Thesis (MMed)--University of Stellenbosch, 2004. / ENGLISH ABSTRACT: Numerous tests exist for the assessment of general cognitive functioning. Most of these tests were developed within the discipline of psychology. Neuropsychological tests are very useful, but have some limitations. Administration of the tests is limited to a psychologist, is very timeconsuming in that it can take 3-8 hours to administer and often need specialized equipment. At the other end of the continuum are very brief screening tests. General practitioners, psychiatrists and occupational therapists, in addition to psychologists, also use these tests. Although useful, the short tests only provide limited information. An intermediate level test streamlining the assessment process between the very short and longer neuropsychological tests is therefore introduced by this study. The Bedside Cognitive Assessment Battery (BCAB) was developed in 1995 and are since used, at Tygerberg Hospital's Memory Clinic, to assess patients and teach students. The test comprehensively assesses the six main classes of cognitive functioning, namely attention and concentration, speech, memory, motor functioning, perceptual functioning and executive functioning. Approximately 35-45 minutes is required for administration and training is needed to administer the BCAB. No specialized equipment is needed for administration. The battery can therefore be used at the bedside, in the office or at old age homes. The aims of this study were to validate the BCAB for use with people aged eighteen years and older, and provide normative values for use in clinical settings. The test was revised in 1997 and 2001, and extensively so in 2002, but was never formally evaluated for validity. Well-known single tests were used to compile the BCAB. Most of these tests have proven validity and reliability, but only for foreign populations. In addition, some items were reformulated and others created by the researchers. The introduction of normative values would also be useful to assist in the delineation of cognitively intact and impaired individuals. This study succeeded in providing a table of normative values. One-hundred-and-sixty Afrikaans and English participants, and fourteen Xhosa participants were assessed in their mother tongue language. This project thus also introduced a Xhosa version of the BCAB. The purpose of the Xhosa version was to address the lack of culturally relevant cognitive assessment instruments. Results were evaluated for the effects of the variables' language, gender, age and education. The effect of language was most noticeable in the Xhosa group. Gender did not affect results as dramatically as age and especially, education. These significant effects on the aforementioned variables have been described in previous reports. The BCAB is thus relevant and useful as a detector of mild to moderate impairment. It can also be used to identify specific impairment. This can narrow down the investigation of psychologists, thus saving time and money. In addition, medical and nonmedical staff can use the BCAB. Some limitations were also identified. The sample used may limit the generalization of results. Some test items also need revision, along with further validation studies. Clinicians are therefore advised to use the BCAB only in addition to complete clinical examinations when making decisions regarding a patient's cognitive status. The BCAB appears to be a valid tool for bedside assessment. However, this study could only set the stage for further research, especially studies concerned with establishing normative values. / AFRIKAANSE OPSOMMING: Verskeie toetse bestaan vir die evaluering van algemene kognitiewe funksionering, waarvan die meeste ontwikkel is binne die sielkunde. Neuro-sielkundige toetse is baie bruikbaar, maar het sekere beperkings. Administrasie van die toetse is beperk tot sielkundiges, maar tydrowend weens 'n tydsduur van drie tot agt uur, en verg dikwels gespesialiseerde toerusting. Aan die ander kant is heelwat kart siftings-toetse beskikbaar. Aigemene praktisyns, sielkundiges en arbeidsterapeute, asook sielkundiges, gebruik dit. Hoewel bruikbaar, bied die kart toetse beperkte inligting. 