No description available.

Atypical imaging features of multiple sclerosis lesions include size >2 cm, mass effect, oedema and/or ring enhancement. This constellation is often referred to as 'tumefactive multiple sclerosis'. Previous series emphasize their unifocal and clinically isolated nature, however, evolution of these lesions is not well defined. Biopsy may be required for diagnosis. We describe clinical and radiographic features in 168 patients with biopsy confirmed CNS inflammatory demyelinating disease (IDD). Lesions were analysed on pre- and post-biopsy magnetic resonance imaging (MRI) for location, size, mass effect/oedema, enhancement, multifocality and fulfilment of Barkhof criteria. Clinical data were correlated to MRI. Female to male ratio was 1.2: 1, median age at onset, 37 years, duration between symptom onset and biopsy, 7.1 weeks and total disease duration, 3.9 years. Clinical course prior to biopsy was a first neurological event in 61%, relapsing-remitting in 29% and progressive in 4%. Presentations were typically polysymptomatic, with motor, cognitive and sensory symptoms predominating. Aphasia, agnosia, seizures and visual field defects were observed. At follow-up, 70% developed definite multiple sclerosis, and 14% had an isolated demyelinating syndrome. Median time to second attack was 4.8 years, and median EDSS at follow-up was 3.0. Multiple lesions were present in 70% on pre-biopsy MRI, and in 83% by last MRI, with Barkhof criteria fulfilled in 46% prior to biopsy and 55% by follow-up. Only 17% of cases remained unifocal. Median largest lesion size on T2-weighted images was 4 cm (range 0.5-12), with a discernible size of 2.1 cm (range 0.5-7.5). Biopsied lesions demonstrated mass effect in 45% and oedema in 77%. A strong association was found between lesion size, and presence of mass effect and/or oedema (P < 0.001). Ring enhancement was frequent. Most tumefactive features did not correlate with gender, course or diagnosis. Although lesion size >5 cm was associated with a slightly higher EDSS at last follow-up, long-term prognosis in patients with disease duration >10 years was better (EDSS 1.5) compared with a population-based multiple sclerosis cohort matched for disease duration (EDSS 3.5; P < 0.001). Given the retrospective nature of the study, the precise reason for biopsy could not always be determined. This study underscores the diagnostically challenging nature of CNS IDDs that present with atypical clinical or radiographic features. Most have multifocal disease at onset, and develop RRMS by follow-up. Although increased awareness of this broad spectrum may obviate need for biopsy in many circumstances, an important role for diagnostic brain biopsy may be required in some cases.

Multiple Sclerosis (MS) is a chronic, inflammatory disease of the central nervous system. MS is caused by the immune-mediated destruction of myelin and oligodendrocytes, resulting in demyelination and neurodegeneration. The microRNA miR-145-5p has been demonstrated to be upregulated in MS lesions. Our lab has previously shown that dysregulation of miR-145-5p can interfere with oligodendrocyte differentiation in mice and that knockout of miR-145-5p protects mice from experimental autoimmune encephalomyelitis (EAE), a model for MS. The objective of this study is to determine if inhibition of miR-145-5p with an antisense oligonucleotide (ASO) is sufficient to protect mice from EAE. Female mice were induced with EAE and then treated with a control or miR-145 ASO at the onset of disease. We evaluated disease progression by monitoring clinical severity, and evaluating molecular and structural characteristics of EAE by RT-qPCR, histology, immunohistochemistry and electron microscopy. We have shown that the miR-145 ASO reduced miR-145-5p expression in the lumbar spinal cord, spleen and thymus following EAE induction. Treatment with the miR-145-5p ASO resulted in improved clinical severity of EAE, reduced neuroinflammation and increased myelination. Inhibition of miR-145-5p may represent a novel treatment for MS.

