punção lombar (M1), dois, quatro e seis minutos após a aplicação do contraste (M2, M3 e M4, respectivamente). A Sap foi colhida imediatamente após à punção atlanto-occipital (Sap0), o maior valor durante a aplicação do meio de contraste (Sapmax), dois, quatro e seis minutos após a aplicação do meio de contraste (Sap2, Sap3 e Sap4, respectivamente). Constataram-se diferenças significativas a 5% de confiança entre os momentos as variáveis: TC, PAS, PAD, PAM, InspISO, FeISO Sap e PPC pelo teste de Tukey. Com a correlação de Pearson TC/FR, FC/SpO2, FC/FR, FR/PAS, FR/PAD, FR/PAM, FR/PPC, Sap/PAS, PAD/Sap, PAM/Sap, EtCO2/SPO2, EtCO2/InsplSO, PAD/PAS, PAS/PAM, PAM/PAD, FelSO/InsplSO e Sap/PPC. Com base nos resultados concluímos que os valores de PVI, para a espécie ovina, com a metodologia empregada foi de 17,91 mL. Durante a realização da mielografia lombar ocorre aumento significativo da Sap (média de 101,87 mmHg), provocando grave redução da PPC. / The myelography is very accomplished in veterinary practice, however there are significant adverse effects associated with it. The aim of this research was to evaluate the possible effects of subarachnoid pressure, cardiorespiratory parameters (TC, FR, FC, PAS, PAD, PAM, EtCO2, SpO2, InspISO and FeISO) and pressure-volume index (PVI) in sheep otherwise healthy undergoing lumbar myelography. 8 healthy female sheep were used, which were pre-medicated with midazolam (0.5 mg / kg) anesthetic induction with propofol (3-6 mg / kg) and anesthesia maintained with isoflurane. First, the animals were submitted to the puncture of the cisterna magna and pressure monitoring. Subsequently, the lumbar myelography was performed by application of iohexol (300 mg / ml at rate 4.1 ml / min and a dose of 0.4 ml / kg). The time points studied were: immediately after anesthetic stabilization (M0) during a lumbar puncture (M1), two, four and six minutes after application of contrast (M2, M3 and M4, respectively). Subarachnoid pressure (Sap) was taken immediately after the atlanto-occipital punch (Sap0), the largest value during application of the contrast medium (Sapmax), two, four and six minutes after application of the contrast medium (SAP2, Sap3 and Sap4, respectively). They found significant differences at 5% confidence between times the variables TC, PAS, PAD, PAM, InspISO, FeISO Sap and PPC by Tukey test. With the Pearson correlation TC/FR, FC/SpO2, FC/FR, FR/PAS, FR/PAD, FR/PAM, FR/PPC, Sap/PAS, PAD/Sap, PAM/Sap, EtCO2/SPO2, EtCO2/InsplSO, PAD/PAS, PAS/PAM, PAM/PAD, FelSO/InsplSO and Sap/PPC Based on the results we conclude that the PVI values for the sheep, the methodology employed was 17.91 mL, close to normal values for adults of the human species. While performing the lumbar myelography is significant increase in Sap (average of 101.87 mmHg), causing severe reduction in PPC.

This cross-sectional study examined neurobiologic correlates of depression in ischemic stroke patients. Depression severity was measured with a standardized scale (Center for Epidemiologic Studies Depression Scale; CES-D). Eighty-two patients (53.1% male, mean (± SD) age 71.9 ± 14.2 years, mean (± SD) National Institutes of Health Stroke Scale (NIHSS) score 4.6±4.7, mean (± SD) CES-D score 12.6 ± 10.8) were recruited. A linear regression controlling for age and stroke severity (NIHSS) determined that the kynurenine to tryptophan ratio (β= -0.105, p=0.369) was not significantly associated with CES-D (primary hypothesis) (overall model R2=0.069, F3,73=1.805, p=0.154). Secondary analyses suggested one instance of cytokines favouring inflammatory states in mild depressive symptomatology; IFN-Ɣ/IL-10 (OR, 2.17; 95% CI, 1.02-4.64, p=0.045). For the most part however, inclusion of cytokines and neuroimaging correlates such as atrophy, lesion location and white matter changes were non-significant. Longitudinal studies are necessary to identify the possible neurobiologic correlates of depressive symptoms post-stroke.