'n lntermediere vlak toets om die evaluerings-proses tussen kart en langer neuro-sielkundige toetse te integreer word met hierdie studie beoog. Die Bedkant Kognitiewe Evaluasie Battery (BKEB) is in 1995 ontwikkel en gebruik in die Geheue-kliniek van die Tygerberg Hospitaal om pasiente te evalueer en studente op te lei. Die toets is gerig op die omvattende evaluering van die ses hoof-klasse van kognitiewe funksionering. Hierdie klasse omvat aandag en konsentrasie, spraak, geheue, motoriese funksionering, perseptuele funksionering en uitvoerende funksionering. Sowat 35 tot 45 minute word benodig vir administrasie terwyl opleiding vereis word vir die neem van die toets. Geen gespesialiseerde toerusting is nodig nie. Die battery kan dus by die bedkant, in die kantoor of in ouetehuise gebruik word. Die doelwitte van hierdie studie is om die BKEB te evalueer in gebruik by 18-jariges en ouer, en normatiewe waardes te bepaal vir gebruik in kliniese omgewings. Die toets is in 1997 en 2001 hersien. In 2002 is dit uitvoerig hersien, maar nooit ge-evalueer vir geldigheid nie. Bekende enkel-toetse is gebruik am die BKEB saam te stel. Dit is as geldig en betroubaar bewys, hoewel slegs onder buitelandse bevolkingsgroepe. Hierbenewens is sekere items herformuleer en ander bygewerk deur die navorsers. Normatiewe waardes sal oak handig wees in die afbakening van kognitief normaal-funksionerende en kognitief-ingekorte individue. Hierdie studie het daarin geslaag am 'n tabel van normatiewe waardes daar te stel. Een-honderd-en-sestig Afrikaans- en Engels-sprekendes, en 14 Xhosa-sprekendes is tydens hierdie studie in hulle moedertaal ge-evalueer. Hierdie projek het dus oak 'n Xhosaweergawe van die BKEB geskep. Die doel van die Xhosa-weergawe was am die gebrek aan 'n kultureel toepaslike kognitiewe instrument te beklemtoon. Resultate is ge-evalueer gedagtig aan veranderlikes soos taal, geslag, ouderdom en opleidingsvlak. Taal het die grootste invloed gehad op uitslae van Xhosa-deelnemers. Geslag het nie die uitslae so dramaties bernvloed soos ouderdom, en veral opleidingsvlak nie. Literatuur het meestal die groot uitwerking van hierdie veranderlikes bevestig. Die BKEB is dus relevant en handig in die naspeuring van ligte tot matige kognitiewe ingekortheid. Dit kan ook gebruik word om spesifieke kognitiewe ingekortheid te identifiseer. Die kan die omvang van ondersoek deur sielkundiges vernou, wat kan lei tot In groot besparing in tyd en geld. Hierbenewens kan mediese en nie-mediese personeel aangewend word in die gebruik van die BKEB. Sekere tekortkominge is ge·,dentifiseer. Die steekproef mag egter die veralgemening van die uitslae beperk. Sekere toets-items mag ook hersiening vereis, tesame met verdere geldigheid-studies. Kliniese praktisyns word daarom aangeraai om die BKEB slegs in aanvulling tot omvattende kliniese ondersoeke te gebruik vir besluite m.b.t. In pasient se kognitiewe status. Die BKEB kom voor as In geldige instrument vir bedkant evaluering. Hierdie studie kon egter slegs die tafel dek vir verdere ondersoek, veral t.o.v. studies wat poog om normatiewe waardes daar te stel.

INTRODUCTION: HIV/AIDS is a global health problem, with Sub-Saharan Africa the most affected. “Neuro-AIDS” refers to the extensive neuropathological manifestations of the disease. Neuroimaging of the HIV-infected individual plays a fundamental role in their work-up. Limited resources, however, drive the development of imaging protocols based on clinical signs. ‘Confusion’ may or may not represent a significant presenting sign and needs to be investigated, as it is the basis of referral of a significant number of patients for CT scanning. AIM: To determine the frequency of positive findings of head CT in HIV-infected adults presenting with confusion with/without associated neurology, and correlate them with the degree of immunosuppression, presence of CSF abnormality and their ARV therapy status. METHOD: CT brain scans of adult patients, who were HIV-positive and presented with confusion in Johannesburg, Gauteng, were retrospectively reviewed. The neurological status, CD4 counts, LP results and their ARV therapy status were documented. RESULTS: 30% of our HIV-infected patients presented with confusion. There were 156 patients who were included. CT scans were abnormal in 81%. We found that ‘associated neurology’ was a weak predictor for abnormal CT, making it a poor screening tool. A positive LP was predictive of infection (p=0.04 for focal infection, p=0.03 for infected surface collection) and infarction (p<0.01) on CT. CD4 count, LP results and ARV therapy were found to be abnormal in the majority of patients. CONCLUSIONS: CT was abnormal in the majority of HIV-infected patients presenting with confusion. Neurology was an unreliable clinical indicator. A positive LP was a good predictor for CT evidence of infection and infarction. The clinical parameters such as CD4 counts, LP results and ARV therapy, were abnormal in the majority of patients. If any of these parameters are abnormal in a patient with a normal CT, we believe this should motivate for further imaging with MRI.