Orientador: Juliana Campos Junqueira / Banca: João Manoel Theotonio dos Santos / Banca: Liliana Scorzoni / Resumo: A Esclerose Múltipla (EM) é uma doença inflamatória, autoimune, crônica e desmielinizante que acomete o Sistema Nervoso Central (SNC). Sua etiologia ainda não é bem definida, mas vários fatores de risco podem estar associados à doença, incluindo fatores genéticos e ambientais. Recentemente, tem sido sugerido que a microbiota do indivíduo pode ter influência na EM. Sendo assim, o objetivo desse estudo foi investigar a relação entre EM e infecções fúngicas orais. Foram selecionados 100 indivíduos, sendo 55 com diagnóstico de EM pelos Critérios de McDonald (2017) e 45 indivíduos saudáveis (grupo controle). Amostras de saliva foram coletadas e semeadas em meios de culturas seletivos para o gênero Candida, incluindo ágar Sabouraud Dextrose com cloranfenicol e CHROMagar Candida. Após período de incubação de 48 horas, foi realizada a contagem do número de Unidades Formadoras de Colônias (UFC/mL), e as colônias isoladas foram submetidas à análise de PCR multiplex para identificação da espécie de Candida. Os resultados foram analisados pelos testes estatísticos de Qui-quadrado e Mann-Whitney, considerando-se nível de significância de 5%. Foi verificado presença de Candida spp. na cavidade bucal de 50,09% dos pacientes do grupo EM e de 35,55% dos indivíduos do grupo controle. Nos indivíduos com crescimento positivo para Candida spp., a mediana do número de colônias de Candida observadas foi de 220 UFC/mL para o grupo EM e 120 UFC/mL para o grupo controle. Entretanto, não foram observadas diferenças estatisticamente significantes entre os grupos tanto para a prevalência como contagem de UFC/mL. Em relação a identificação das espécies de Candida, foi encontrado 73,91% de C. albicans, 21,73% de C. glabrata, 2,17% de C. tropicalis e 2,17% de C. krusei. Concluiu-se que a presença de Candida spp. na cavidade bucal de indivíduos com EM foi mais elevada em relação ao grupo controle / Abstract: Multiple Sclerosis (MS) is an inflammatory, autoimmune, chronic and demyelinating disease that affects the Central Nervous System (CNS). Its etiology is not yet well defined, but several risk factors may be associated with the disease, including genetic and environmental factors. Recently, it has been suggested that the individual's microbiota may have influence on MS. Therefore, the objective of this study was to investigate the relationship between MS and oral fungal infections. A total of 100 individuals were selected, 55 of them diagnosed with MS by the McDonald Criteria (2017) and 45 healthy individuals (control group). Saliva samples were collected and seeded in culture medias selectives for the Candida genus, including Sabouraud Dextrose agar with chloramphenicol and CHROMagar Candida. After incubation period of 48 hours, the number of Colony Forming Units (CFU / mL) was counted and the colonies were isolated for identification of the Candida species by multiplex PCR. The results were analyzed by Chi-square and Mann-Whitney statistical tests considering a significant level of 5%. It was verified the presence of Candida spp. in the oral cavity of 50.09% of the patients in the MS group and 35.55% of the individuals in the control group. In individuals with positive growth for Candida spp., the median of Candida colonies observed was 220 CFU/mL for the MS group and 120 CFU/mL for the control group. However, no statistically significant differences were observed between the groups for both prevalence and CFU/mL count. In relation to the identifications of Candida species, it was found 73.91% of C. albicans, 21.73% of C. glabrata, 2.17% of C. tropicalis and 2.17% of C. krusei. It was concluded that the presence of Candida spp. in the oral cavity of individuals with MS was higher than the control group / Mestre

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12871号 / 論医博第2087号 / 新制||医||1006(附属図書館) / 31589 / 北海道大学大学院医学研究科臨床医学コース / (主査)教授 三森 経世, 教授 長澤 丘司, 教授 河野 憲二 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21020号 / 医博第4366号 / 新制||医||1028(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 椛島 健治, 教授 三森 経世, 教授 小柳 義夫 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

Multiple Sclerosis (MS) is a chronic and potentially disabling disease of the central nervous system (CNS) in which the immune system attacks the protective myelin layer that surrounds nerve cells. While the majority of individuals diagnosed with MS initially present with a non-progressive relapsing form of the disease, there is significant risk of eventually transitioning to a more progressive form for which there are few effective treatments. Consequently, early intervention with disease-modifying therapies (DMTs) is essential for effective disease management. Newly diagnosed patients are typically started on one of four first-line therapies (beta interferon, glatiramer acetate, teriflunomide, or dimethyl fumarate). Though there are distinct differences between these treatments in regard to efficacy and safety, there is no uniform standard for making decisions about which to initiate treatment with. This review gives an overview of current first-line MS therapies, and seeks to highlight the lack of comparison data and the gaps in the current understanding of disease management, as well as the need for more comprehensive research in these areas.

