RESUMO
BACKGROUND AND PURPOSE: Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti-inflammatory agents have failed to show efficacy in ameliorating disability progression. The aim of this study was to investigate a potential effect of anti-inflammatory disease-modifying treatment on disability outcomes in PPMS. METHODS: Using MSBase, a large, international, observational database, we identified patients with PPMS who were either never treated or treated with a disease-modifying agent. Propensity score matching was used to select subpopulations with similar baseline characteristics. Expanded Disability Status Scale (EDSS) outcomes were compared with an intention-to-treat and an as-treated approach in paired, pairwise-censored analyses. RESULTS: Of the 1284 included patients, 533 were matched (treated, n = 195; untreated n = 338). Median on-study pairwise-censored follow-up was 3.4 years (quartiles 1.2-5.5). No difference in the hazard of experiencing 3-month confirmed EDSS progression events was observed between the groups [hazard ratio (HR), 1.0; 95% confidence interval (CI), 0.6-1.7, P = 0.87]. We did not find significant differences in the hazards of confirmed EDSS improvement (HR, 1.0; 95% CI, 0.6-1.6, P = 0.91) or reaching a confirmed EDSS step ≥7 (HR, 1.1; 95% CI, 0.7-1.6, P = 0.69). CONCLUSION: Our pooled analysis of disease-modifying agents suggests that these therapies have no substantial effect on short- to medium-term disability outcomes in PPMS.
Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Adulto , Estudos de Coortes , Avaliação da Deficiência , Pessoas com Deficiência , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/patologiaRESUMO
BACKGROUND: The aim of this study was to examine whether work capabilities differ between workers with Multiple Sclerosis (MS) and workers from the general population. The second aim was to investigate whether the capability set was related to work and health outcomes. METHODS: A total of 163 workers with MS from the MS@Work study and 163 workers from the general population were matched for gender, age, educational level and working hours. All participants completed online questionnaires on demographics, health and work functioning. The Capability Set for Work Questionnaire was used to explore whether a set of seven work values is considered valuable (A), is enabled in the work context (B), and can be achieved by the individual (C). When all three criteria are met a work value can be considered part of the individual's 'capability set'. RESULTS: Group differences and relationships with work and health outcomes were examined. Despite lower physical work functioning (U = 4250, p = 0.001), lower work ability (U = 10591, p = 0.006) and worse self-reported health (U = 9091, p ≤ 0.001) workers with MS had a larger capability set (U = 9649, p ≤ 0.001) than the general population. In workers with MS, a larger capability set was associated with better flexible work functioning (r = 0.30), work ability (r = 0.25), self-rated health (r = 0.25); and with less absenteeism (r = - 0.26), presenteeism (r = - 0.31), cognitive/neuropsychiatric impairment (r = - 0.35), depression (r = - 0.43), anxiety (r = - 0.31) and fatigue (r = - 0.34). CONCLUSIONS: Workers with MS have a larger capability set than workers from the general population. In workers with MS a larger capability set was associated with better work and health outcomes. TRIAL REGISTRATION: This observational study is registered under NL43098.008.12: 'Voorspellers van arbeidsparticipatie bij mensen met relapsing-remitting Multiple Sclerose'. The study is registered at the Dutch CCMO register ( https://www.toetsingonline.nl ). This study is approved by the METC Brabant, 12 February 2014. First participants are enrolled 1st of March 2014.
Assuntos
Ansiedade/etiologia , Depressão/etiologia , Emprego/estatística & dados numéricos , Esclerose Múltipla/complicações , Avaliação de Resultados em Cuidados de Saúde/normas , Avaliação da Capacidade de Trabalho , Absenteísmo , Adulto , Estudos de Casos e Controles , Estudos Transversais , Emprego/psicologia , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/psicologia , Qualidade de Vida , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Early prediction of long-term disease evolution is a major challenge in the management of multiple sclerosis (MS). Our aim was to predict the natural course of MS using the Bayesian Risk Estimate for MS at Onset (BREMSO), which gives an individual risk score calculated from demographic and clinical variables collected at disease onset. METHODS: An observational study was carried out collecting data from MS patients included in MSBase, an international registry. Disease impact was studied using the Multiple Sclerosis Severity Score (MSSS) and time to secondary progression (SP). To evaluate the natural history of the disease, patients were analysed only if they did not receive immune therapies or only up to the time of starting these therapies. RESULTS: Data from 14 211 patients were analysed. The median BREMSO score was significantly higher in the subgroups of patients whose disease had a major clinical impact (MSSS≥ third quartile vs. ≤ first quartile, P < 0.00001) and who reached SP (P < 0.00001). The BREMSO showed good specificity (79%) as a tool for predicting the clinical impact of MS. CONCLUSIONS: BREMSO is a simple tool which can be used in the early stages of MS to predict its evolution, supporting therapeutic decisions in an observational setting.