No description available.

No description available.

Introdução: A Neuropatia auditiva/Dessincronia auditiva (NA) é um transtorno que foi identificado há apenas 20 anos, os pacientes que possuíam este transtorno eram diagnosticados como deficientes auditivos como conseqüência da falha no diagnóstico. Com o surgimento do registro das Emissões Otoacústicas e sua presença no repertório de testes de avaliação auditiva, foi possível ao clínico fazer o diagnóstico de NA. Assim sendo, é possível que alguns indivíduos que foram diagnosticados como portadores de uma perda auditiva neurossensorial, tivessem, na verdade, NA. Objetivos: O objetivo deste estudo foi caracterizar o tipo e grau da deficiência auditiva em uma população de deficientes auditivos da cidade de São Paulo; verificar a época da suspeita pelos pais da deficiência auditiva bem como do diagnóstico audiológico nestes indivíduos; identificar os participantes cujas avaliações comportamentais são incompatíveis com as avaliações eletrofisiológicas, visando identificar casos de Neuropatia Auditiva e realizar estudo qualitativo de casos dos participantes com incompatibilidade de respostas nas avaliações comportamentais e eletrofisiológicas. Método: Foram avaliados 89 deficientes auditivos de três escolas especiais da cidade de São Paulo e 11 do setor de Audiologia Educacional da Faculdade de Medicina da Universidade de São Paulo através de alguns testes audiológicos: imitanciometria, audiometria tonal limiar (ATL), emissões otoacústicas (EOA) e potencial evocado auditivo do tronco-encefálico (PEATE). Resultados: Dos 100 participantes deste estudo, 99% apresentaram uma deficiência auditiva do tipo neurossensorial e em 50% o grau predominante da deficiência auditiva foi profundo, um deles não conseguiu realizar a ATL. A média de idade da suspeita dos pais foi de 15,52 meses e o diagnóstico clínico foi de 25,07 meses, em todos os grupos a suspeita dos pais foi anterior ao diagnóstico. Apenas um participante apresentou avaliações comportamentais incompatíveis com as eletrofisiólogicas, todavia, no decorrer da pesquisa o quadro foi modificado, sendo que a flutuação da audição foi o fator mais marcante observado. Conclusões: Os resultados sugerem que a NA é um transtorno raro mesmo na população dos deficientes auditivos e alertam para a necessidade de acompanhar longitudinalmente os casos de suspeita do transtorno / Introduction: Auditory Neuropathy/Auditory Dys-synchrony (AN) is a disorder identified only 20 years ago. Due to diagnosis failure, patients with this disorder were diagnosed as hearing impaired. AN diagnosis was made possible upon the appearance of OAE\'s recordings and its presence in hearing evaluation battery. Therefore, it is possible that some individuals who have been diagnosed as suffering from sensorioneural hearing loss had indeed AN. Purpose: The purpose of this study was to characterize the type and degree of auditory impairment in a population of the hearing impaired in the city of São Paulo; to verify when parents had the suspicious of the hearing impairment and when was the audiological diagnosis done in these individuals; to identify the subjects whose behavioral evaluations are not compatible with the electrophysiological evaluations in order to identify Auditory Neuropathy events and carry out a qualitative study of the cases of subjects with incompatibility of responses in the behavioral and electrophysiological evaluations. Method: 89 hearing impaired individuals from three school for the deaf in the city of São Paulo, and 11 from the Educational Audiology Division of the Medicine School of the University of São Paulo were evaluated in some audiological tests: imitanciometry, audiometer evaluation (AE), otoacoustic emissions (OAE) and Auditory Brainstem Response (ABR). Results: Out of the 100 subjects in this study, 99% presented a sensorioneural hearing loss, and in 50% the predominant degree of auditory loss was profound, one of the subjects was not able to perform AE. The average age of parents suspicion was 15.52 months and the clinical diagnosis was 25.07 months, in all the groups the parents suspicion was prior to the formal diagnosis. Only one subject presented behavioral evaluations incompatible with the electrophysiological, however, in the course of the research the chart was changed, whereas the hearing fluctuation was the most remarkable factor observed. Conclusions: The results suggest that AN is a rare disorder even in the hearing impaired community and alert the need of long term follow up in the cases of suspected disorder

