Abstract not available

PhD / The aims of this study were to test the efficacy of immunoglobulin and its Fab and Fc fragment in the treatment of experimental autoimmune neuritis (EAN) in Lewis rats, to investigate which portion of immunoglobulin is operative in the effect of IVIg, and to clarify the possible mechanisms by which immunoglobulin exerts its action in the treatment of rats EAN. EAN was induced by immunization with whole bovine peripheral nerve myelin. The immunized rats were randomized into groups, assessed clinically, electrophysiologically, and histologically, and intravenously injected with normal saline, albumin, human IVIg preparation, purified Fab or Fc fragments. The treatment efficacy was compared between normal saline and albumin groups, albumin and IVIg groups, albumin and Fab groups, albumin and Fc groups, Fab and Fc groups, Fab and IVIg groups, and Fc and IVIg groups. Methods of myelin isolation, antibody purification, and Western blot techniques were also applied. The results revealed that treatment with Fc fragment and IVIg at the onset of signs of disease effectively prevented further progression of disease, shortened disease duration, and facilitating recovery from illness as shown in clinical, electrophysiological and histological parameters. In the study which the efficacy of albumin and IVIg was compared, 5 out of 17 rats (29%) in the albumin group and 12 out of 17 (71%) in the IVIg group completely recovered from the clinical disease by day 30. The animals receiving IVIg treatment exhibited lower clinical scores, less prolongation of S wave latencies, better maintained S wave amplitudes, less reduction of distal motor NCVs, better maintained distal and proximal CMAP amplitudes, and lower histological grades. In the study which the efficacy of albumin, Fab fragment, Fc fragment, and IVIg was compared, 0 out of 8 (0%) in the albumin group, 1 out of 8 (13%) in the Fab group, 4 out of 8 (50%) in the Fc group, and 6 out of 9 (67%) rats in the IgG group completely recovered from the clinical disease by day 30. The animals receiving Fc fragment and IVIg treatment exhibited lower clinical scores, less prominent weight loss, less prolongation of S wave latencies, better maintained S wave amplitudes, less reduction of distal motor NCVs, better maintained distal and proximal CMAP amplitudes, and lower histological grades.

Background: Cryptococcal induced visual loss is common and increasingly becoming a debilitating consequence in survivors of cryptococcal meningitis (CM). Conflicting reports of the optic neuritis and papilloedema models of visual loss have delayed the introduction of effective interventional strategies for prevention and treatment of visual loss in CM. Qualitative and quantitative diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) of the optic nerves have proven useful in the examination of the microstructure of the optic nerve especially in optic neuritis. Its application has been extrapolated to other optic nerve disorders such as ischaemic optic neuropathy and glaucoma. The aim of this study is to elucidate the pathogenesis of cryptococcal-induced visual loss using diffusion imaging of the optic nerve as an investigational tool. Method: Full ethical approval was obtained from the Greys Hospital, Department of Health and University of KwaZulu Natal Ethics Committees. Reliable and reproducible optic nerve diffusion techniques were first developed and optimized on 29 healthy volunteers at Greys Hospital, Neurology and Radiology departments using a Philips 1.5 Tesla Gyroscan. Informed consent was also obtained from 95 patients suffering from CM (≥18 yrs. of age), 14 patients with papilloedema and 14 patients with optic neuritis from other causes, recruited from Greys and Edendale Hospitals. Patients underwent full neuro-ophthalmological assessments, CSF examination, haematological workup, CD4 count, (viral load for some), electrophysiological assessment of vision [Visual evoked potential (VEP) and Humphreys visual fields (HVF)], Magnetic Resonance Imaging (MRI) scan of the brain and orbits and DWI and DTI of the optic nerves. Results and Discussion: Visual loss is common in CM, occurring in 34.6-48%. Optic neuritis was uncommon as evidenced by a lack of signal change and lack of enhancement within the optic nerve in all patients scanned. The peri-optic CSF space was not dilated and the optic nerve diameter was not increased regardless of CSF pressure and visual status. Swollen optic discs occurred in only 25% of patients whereas raised intracranial pressure (> 20cmCSF) was demonstrated in 69-71% of patients. Therefore visual loss could not be explained by papilloedema alone. The VEP P100 latency was shown to be a useful screening test for subclinical optic nerve disease in CM, but HVF was not. The optic nerve diffusion imaging used was reliable and reproducible and produced diffusion parameters equivalent to other investigators in the field. Neither optic nerve movement nor the CSF signal was demonstrated to impact significantly on optic nerve diffusion parameters. Optic nerve diffusion imaging did not demonstrate similarities between CM and papilloedema or optic neuritis regardless of CSF pressure or vision. Conclusion: The rarity of optic neuritis in CM and the disparity between papilloedema and visual loss together with the lack of support from diffusion studies suggest a 3rd mechanism of visual loss viz. the optic nerve compartment syndrome. Good clinical support is provided by a case report for this hypothesis that shows re-opening of the peri-optic CSF space and return of the peri-optic CSF signal on MRI with lowering of intracranial pressure and antifungal treatment. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2013.

