Esclerose multipla : correlação clinica, liquido cefalorraquiano e neuroimagem

Orientador: Benito Pereira DamascenoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: A esclerose múltipla (EM) é uma doença crônica do sistema nervoso central (SNC) de etiologia desconhecida cujas manifestações iniciais ocorrem na adolescência e no adulto jovem, secundárias à desmielinização multifocal por mecanismo autoimune e inflamatório. O curso clínico pode assumir a forma surto-remissão, progressão secundária, progressão primária. O diagnóstico é feito com base no quadro clínico evolutivo com o suporte dos exames de líquor, potencial evocado visual, ressonância magnética de crânio e medula, excluindo-se outras doenças de natureza inflamatória ou infecciosa. O exame de líquor na EM mostra pleocitose linfomonocitária, elevação do índice de IgG (imunoglobulina G) e presença de bandas oligoclonais. O quociente de albumina é alterado infrequentemente na doença. A ressonância magnética mostra lesões de hipersinal em seqüências T2, DP e FLAIR (Fluid-attenuated inversion recovery magnetic resonance imaging) e hipossinal em T1 na substância branca cerebral, nervo óptico, tronco cerebral e medula espinal. A captação de contraste indica lesão recente. O propósito do presente trabalho foi o de avaliar as correlações entre número de células no liquor, índice de IgG, síntese diária intratecal de IgG (imunoglobulina G), a presença de bandas oligoclonais com: o volume de lesão em FLAIR, T1 e T1 com contraste, e com a área de lesão em contato com espaço liquórico em FLAIR, T1 e T1 com contraste e o grau de incapacidade medido pela EDSS (escala de incapacidade expandida de Kurtzke), a forma clínica, duração da doença, cor da pele e idade dos pacientes. Setenta e um pacientes com esclerose múltipla clinicamente definida, pelos critérios de Poser, foram submetidos a exame de líquor com contagem de células, dosagem de IgG e albumina por nefelometria e cálculo do índice de IgG, síntese diária intratecal de IgG e quociente de albumina. Os dados clínicos: idade, raça, duração da doença, forma clínica e EDSS foram definidos após anamnese e exame neurológico. O volume de lesões em FLAIR, T1 e T1 com contraste foi estimado por estereologia. A área de lesão em contato com espaço liquórico foi obtida manualmente medindo-se a extensão da área lesionada em contato com a parede ventricular, superfície externa do tronco cerebral e córtex cerebral e multiplicando-se pela espessura dos cortes. Dos 71 pacientes, 62 tiveram RM de crânio com imagens em FLAIR, 56 pacientes tiveram analisadas as imagens em T1 sem contraste e 26 pacientes com imagens em T1 com contraste. Os resultados mostraram média de idade maior nas formas progressivas, maior índice de IgG na forma surto remissão, maior freqüência de bandas oligoclonais exclusivas no líquor nos casos com maior síntese diária intratecal de IgG. Quanto maior o EDSS mais elevado o quociente de albumina e a síntese diária de IgG. A área de lesão que toca o espaço liquórico foi diretamente proporcional ao quociente de albumina, sugerindo que as áreas desnudas de lesão em torno do sistema LCR é que determinam uma maior entrada de albumina, mas não de IgG, ao sistema LCRAbstract: Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) of unknown aetiology, which first manifestations occur in adolescence or in young adulthood, after multifocal demyelination caused by an autoimmune and inflammatory process. The clinical evolutive sequence can take the relapsing-remitting, secondarily progressive and primary progression forms. Diagnosis is based on the evolutive clinical manifestations, supported by cerebrospinal fluid (CSF), visual evoked responses, brain and spinal cord magnetic resonance images, with exclusion of other inflammatory or infectious diseases. The CSF analysis in MS shows lymphocyte and monocytes pleocytosis, increase in intrathecal immunoglobulin G (IgG) synthesis and the presence of oligoclonal bands. The albumin quotient is seldom changed in the disease. Magnetic resonance imaging (MR) shows hyperintensities in T2 weight, proton density (PD) and fluid-attenuated inversion recovery (FLAIR) images and hypointensity in T1 weight images, in the cerebral white matter, optic nerves, brainstem and spinal cord . The acute lesions show enhancement with contrast. The purpose of this thesis was to evaluate the correlations between the number of cells in the liquor, the IgG index, the daily intrathecal IgG synthesis, the presence of oligo-clonal bands with: the lesion volume in FLAIR, T1 and T1 with contrast and with the lesion area in contact with the CSF space in FLAIR, T1 and T1 with contrast and the degree of disability measured by EDSS (Kurtzke¿s expanded disability scale), clinical forms, duration of the disease, race and age of patients. Seventy-one patients with clinically defined multiple sclerosis, according to Poser's criteria, had CSF analysis done with cell counting, IgG and albumin dosage by means of nephelometry and calculation of the IgG index, the daily IgG intrathecal synthesis and the albumin quotient. The clinical data: age, race, duration of the disease, clinical form and EDSS were defined after anamnesis and neurological examination. The volume of lesions in FLAIR, T1 and T1 with contrast was measured by means of stereology. The lesion area in contact with the CSF space was calculated measuring manually the extension of the injured area on the ventricular wall, on the external surface of the brainstem and on the cerebral cortex and multiplying this figure by the thickness of the slices. Of the 71 patients, 62 of them were examined by brain MR with images in FLAIR, 56 patients had images in T1 without contrast analysed and 26 patients, T1 with contrast. The results showed a higher age average in the progressive forms, a greater IgG index in the relapsing-remitting form, a higher frequency of the exclusive oligoclonal bands in the CSF, in the cases with a greater daily intratechal synthesis of IgG. The greater the EDSS, the higher was the albumin quotient and the daily synthesis of IgG. The lesion area that contacts the CSF space was directly proportional to the albumin quotient, what suggests that the lesion areas around the CSF system determine a greater input of albumin, but not IgG, in the CSF systemDoutoradoNeurologiaDoutor em Ciências Médica