Introdução: A Neuropatia auditiva/Dessincronia auditiva (NA) é um transtorno que foi identificado há apenas 20 anos, os pacientes que possuíam este transtorno eram diagnosticados como deficientes auditivos como conseqüência da falha no diagnóstico. Com o surgimento do registro das Emissões Otoacústicas e sua presença no repertório de testes de avaliação auditiva, foi possível ao clínico fazer o diagnóstico de NA. Assim sendo, é possível que alguns indivíduos que foram diagnosticados como portadores de uma perda auditiva neurossensorial, tivessem, na verdade, NA. Objetivos: O objetivo deste estudo foi caracterizar o tipo e grau da deficiência auditiva em uma população de deficientes auditivos da cidade de São Paulo; verificar a época da suspeita pelos pais da deficiência auditiva bem como do diagnóstico audiológico nestes indivíduos; identificar os participantes cujas avaliações comportamentais são incompatíveis com as avaliações eletrofisiológicas, visando identificar casos de Neuropatia Auditiva e realizar estudo qualitativo de casos dos participantes com incompatibilidade de respostas nas avaliações comportamentais e eletrofisiológicas. Método: Foram avaliados 89 deficientes auditivos de três escolas especiais da cidade de São Paulo e 11 do setor de Audiologia Educacional da Faculdade de Medicina da Universidade de São Paulo através de alguns testes audiológicos: imitanciometria, audiometria tonal limiar (ATL), emissões otoacústicas (EOA) e potencial evocado auditivo do tronco-encefálico (PEATE). Resultados: Dos 100 participantes deste estudo, 99% apresentaram uma deficiência auditiva do tipo neurossensorial e em 50% o grau predominante da deficiência auditiva foi profundo, um deles não conseguiu realizar a ATL. A média de idade da suspeita dos pais foi de 15,52 meses e o diagnóstico clínico foi de 25,07 meses, em todos os grupos a suspeita dos pais foi anterior ao diagnóstico. Apenas um participante apresentou avaliações comportamentais incompatíveis com as eletrofisiólogicas, todavia, no decorrer da pesquisa o quadro foi modificado, sendo que a flutuação da audição foi o fator mais marcante observado. Conclusões: Os resultados sugerem que a NA é um transtorno raro mesmo na população dos deficientes auditivos e alertam para a necessidade de acompanhar longitudinalmente os casos de suspeita do transtorno / Introduction: Auditory Neuropathy/Auditory Dys-synchrony (AN) is a disorder identified only 20 years ago. Due to diagnosis failure, patients with this disorder were diagnosed as hearing impaired. AN diagnosis was made possible upon the appearance of OAE\'s recordings and its presence in hearing evaluation battery. Therefore, it is possible that some individuals who have been diagnosed as suffering from sensorioneural hearing loss had indeed AN. Purpose: The purpose of this study was to characterize the type and degree of auditory impairment in a population of the hearing impaired in the city of São Paulo; to verify when parents had the suspicious of the hearing impairment and when was the audiological diagnosis done in these individuals; to identify the subjects whose behavioral evaluations are not compatible with the electrophysiological evaluations in order to identify Auditory Neuropathy events and carry out a qualitative study of the cases of subjects with incompatibility of responses in the behavioral and electrophysiological evaluations. Method: 89 hearing impaired individuals from three school for the deaf in the city of São Paulo, and 11 from the Educational Audiology Division of the Medicine School of the University of São Paulo were evaluated in some audiological tests: imitanciometry, audiometer evaluation (AE), otoacoustic emissions (OAE) and Auditory Brainstem Response (ABR). Results: Out of the 100 subjects in this study, 99% presented a sensorioneural hearing loss, and in 50% the predominant degree of auditory loss was profound, one of the subjects was not able to perform AE. The average age of parents suspicion was 15.52 months and the clinical diagnosis was 25.07 months, in all the groups the parents suspicion was prior to the formal diagnosis. Only one subject presented behavioral evaluations incompatible with the electrophysiological, however, in the course of the research the chart was changed, whereas the hearing fluctuation was the most remarkable factor observed. Conclusions: The results suggest that AN is a rare disorder even in the hearing impaired community and alert the need of long term follow up in the cases of suspected disorder