PhD / The aims of this study were to test the efficacy of immunoglobulin and its Fab and Fc fragment in the treatment of experimental autoimmune neuritis (EAN) in Lewis rats, to investigate which portion of immunoglobulin is operative in the effect of IVIg, and to clarify the possible mechanisms by which immunoglobulin exerts its action in the treatment of rats EAN. EAN was induced by immunization with whole bovine peripheral nerve myelin. The immunized rats were randomized into groups, assessed clinically, electrophysiologically, and histologically, and intravenously injected with normal saline, albumin, human IVIg preparation, purified Fab or Fc fragments. The treatment efficacy was compared between normal saline and albumin groups, albumin and IVIg groups, albumin and Fab groups, albumin and Fc groups, Fab and Fc groups, Fab and IVIg groups, and Fc and IVIg groups. Methods of myelin isolation, antibody purification, and Western blot techniques were also applied. The results revealed that treatment with Fc fragment and IVIg at the onset of signs of disease effectively prevented further progression of disease, shortened disease duration, and facilitating recovery from illness as shown in clinical, electrophysiological and histological parameters. In the study which the efficacy of albumin and IVIg was compared, 5 out of 17 rats (29%) in the albumin group and 12 out of 17 (71%) in the IVIg group completely recovered from the clinical disease by day 30. The animals receiving IVIg treatment exhibited lower clinical scores, less prolongation of S wave latencies, better maintained S wave amplitudes, less reduction of distal motor NCVs, better maintained distal and proximal CMAP amplitudes, and lower histological grades. In the study which the efficacy of albumin, Fab fragment, Fc fragment, and IVIg was compared, 0 out of 8 (0%) in the albumin group, 1 out of 8 (13%) in the Fab group, 4 out of 8 (50%) in the Fc group, and 6 out of 9 (67%) rats in the IgG group completely recovered from the clinical disease by day 30. The animals receiving Fc fragment and IVIg treatment exhibited lower clinical scores, less prominent weight loss, less prolongation of S wave latencies, better maintained S wave amplitudes, less reduction of distal motor NCVs, better maintained distal and proximal CMAP amplitudes, and lower histological grades.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Made available in DSpace on 2014-06-11T19:29:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-08-28Bitstream added on 2014-06-13T19:38:42Z : No. of bitstreams: 1 longo_fr_me_botfm.pdf: 199438 bytes, checksum: 5570cb34fea1a50aaeccfeb828712466 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A hanseníase é uma doença crônica que de um modo geral compromete a parte dermatológica e neurológica de um indivíduo, sendo que as alterações neurológicas, quando não diagnosticadas e tratadas adequadamente, podem levar a deformidades, causando incapacidades físicas. Realizou-se estudo retrospectivo utilizando-se de registros médicos de pacientes de hanseníase atendidos no Ambulatório da Faculdade de Medicina de Botucatu - UNESP. No total de 150 pacientes com diagnóstico confirmado, 48 (32 %), apresentaram neurites e, dentre estes, 28 (58,33 %) apresentaram reações, 17 (35,42 %) lesões neurológicas e lesões conseqüentes a estas. O objetivo principal foi avaliar a qualidade do atendimento dispensado pela equipe multiprofissional que acompanha estes pacientes, quanto à prevenção de incapacidades físicas entre doentes provenientes de outros serviços e dos diagnosticados no referido Ambulatório. Observou-se que os pacientes provenientes de outros serviços foram os que mais apresentaram seqüelas (94,12 %), mais episódios reacionais (60,71 %) e neurites (66,66 %). Concluiu-se que a prevenção de incapacidades ocorreu de modo mais efetivo em um serviço que conta com equipe multiprofissional especializada. / Leprosy is a chronic illness that in a general way compromises the dermatological and neurological part of an individual, being that the neurological alterations, when not diagnostic and treated adequately, can take the deformities, causing disabilities. Retrospective study using itself of medical registers of taken care of patients of leprosy in the Clinic of the College of Medicine of Botucatu - UNESP was become follow-up. In the total of 150 patients with confirmed diagnosis, 48 (32%), had presented neuritis and, amongst these, 28 (58.33%) had presented reactions, 17 (35.42%) neurological injuries and consequent injuries to these. The main objective was to evaluate the quality of the attendance excused for the multi-professional team that follows these patients, how much to the prevention of disabilities between sick people proceeding from other services and of the diagnostic ones in the related Clinic. It was observed that the patients proceeding from other services had been the ones that had more presented sequels (94.12%), more reactions episodes (60.71%) and neuritis (66.66%). One concluded that the prevention of incapacities occurred in more effective way in a service that specialized multi-professional counts on team.