Safety Of Switching From Natalizumab Straight Into Fingolimod In A Group Of Jcv-positive Patients With Multiple Sclerosis

To assess safety of the switch between natalizumab and fingolimod without a washout period. Methods: Prospective data on 25 JCV positive patients who underwent this medication switch were collected and analyzed. Results: After a median period of nine months from the medication switch, there were no safety issues to report. The patients had good disease control and no adverse events were reported. Conclusion: Washout may not be necessary in daily practice when switching from natalizumab to fingolimod. Expertise on multiple sclerosis management, however, is essential for drug switching.74865065

Segurança na mudança direta de natalizumabe para fingolimode em um grupo de pacientes com esclerose múltipla e positivos para JCV

To assess safety of the switch between natalizumab and fingolimod without a washout period. Methods Prospective data on 25 JCV positive patients who underwent this medication switch were collected and analyzed. Results After a median period of nine months from the medication switch, there were no safety issues to report. The patients had good disease control and no adverse events were reported. Conclusion Washout may not be necessary in daily practice when switching from natalizumab to fingolimod. Expertise on multiple sclerosis management, however, is essential for drug switching748650652Avaliar a segurança na mudança entre natalizumabe e fingolimode sem período de washout. Métodos Dados prospectivos de 25 pacientes positivos para vírus JC que tiveram sua medicação modificada foram coletados e analisados. Resultados Após uma mediana de nove meses da troca de medicação, não havia aspectos de segurança a relatar. Os pacientes estavam com bom controle da doença e não foram relatados eventos adversos. Conclusão Washout pode não ser necessário na prática diária para a mudança entre natalizumabe e fingolimode. No entanto, expertise no manejo de esclerose múltipla é essencial para esta troca entre medicaçõe

Relato de um caso com rápida evolução e desfecho satisfatório em criança com provável Síndrome de Guillain- Barré