This cross-sectional study examined neurobiologic correlates of depression in ischemic stroke patients. Depression severity was measured with a standardized scale (Center for Epidemiologic Studies Depression Scale; CES-D). Eighty-two patients (53.1% male, mean (± SD) age 71.9 ± 14.2 years, mean (± SD) National Institutes of Health Stroke Scale (NIHSS) score 4.6±4.7, mean (± SD) CES-D score 12.6 ± 10.8) were recruited. A linear regression controlling for age and stroke severity (NIHSS) determined that the kynurenine to tryptophan ratio (β= -0.105, p=0.369) was not significantly associated with CES-D (primary hypothesis) (overall model R2=0.069, F3,73=1.805, p=0.154). Secondary analyses suggested one instance of cytokines favouring inflammatory states in mild depressive symptomatology; IFN-Ɣ/IL-10 (OR, 2.17; 95% CI, 1.02-4.64, p=0.045). For the most part however, inclusion of cytokines and neuroimaging correlates such as atrophy, lesion location and white matter changes were non-significant. Longitudinal studies are necessary to identify the possible neurobiologic correlates of depressive symptoms post-stroke.

A worldwide demographic shift is currently occurring, with rapidly increasing numbers of elderly individuals. Since the incidence of neurodegenerative disease generally increases with age, this entails an increase in dementia prevalence. There are several strong incentives for establishing robust and widely available imaging methods for the early diagnosis of these diseases. Atrophy patterns are evident only late in the disease process, and the distinction from healthy ageing can often be elusive. For early diagnosis, physiologic parameters such as perfusion or metabolism must be assessed. The available modalities all have restricted clinical usefulness. The main aim of this thesis was to advance the clinical usefulness of perfusion and metabolism imaging in patients with neurodegenerative dementia, with a focus on visual assessment. A cohort of patients with neurodegenerative dementia was included, along with an age-matched control group. All subjects underwent MRI, including a pseudocontinuous ASL sequence and FDG-PET. In papers II and III, a subgroup containing both patients and controls underwent a second FDG-PET with reduced dose. In paper IV, the material was combined with a similar cohort from Amsterdam. Paper I showed that spatial smoothing increased the correlation between visually assessed perfusion and metabolism levels as displayed with FDG-PET. However, the distinction between patients and healthy controls was less satisfactory due to false positives. Paper II showed that differences in regional standard uptake value ratios between normal- and low-dose FDG-PET were small and without clinically significant bias. Paper III showed that the diagnostic performance of Z-score maps showing regions of significant deficits in metabolism was highly similar in normal- and low-dose FDG-PET images.  Paper IV showed that ASL perfusion-based Z-score maps can be used for diagnostic purposes with high specificity, but inferior sensitivity, compared to FDG-PET. In conclusion, the included studies address aspects of the visual assessment of perfusion and metabolism neuroimaging, with a focus on clinical usefulness in diagnosing neurodegenerative dementia.

La neuroradiologie Interventionnelle est devenue une spécialité médicale à part entière en évolution permanente avec l'amélioration des technologies radiologiques et endovasculaires. Néanmoins, de trop nombreuses complications liées à la technique elle-même sont encore rapportées. Basés sur notre expérience clinico-radiologique, nous nous sommes plus particulièrement intéressés aux complications thromboemboliques grâce à de nouvelles technologies biologiques permettant d'envisager une analyse des lésions vasculaires à l'échelle cellulaire (Cellsearch®). Ainsi au cours de différents examens diagnostiques et thérapeutiques nous avons analysé les taux artériels et veineux de cellules endothéliales circulantes à différents temps de la procédure. Nous avons démontré l'agression du matériel endovasculaire sur les parois artérielles induisant un relargage immédiat de CECs unitaires et en amas de taille variable, parfois géants (300 µm). Les amas présentant une taille supérieure aux diamètres des microcapillaires ne peuvent pas migrer dans le compartiment veineux et sont donc potentiellement à l'origine d'une occlusion artérielle très distale responsable de lésions microischémiques qualifiées de silencieuses car asymptomatique dans l'ensemble des cas observés. Les lésions pariétales artérielles induites sont ensuite probablement réparées par un mécanisme dynamique mettant en jeu une augmentation lente et progressive des CEPs jusqu'à l'obtention d'une réparation de l'endothélium. Au delà des facteurs mécaniques endovasculaires, l'analyse cellulaire de cette cinétique destruction-régénération des parois artérielles pourrait s'avérer intéressante dans l'évaluation de l'endothélialisation des endoprothèses intracrâniennes. / Permanents Improvements in radiological and endovascular devices made the Interventional Neuroradiology considered as a complete medical specialty. However, too many procedural complications due to the devices remain observed in all reported series. On the basis of our clinical center experience we decided to analyze thromboembolic complications by using new biological tests allowing to the detection of circulating endothelial cells. During cerebral diagnostic or therapeutic angiography, arterial and venous CECs rates were analyzed before, during, and after endovascular procedures. Thus, we demonstrated the potential arterial wall injury following catheterization that induced unit and cluster of CECs, some of them were giants (300 µm). Clusters presenting with a size up than those described from microcapillary lumen cannot go through venous compartment, and potentially block into a distal artery inducing microischemic stroke (silent embolism) as observed in this work. In addition, the induced arterial wall injury is probably regenerated by a dynamic mechanism involving a delayed increase of CEPs rates, until the new endothelialization. Over endovascular mechanism factor analysis, the CECs-CEPs investigations could be an interesting strategy in the monitoring of intracranial endoprothesis endothelialization.