Orientador: Joel Carlos Lastória / Banca: Jorge Antonio de Almeida / Banca: Jairo Aparecido Ayres / Resumo: A hanseníase é uma doença crônica que de um modo geral compromete a parte dermatológica e neurológica de um indivíduo, sendo que as alterações neurológicas, quando não diagnosticadas e tratadas adequadamente, podem levar a deformidades, causando incapacidades físicas. Realizou-se estudo retrospectivo utilizando-se de registros médicos de pacientes de hanseníase atendidos no Ambulatório da Faculdade de Medicina de Botucatu - UNESP. No total de 150 pacientes com diagnóstico confirmado, 48 (32 %), apresentaram neurites e, dentre estes, 28 (58,33 %) apresentaram reações, 17 (35,42 %) lesões neurológicas e lesões conseqüentes a estas. O objetivo principal foi avaliar a qualidade do atendimento dispensado pela equipe multiprofissional que acompanha estes pacientes, quanto à prevenção de incapacidades físicas entre doentes provenientes de outros serviços e dos diagnosticados no referido Ambulatório. Observou-se que os pacientes provenientes de outros serviços foram os que mais apresentaram seqüelas (94,12 %), mais episódios reacionais (60,71 %) e neurites (66,66 %). Concluiu-se que a prevenção de incapacidades ocorreu de modo mais efetivo em um serviço que conta com equipe multiprofissional especializada. / Abstract: Leprosy is a chronic illness that in a general way compromises the dermatological and neurological part of an individual, being that the neurological alterations, when not diagnostic and treated adequately, can take the deformities, causing disabilities. Retrospective study using itself of medical registers of taken care of patients of leprosy in the Clinic of the College of Medicine of Botucatu - UNESP was become follow-up. In the total of 150 patients with confirmed diagnosis, 48 (32%), had presented neuritis and, amongst these, 28 (58.33%) had presented reactions, 17 (35.42%) neurological injuries and consequent injuries to these. The main objective was to evaluate the quality of the attendance excused for the multi-professional team that follows these patients, how much to the prevention of disabilities between sick people proceeding from other services and of the diagnostic ones in the related Clinic. It was observed that the patients proceeding from other services had been the ones that had more presented sequels (94.12%), more reactions episodes (60.71%) and neuritis (66.66%). One concluded that the prevention of incapacities occurred in more effective way in a service that specialized multi-professional counts on team. / Mestre

Nos Ãltimos anos, a prevalÃncia da hansenÃase no Brasil vem sendo reduzida, entretanto, o nÃmero de pessoas com incapacidades resultantes de neurite crÃnica continua alto. O tratamento padrÃo da neurite hansÃnica se constitui de corticoterapia oral. Em casos resistentes à corticoterapia, pode ser realizada intervenÃÃo cirÃrgica descompressiva, denominada neurolise. Dados sobre a efetividade da neurolise sÃo escassos na literatura. Com o objetivo de avaliar o dÃficit sensitivo-motor antes e apÃs neurolise, realizou-se um estudo retrospectivo. Foram incluÃdos portadores de hansenÃase submetidos à neurolise na referÃncia estadual de RondÃnia, nos anos de 2000 a 2003. Dados sÃcio-demogrÃficos e clÃnicos foram coletados do livro de registro de cirurgias do hospital, dos prontuÃrios e da base de dados do Sistema Nacional de Agravos de NotificaÃÃo. Para avaliar o grau de comprometimento sensitivo e motor, foram criados escores ordinais baseadas nas avaliaÃÃes clÃnicas . Dos 118 indivÃduos incluÃdos, que foram submetidos a 297 neurolises, 74 (62,7%) eram do sexo masculino, noventa e seis (81,4%) foram classificados como portadores da forma clÃnica dimorfa. Somente (53,4%) estavam em tratamento com poliquimioterapia no momento da cirurgia. A mediana do tempo entre o primeiro episÃdio de neurite e a neurolise foi de um ano (mÃximo = 12,3 anos). A mediana do escore semi-quantitativo sensitivo diminuiu de 5 para 3 (nervo ulnar), de 3 para 2 (nervo mediano), e de 9,5 para 7,5 (nervo tibial posterior; todos p<0,001). Noventa por cento dos pacientes com dÃficit sensitivo grave do nervo ulnar antes da cirurgia apresentaram um escore melhor apÃs a cirurgia. Na anÃlise, um escore sensitivo alto do nervo ulnar (OR ajustada = 1,9; IC 95%: 1,37 â 2,65; p<0,001) e do nervo tibial posterior antes da cirurgia (OR ajustada = 1,2; IC 95%: 1,02 â 1,39; p = 0,02), aumentaram a chance da melhora. O tempo entre o primeiro perÃodo de neurite e a cirurgia nÃo modificou o resultado clÃnico de forma significativa. Similar à avaliaÃÃo sensitiva, o escore motor dos nervos ulnar e fibular melhorou significativamente (ulnar: p = 0,03; fibular: p<0,001). Quase 60% dos pacientes submetidos à neurolise no nervo fibular apresentaram maior