In vivo proton magnetic resonance spectroscopy (1H MRS) is the only method available to measure small-molecule metabolites in living human tissue, including the brain, without ionizing radiation or invasive medical procedures. Despite its attendant potential for supporting clinical diagnostics in a range of neurological and psychiatric conditions, the metabolite concentration estimates produced by 1H-MRS experiments, and therefore their sensitivity and specificity to any particular biological phenomenon under study, are readily distorted by a number of confounds. These include but are not limited to static and radiofrequency field characteristics, signal relaxation dynamics, macromolecule and lipid contributions to the spectral baseline, spectral fitting artifacts, and other uncontrolled idiosyncrasies of 1H-MRS data acquisition, processing, and quantification. Using 1H-MRS data obtained via 3-Tesla and 7-Tesla magnetic resonance (MR) scanners from healthy controls, individuals with progressive and relapsing-remitting multiple sclerosis (MS), and individuals with post-traumatic stress disorder (PTSD) and/or major depressive disorder (MDD), this work therefore aims to build and apply a framework for quantifying and thereby reducing such confounds introduced to 1H-MRS estimates of in vivo metabolite concentrations at the steps of data processing and quantification, with an ultimate aim to maximizing the potential of 1H MRS for supporting sensitive and specific clinical diagnosis of neurological or psychiatric disease. The steps examined include spectral quantification by linear combination modeling (Chapter 2), absolute quantification by internal concentration referencing (Chapter 3), and cross-sectional statistical analysis of results (Chapters 4 and 5). Chapter 2 designs and implements a graphical user interface (GUI)-supported validation pipeline for measuring how data quality, spectral baseline, and baseline model affect the precision and accuracy of 1H-MR spectral quantification by linear combination modeling. This validation pipeline is then used to show that spectral data quality indices signal to noise ratio (SNR) and full width at half maximum (FWHM) interact with spectral baseline to influence not only the precision but also the accuracy of resultant metabolite concentration estimates, with fit residuals poorly indicative of true fit error and spectral baselines modeled as regularized cubic splines not significantly outperformed by those employing simulated macromolecules. A novel method for extending the commonly used spectral quantification precision estimate Cramér-Rao Lower Bound (CRLB) to incorporate considerations of continuous and piecewise polynomial baseline shapes is therefore presented, tested, and similarly integrated into a GUI-supported toolkit to improve the correspondence between estimated CRLB and metabolite fit error variability when this now empirically justified approach to spectral baseline modeling is used. In Chapter 3, age- and disease-associated differences in transverse (T2) water signal relaxation measured at 7 Tesla in the prefrontal cortex of individuals with progressive (N=21) relative to relapsing-remitting (N=26) or no (N=25) multiple sclerosis are shown to influence absolute quantification of metabolite concentrations by internal referencing to water. In Chapter 4, these findings from Chapters 2 and 3 are used to justify an evidence-based 1H-MR spectral processing and quantification protocol that focuses optimization efforts on baseline modeling approach and references metabolite concentration estimates to internal creatine instead of water. When this protocol is applied to 7-Tesla prefrontal cortex 1H-MR spectra from the aforementioned multiple sclerosis and control cohorts, it supports metabolite concentration estimates that, in the absence of any additional supporting data, inform supervised-learning-enabled identification of progressive multiple sclerosis at nearly 80% held-out validation sensitivity and specificity. Finally, in Chapter 5, the same processing, quantification, and machine-learning pipeline employed in Aim 3 is independently applied to a new set of 7-Tesla prefrontal cortex 1H-MRS