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS) whereby abnormal autoimmune responses cause damage to myelin, the lipid-rich layer that surrounds and insulates axons. This results in interruptions in communication within the CNS and between the CNS and peripheral nervous system (PNS). This dysfunction contributes to a variety of symptoms that negatively impact the lives of individuals with MS. Sleep disturbances and memory difficulties are two common challenges faced by MS patients, but are not comprehensively understood within the MS literature. Additionally, despite general consensus with regard to the important role that sleep plays in memory function, studies investigating the links between sleep disturbance and memory in MS are sparse. As such, the purpose of this dissertation was to determine whether sleep disturbance helps to explain differential memory functioning in individuals with MS, both cross-sectionally and over time. A sample of 165 early MS patients participated in cognitive measures, gait assessments, sensorimotor assessments, and self-report questionnaires once at baseline, and again 3 years after their initial assessment. Magnetic Resonance Imaging (MRI) data were collected at baseline. The primary predictor variable for the present study was sleep disturbance, as measured by two validated self-report measures of sleep functioning, the Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI). This study’s primary outcome was memory function, which was assessed by the CANTAB Paired Associate Learning (CANTAB PAL), Brief Visuospatial Memory Test, Revised (BVMT-R), Selective Reminding Test (SRT), and Verbal Paired Associate Learning (VPAL). Additional predictors included mood, disease burden, estimated premorbid intelligence, and demographic variables (age, sex, BMI). As hypothesized, results revealed that changes in sleep significantly predicted changes in memory over time. Patients with stable sleep and worsened sleep demonstrated an average decline in memory z-score from baseline to follow up, whereas patients whose sleep improved demonstrated an average improvement in memory z-score. Cross-sectionally, the presence of sleep disturbance significantly predicted worse memory performance when the ISI was used a measure of sleep disturbance, but not when the PSQI was used as a measure of sleep disturbance. Taken together, results highlight the importance of acknowledging sleep disturbance as an important predictor of memory function in individuals with early MS, paving the way for highly needed efforts toward prevention and intervention. However, findings should be extended to both objective and subjective sleep measures beyond the ISI.

Multiple sclerosis (MS) is the most common neurological disorder of young adulthood and is often associated with cognitive impairment and emotional dysfunction. Due to the nature of the disease, the cognitive deficits in MS are often variable in their presentation, and consist of deficits in processing speed, attention, working memory, and executive functioning. The purpose of the present study was to explore common methods of documenting MS-related cognitive deficits, to elucidate the relationship between the cognitive deficits seen in MS and physiological markers of cognitive functioning (i.e., quantitative EEG), and to analyze the relationship between cognitive deficits and mood dysfunction in MS. There were 26 participants diagnosed with remitting-relapsing multiple sclerosis and 18 age, sex, and education matched controls. Results of cognitive testing indicated deficits in gross cognitive functioning, language, attention, processing speed, working memory, and executive functioning. A MANOVA encompassing group, task (PASAT and SPT) and load (light and heavy) showed significant group and load effects, but no main effect of task. The MS group performed worse than the controls and both groups performed better on the light load than the heavy load. Post hoc analysis indicated that performance on the PASAT 3 second trial was worse than on the PASAT 2 second trail compared to controls. Given that the PASAT 3 trial is theoretically easier than the PASAT 2 trial and that the PASAT 3 was administered first, the above results likely reflect learning effects. A Repeated Measures ANCOVA encompassing EEG and cognitive data (PASAT and SPT) indicated group-level differences on task performance, and suggested that at rest mean peak alpha frequency (PAF) is associated with performance on the PASAT, but not the SPT. EEG coherence during cognitive tasks was reduced between short-range connections in the theta, alpha, and beta frequency bins and enhanced in a limited number of long-range, anterior to posterior connections in the theta frequency bin in the MS group compared to controls. Finally, the MS participants had significantly more symptoms of depression and anxiety compared to normal controls. A hierarchical multiple regression analysis suggested that cognitive functioning is deleteriously affected by depression and anxiety. Overall, the results of this study substantiate the feasibility of utilizing QEEG as a physiological indicator of cognitive and cortical dysfunction in MS and show the importance of recognizing depression and anxiety and their contributions to cognitive deficits in individuals with MS.