forÃa muscular apÃs a cirurgia. Os dados do estudo indicam que a neurolise à benÃfica em casos de neurite hansÃnica, mesmo apÃs um perÃodo prolongado de neurite. Faz-se necessÃrio elaborar estratÃgias para aperfeiÃoar a terapia da neurite hansÃnica com Ãnfase no monitoramento da funÃÃo neural. / In Brazil, the prevalence of leprosy has been reduced in the last years. However, there are still many people living with disabilities, resulting from chronic leprosy neuritis. Oral corticosteroid therapy is the standard treatment of neuritis. In case of unsuccessful treatment, a surgery, the so-called neurolysis, or external decompression, may be indicated. Data about the effectiveness of neurolysis are scanty. To assess the degree of sensory and motor loss before and after neurolysis, we performed a retrospective study. Leprosy patients were included, that had received neurolysis of peripheral nerve trunks in the reference hospital of RondÃnia State (North Brazil), between 2000 and 2003. Socio-demographic and clinical data were collected from the hospitalâs registry of surgeries, from patientsâ charts and from the Notifiable Diseases Database (âSistema Nacional de InformaÃÃo de Agravos de NotificaÃÃoâ). To assess the degree of sensory and motor deficiencies, we created an ordinal score based on the clinical evaluations. Of the 118 individuals included (in total 297 neurolyses), 74 (62,7%) were males. Ninety-six (81,4%) patients were classified clinically with borderline leprosy. Only (53,4%) of the patients were under multi-drug therapy at the moment of neurolysis. The median time between the first episode of neuritis and the surgery was one year (maximum = 12,3 years). The median of the score reduced from 5 to 3 (ulnar nerve), from 3 to 2 (median nerve) and from 9,5 to 7,5 (posterior tibial nerve; all p<0,001). Ninety % of patients with severe sensory deficiency before surgery presented with an improved score after neurolysis. In the multivariate analysis, only the sensitive score of the ulnar nerve (adjusted OR = 1,9; 95% CI: 1,38 â 2,65; p<0,001) and the sensitive score of the posterior tibial nerve (adjusted OR = 1,2; 95% CI: 1,02 â 1,39; p = 0,02) before surgery were factors increasing the chance of improvement. The clinical classification and the period between the first episode of neuritis and surgery did not modify the clinical result significantly. Similar to the sensory evaluation, the motor score of the ulnar and common peroneal nerves improved significantly after surgical intervention (ulnar nerve: p = 0,03; comnor peroneal nerve: p<0,001). Almost 60% of the patients operated on the common peroneal nerve presented more muscle strength. The data of the present study indicate that neurolysis is of important benefit in leprosy neuritis, even after a prolonged period of neuritis. Strategies need to be elaborated to improve the therapeutic options in the treatment of leprosy neuritis.

The field of medicine is always evolving and one step in this evolution is the use of decision support systems like artificial intelligence. These systems open the possibility to minimize human error in diagnostics as practitioners can use objective measurements and analysis to assist with the diagnosis. In this study the focus has been to explore the possibility of using deep learning models to classify stroke, vestibular neuritis and control groups based on datafrom a video head impulse test (vHIT). This was done by pre-processing data from vHIT into features that could be used as input to an artificial neural network. Three different modelswere designed, where the first two used mean motion data describing the motion of the head and eyes and their standard deviations, and the last model used extracted parameters. The models were trained from vHIT-data from 76 control cases, 37 vestibular neuritis cases and 46 stroke cases. To get a better grasp of the differences between the groups, a comparison was made between the parameters and the mean curves. The resulting models performed to a varying degree with the first model correctly classified 77.8 % of the control cases, 55.6 % of the stroke cases and 80 % of the vestibular neuritis cases. The second model correctly classified 100 % of the control cases, 11.1 % of the stroke cases and 80.0 % of thevestibular neuritis cases. Lastly the third model correctly classified 77.8 % of the control cases, 22.2 % of the stroke cases and 100 % of the vestibular neuritis cases. The results are still insufficient when it comes to clinical use, as the stroke classification requires a higher sensitivity. This means that the cases are correctly classified and gets the urgent care they need. However, with more data and research, these methods could improve further and then provide a valuable service as decision support systems.