raw data from an entirely different cohort of individuals with (N=20) and without (N=18) PTSD and/or comorbid or primary MDD. Here the processing, quantification, and statistics procedures designed using lessons in Chapters 2 and 3 and optimized for classifying multiple sclerosis phenotype in Chapter 4 generalize directly to metabolite-only classification of PTSD and/or MDD with sensitivity and specificity similarly near to or greater than 80%. In both Chapters 4 and 5, supervised learning avoids dimensionally reducing metabolite feature sets in order to pinpoint the specific metabolites most informative for identifying each disease group. Taken together, these findings justify the potential and continued development of 1H MRS, at least as applied in the human brain and especially as supported by multivariate approaches including supervised learning, as an auxiliary or mainstay of clinical diagnostics for neurological or psychiatric disease.

Neurological disorders present a significant challenge in global health. With the increasing availability of imaging datasets and the development of precise machine learning models, early and accurate diagnosis of neurological conditions is a promising and active area of research. However, several characteristic factors in neurology domains, such as heterogeneous imaging, inaccurate labels, or limited data, act as bottlenecks in using deep learning on clinical neuroimaging. Given these circumstances, this dissertation attempts to provide a guideline, proposing several methods and showcasing successful implementations in broad neurological conditions, including epilepsy and neurodegeneration. Methodologically, a particular focus is on comparing a two-dimensional approach as opposed to three-dimensional neural networks. In most clinical domains of neurological disorders, data are scarce and signals are weak, discouraging the use of 3D representation of raw scan data. This dissertation first demonstrates competitive performances with 2D models in tuber segmentation and AD comorbidity detection. Second, the potentials of ensemble learning are explored, further justifying the use of 2D models in the identification of neurodegeneration. Lastly, CleanNeuro is introduced in the context of 2D classification, a novel algorithm for denoising the datasets prior to training. CleanNeuro, on top of 2D classification and ensemble learning, demonstrates the feasibility of accurately classifying patients with comorbid AD and cerebral amyloid angiopathy from AD controls. Methods presented in this dissertation may serve as exemplars in the study of neurological disorders using deep learning and clinical neuroimaging. Clinically, this dissertation contributes to improving automated diagnosis and identification of regional vulnerabilities of several neurological disorders on clinical neuroimaging using deep learning. First, the classification of patients with Alzheimer’s disease from cognitively normal group demonstrates the potentials of using positron emission tomography with tau tracers as a competitive biomarker for precision medicine. Second, the segmentation of tubers in patients with tuberous sclerosis complex proves a successful 2D modeling approach in quantifying neurological burden of a rare yet deadly disease. Third, the detection of comorbid pathologies from patients with Alzheimer’s disease is analyzed and discussed in depth. Based on prior findings that comorbidities of Alzheimer’s disease affect the brain structure in a distinctive pattern, this dissertation proves for the first time the effectiveness of using deep learning on the accurate identification of comorbid pathology in vivo. Leveraging postmortem neuropathology as ground truth labels on top of the proposed methods records competitive performances in comorbidity prediction. Notably, this dissertation discovers that structural magnetic resonance imaging is a reliable biomarker in differentiating the comorbid cereberal amyloid angiopathy from Alzheimer’s disease patients. The dissertation discusses experimental findings on a wide range of neurological disorders, including tuberous sclerosis complex, dementia, and epilepsy. These results contribute to better decision-making on building neural network models for understanding and managing neurological diseases. With the thorough exploration, the dissertation may provide valuable insights that can push forward research in clinical neurology.