No description available.

INTRODUÇÃO: A angioplastia carotídea com stent (ACS) sob proteção cerebral é opção terapêutica em pacientes com estenose carotídea. Existe o risco de embolia apesar da utilização do filtro e as modificações na perfusão cerebral após tratamento da estenose carotídea não são claras. O propósito deste estudo é avaliar, após ACS sob proteção cerebral por filtros, modificações nas seqüências de RM de difusão (DWI) e perfusão (PWI), correlacionando-as com os aspectos técnicos da ACS, com as características da estenose e com dados demográficos dos pacientes. MÉTODO: Trinta e seis pacientes portadores de estenose carotídea com idade média de 72,08 anos foram submetidos a exame de RM um dia antes e até 72 horas após a ACS com filtro de proteção. Todos os pacientes eram assintomáticos após a ACS. Áreas de restrição na DWI após a ACS foram correlacionadas com aspectos demográficos, com aspectos da técnica de angioplastia e com a presença de infartos prévios por RM. Os parâmetros CBV volume sanguíneo cerebral, MTT tempo de trânsito médio e TTP tempo para o pico são empregados para análise por PWI. RESULTADOS: Na DWI, 18 de 36 (50,00%) pacientes apresentaram novos focos (NF) de restrição na DWI após ACS. Todos os NF foram clinicamente silenciosos (100%). Estes NF eram localizados em território cerebral nutrido pela artéria carótida submetida à ACS em 77,19% e menores que 10 mm em 91,53%. Os NF em território cerebral não irrigado pela artéria carótida submetida à angioplastia correspondiam a 22,81% destes. A presença de infartos cerebrais prévios na RM foi o único fator com influência no aparecimento de NF (p=0,037). Fatores demográficos e aspectos relacionados com a técnica de angioplastia não tiveram importância na gênese dos NF. Na PWI foi observada melhora nos parâmetros temporais TTP (p<0,001) e MTT (p=0,019) quando comparados de forma normalizada em relação ao território contralateral. CONCLUSÃO: Os novos focos de restrição na DWI após ACS (NF) foram mais comuns no território ipsilateral (77,19%), no entanto houve NF no território contralateral à ACS (22,81%), possivelmente, associados ao cateterismo diagnóstico. Os NF, na sua maioria, são de pequeno diâmetro (<10 mm em 91,53%). Melhora precoce na PWI, observada nos dados normalizados, foi demonstrada nos parâmetros temporais (TTP e MTT). / INTRODUCTION: Carotid angioplasty with stent (CAS) under cerebral protection is a therapeutic option in patients with carotid stenosis. There is a risk of embolism even with a filter, and changes in cerebral perfusion after treatment are not clearly understood. The purpose of this study was to evaluate changes in diffusion- (DWI) and perfusion- (PWI) weighted magnetic resonance imaging (MRI) sequences correlating them with the technical aspects of CAS, stenosis characteristics and patient demographic data. METHODS: Thirty-six carotid stenosis patients with an mean age of 72.08 years were submitted to MRI exam one day before and up to 72 hours after CAS with filter protection. All patients were asymptomatic after CAS. Areas of restriction on DWI were correlated to demographic aspects, technique of angioplasty as well the presence of previous stroke by MRI. The parameters, CBV - cerebral blood volume; MTT - mean transit time, and TTP- time to peak, are used for PWI analysis. RESULTS: Eighteen of the 36 patients (50.00%) presented new focus (NF) of restriction by DWI after CAS. All new focus were clinically silent. The NF were located in the cerebral area fed by the carotid artery submitted to CAS in 77.19% and smaller than 10mm in 91.53%. NF in cerebral area not irrigated by carotid artery submitted by angioplasty correspond to 22,81 %. The presence of previous ischemic lesion on MRI was the only factor which influenced the appearance of NF (p=0.037). Demographic factors and aspects related to angioplasty technique had no importance on NF genesis. Improvement in PWI timing parameters - TTP (p<0.001) and MTT (p=0.019) were observed in relation to the contralateral territory (normalized data). CONCLUSION: The restriction NF in the DWI after CAS are more common in the ipsilateral territory (77.19%), however there were some NF in the contralateral territory to the CAS (22.81%), possibly associated with diagnostic catheterization. Most of the NF were small in diameter (<10mm in 91.53%). Short-term improvement in PWI were demonstrated by normalized timing parameters (TTP and MTT).