Introduction: Guillain-Barré Syndrome (GBS) is the most frequent cause of acute and sub-acute flaccid paralysis after polio eradication. Although rare, it is recognized as the leading cause of flaccid paralysis among the admissions to pediatric intensive care for acute neuromuscular diseases. Objective: To report the case of a 14-month-old male patient with a probable diagnosis of GBS with acute, myelinated motor sensitive neuropathy, with probable secondary axonal involvement, with rapid clinical recovery. Case Report: A male patient admitted in a reference hospital in the Federal District, Brazil, residing in the Integrated Development Region of the Federal District and Surroundings. The child was 14 months old and 8.6 kg, with an updated vaccination status and neuropsychomotor development appropriate for his age, with a condition of paresis in the lower limbs, without cognitive changes. After 14 hours of admission, due to the worsening of his clinical situation and the albumino-cytological dissociation identified by the analysis of cerebrospinal fluid, it was started immunotherapy with intravenous human immunoglobulin, 0.7g/kg/day for three days. Twenty four hours after start of treatment, the child showed a clinical improvement of his general condition. The patient was discharged after five days of hospitalization. After 76 days of discharge, there was a significant improvement in neuropsychomotor development, despite a slight delay in its development. Conclusion: Due to the rarity of Guillain-Barré Syndrome among young children, it is important that health professionals remain sensitive to capture and treat unusual cases in a timely manner. We also recommend that the identified cases be monitored carefully, in order to check if the Guillain-Barré Syndrome, and its variants, can explain developmental disorders a posteriori.Introdução: A Síndrome de Guillain-Barré (SGB) é a causa mais frequente de paralisia flácida aguda e subaguda desde a erradicação da poliomielite. Embora rara, é reconhecida como a principal causa de paralisia flácida entre pessoas internadas em terapia intensiva pediátrica por doenças neuromusculares agudas. Objetivo: Relatar um caso de paciente do sexo masculino, com 14 meses de idade, com diagnóstico provável de Síndrome de Guillain-Barré com neuropatia sensitivo motora, aguda, mielínica, com provável comprometimento axonal secundário, com rápida evolução e melhora.   Descrição do caso: Foi admitido em hospital público maternoinfantil de referência para o Distrito Federal um paciente masculino, residente na Região Integrada de Desenvolvimento do Distrito Federal e Entorno. A criança tinha 14 meses de idade e 8,6kg, situação vacinal atualizada e desenvolvimentoneurospicomotor adequado para a idade, com quadro de paresia em membros inferiores, sem alterações cognitivas. Após 14 horas da admissão, diante do agravamento do quadro clínico e da dissociação albomino-citológica identificada pela análise de líquido cefalo-raquidiano foi iniciada imunoterapia (imunoglobulina humana endovenosa, 0,7g/kg/dia por três dias). Após 24 horas do início do tratamento, a criança apresentou melhora em seu estado geral. O paciente teve alta hospitalar após cinco dias de internação. Após 76 dias da alta, foi constatada melhora significativa no desenvolvimento neuropsicomotor, apesar de leve atraso em seu desenvolvimento até o momento.   Conclusão: Diante da raridade de casos em crianças, é importante que os profissionais de saúde se mantenham sensíveis a captar e tratar os casos de maneira oportuna. Recomendamos ainda que os casos identificados sejam acompanhados cuidadosamente, afim de verificar se a SGB, esuas variantes, podem explicar transtornos de desenvolvimento à posteriori

Microbicidal Action of Indole-3-Acetic Acid Combined with Horseradish Peroxidase on Prototheca zopfii from Bovine Mastitis

We investigated the toxic effect of indole-3-acetic acid (IAA) combined with horseradish peroxidase (HRP) on Prototheca zopfii from bovine mastitis. P. zopfii isolates were identified and characterized by morpho-physiological parameters; presences of P. zopfii genotype 2 were also investigated. Subsequently, P. zopfii was incubated in the absence (control) or presence of IAA/HRP and examined for: (i) cell viability; (ii) colonies number formation; (iii) antioxidant enzyme activity; and (iv) DNA integrity. Significance of differences was calculated using ANOVA and Tukey`s test (P a parts per thousand currency sign 0.05). As evidenced by Trypan blue exclusion and colony formation in Sabouraud dextrose agar, IAA/HRP addition to the culture reduced respective P. zopfii viability and P. zopfii colony formation in a concentration- and time-dependent manner. IAA/HRP specifically reduced cell viability in 10, 15, 20, 25, and 32% after 4, 6, 8, 10, and 12 h of incubation, respectively, compared with the control at the same time. The number of colony formation was inhibited (45, 82, and 88%) by IAA/HRP after 4, 6, and 9 h of incubation, respectively, compared with the control at the same time. In addition, P. zopfii antioxidant activity increased measurably in the presence of IAA/HRP (6 h); superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase increased by 90, 120, 150% and 3.4 times, compared with the controls. IAA/HRP did not appear to effect P. zopfii DNA integrity when examined by electrophoresis. In conclusion, IAA/HRP appears to function as a microbicidal mechanism on P. zopfii genotype 2 from bovine mastitis.Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP

Safety of switching from natalizumab straight into fingolimod in a group of JCV-positive patients with multiple sclerosis

ABSTRACT Objective To assess safety of the switch between natalizumab and fingolimod without a washout period. Methods Prospective data on 25 JCV positive patients who underwent this medication switch were collected and analyzed. Results After a median period of nine months from the medication switch, there were no safety issues to report. The patients had good disease control and no adverse events were reported. Conclusion Washout may not be necessary in daily practice when switching from natalizumab to fingolimod. Expertise on multiple sclerosis management, however, is essential for drug switching