INTRODUÇÃO: A angioplastia carotídea com stent (ACS) sob proteção cerebral é opção terapêutica em pacientes com estenose carotídea. Existe o risco de embolia apesar da utilização do filtro e as modificações na perfusão cerebral após tratamento da estenose carotídea não são claras. O propósito deste estudo é avaliar, após ACS sob proteção cerebral por filtros, modificações nas seqüências de RM de difusão (DWI) e perfusão (PWI), correlacionando-as com os aspectos técnicos da ACS, com as características da estenose e com dados demográficos dos pacientes. MÉTODO: Trinta e seis pacientes portadores de estenose carotídea com idade média de 72,08 anos foram submetidos a exame de RM um dia antes e até 72 horas após a ACS com filtro de proteção. Todos os pacientes eram assintomáticos após a ACS. Áreas de restrição na DWI após a ACS foram correlacionadas com aspectos demográficos, com aspectos da técnica de angioplastia e com a presença de infartos prévios por RM. Os parâmetros CBV volume sanguíneo cerebral, MTT tempo de trânsito médio e TTP tempo para o pico são empregados para análise por PWI. RESULTADOS: Na DWI, 18 de 36 (50,00%) pacientes apresentaram novos focos (NF) de restrição na DWI após ACS. Todos os NF foram clinicamente silenciosos (100%). Estes NF eram localizados em território cerebral nutrido pela artéria carótida submetida à ACS em 77,19% e menores que 10 mm em 91,53%. Os NF em território cerebral não irrigado pela artéria carótida submetida à angioplastia correspondiam a 22,81% destes. A presença de infartos cerebrais prévios na RM foi o único fator com influência no aparecimento de NF (p=0,037). Fatores demográficos e aspectos relacionados com a técnica de angioplastia não tiveram importância na gênese dos NF. Na PWI foi observada melhora nos parâmetros temporais TTP (p<0,001) e MTT (p=0,019) quando comparados de forma normalizada em relação ao território contralateral. CONCLUSÃO: Os novos focos de restrição na DWI após ACS (NF) foram mais comuns no território ipsilateral (77,19%), no entanto houve NF no território contralateral à ACS (22,81%), possivelmente, associados ao cateterismo diagnóstico. Os NF, na sua maioria, são de pequeno diâmetro (<10 mm em 91,53%). Melhora precoce na PWI, observada nos dados normalizados, foi demonstrada nos parâmetros temporais (TTP e MTT). / INTRODUCTION: Carotid angioplasty with stent (CAS) under cerebral protection is a therapeutic option in patients with carotid stenosis. There is a risk of embolism even with a filter, and changes in cerebral perfusion after treatment are not clearly understood. The purpose of this study was to evaluate changes in diffusion- (DWI) and perfusion- (PWI) weighted magnetic resonance imaging (MRI) sequences correlating them with the technical aspects of CAS, stenosis characteristics and patient demographic data. METHODS: Thirty-six carotid stenosis patients with an mean age of 72.08 years were submitted to MRI exam one day before and up to 72 hours after CAS with filter protection. All patients were asymptomatic after CAS. Areas of restriction on DWI were correlated to demographic aspects, technique of angioplasty as well the presence of previous stroke by MRI. The parameters, CBV - cerebral blood volume; MTT - mean transit time, and TTP- time to peak, are used for PWI analysis. RESULTS: Eighteen of the 36 patients (50.00%) presented new focus (NF) of restriction by DWI after CAS. All new focus were clinically silent. The NF were located in the cerebral area fed by the carotid artery submitted to CAS in 77.19% and smaller than 10mm in 91.53%. NF in cerebral area not irrigated by carotid artery submitted by angioplasty correspond to 22,81 %. The presence of previous ischemic lesion on MRI was the only factor which influenced the appearance of NF (p=0.037). Demographic factors and aspects related to angioplasty technique had no importance on NF genesis. Improvement in PWI timing parameters - TTP (p<0.001) and MTT (p=0.019) were observed in relation to the contralateral territory (normalized data). CONCLUSION: The restriction NF in the DWI after CAS are more common in the ipsilateral territory (77.19%), however there were some NF in the contralateral territory to the CAS (22.81%), possibly associated with diagnostic catheterization. Most of the NF were small in diameter (<10mm in 91.53%). Short-term improvement in PWI were demonstrated by normalized timing parameters (TTP and MTT).