Assuntos
Progressão da Doença , Esclerose Múltipla/diagnóstico , Sistema de Registros , Índice de Gravidade de Doença , Adulto , Feminino , Humanos , Masculino , Prognóstico , RiscoRESUMO
OBJECTIVE: Insufficient sun exposure and vitamin D deficiency have both been associated with increased risk of multiple sclerosis (MS). Depressi on, anxiety, fatigue and cognitive impairment are prevalent and disabling symptoms in MS. Our objective was to examine the associations between personal sun exposure and serum 25-hydroxyvitamin D (25(OH)D), and depression, anxiety, fatigue and cognition. METHODS: A total of 198 participants with multiple sclerosis were followed prospectively for an average of 2.3 years. Assessments of serum 25(OH)D, sun exposure, depression, anxiety and fatigue were carried out biannually; cognition was assessed annually. RESULTS: Personal reported sun exposure was inversely associated with depression scores (ß -0.26 (95%CI -0.40, -0.12);P ≤ 0.001) and fatigue scores (ß -0.65 (95%CI -1.23, -0.07); P = 0.028). Only high levels of 25(OH)D (>80 nm) were inversely associated depression scores (ß -0.64 (95%CI -1.15, -0.13); P = 0.015), but this was not significant after adjustment for reported sun exposure. No associations were seen between reported sun exposure or serum 25(OH)D levels and anxiety or cognition scores. CONCLUSION: We found that higher levels reported sun exposure, rather than 25(OH)D levels, were associated with less depressive symptoms and levels of fatigue. The role of UV or light therapy will need to be evaluated in randomized controlled trials to confirm an effect on these symptoms in MS.
Assuntos
Depressão , Fadiga , Esclerose Múltipla/psicologia , Luz Solar , Vitamina D/sangue , Adulto , Idoso , Ansiedade/sangue , Cognição , Depressão/sangue , Fadiga/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Estudos Prospectivos , Adulto JovemRESUMO
Multiple sclerosis immunomodulatory treatments such as cladribine, which affects both B- and T-lymphocytes, can potentially alter the humoral response to SARS-CoV-2 vaccination. This monocenter retrospective study reports on anti-SARS-CoV-2 IgG antibody response in cladribine treated MS patients and we compare the response in patients vaccinated before and after an 18-week interval after last cladribine dose. Of the 34 patients (5 patients ≤ 18 weeks and 29 patients > 18 weeks after last cladribine dose) that were included, 32 reached seropositivity (94 %). All patients vaccinated < 18 weeks after last cladribine dose reached seropositivity. This study confirms findings of earlier reports that cladribine-treated MS patients show an adequate humoral response after SARS-CoV-2 vaccination, even when vaccinated early (≤18 weeks) after last cladribine dose.
RESUMO
Vitamin D skews the immune system towards a more tolerogenic state. Therefore, a relatively high vitamin D status, i.e., within the normal physiological range, might result in a lower antibody response to infection and vaccination. We hypothesized, however, that vitamin D is primarily important in establishing immune homeostasis, implying that a relatively high vitamin D status would not hamper an adequate antibody response against pathogens. Our results show that the vitamin D status did not differ between responders and hypo-responders in patients infected with Streptococcus pneumoniae, as well as patients vaccinated against S. pneumoniae, Neisseria meningitidis type C (MenC), and/or Haemophilus influenzae type b (Hib). Furthermore, specific IgG titers were not associated with the vitamin D status in patients vaccinated against S. pneumoniae and MenC, while there was a weak inverse association in Hib-vaccinated patients. These data indicate that a relatively high vitamin D status does not seem to hamper an adequate antibody response upon infection or vaccination, suggesting that vitamin D, in this setting, is not immunosuppressive.
Assuntos
Anticorpos Antibacterianos/sangue , Formação de Anticorpos , Haemophilus influenzae/imunologia , Neisseria meningitidis/imunologia , Streptococcus pneumoniae/imunologia , Vitamina D/sangue , Adulto , Infecções Bacterianas/imunologia , Vacinas Bacterianas/imunologia , Estudos de Coortes , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Soro/imunologiaRESUMO
BACKGROUND: Patients with multiple sclerosis (MS) are more frequently born in spring when compared to autumn. Fluctuation of UV-light has been hypothesized to drive this phenomenon. AIM: To assess the correlation between fluctuation of sunlight and birth season in persons with MS. METHODS: For this record-linkage study, we collected from the international MSBase and the Italian MS iMed-web databases the dates of birth of 11,415 patients with MS from 36 centres from 15 countries worldwide and compared these to dates of live-births from national registries. From all participating sites, we collected data on UV-light fluctuation and assessed its correlation with seasonal fluctuation in MS births. RESULTS: Compared with the reference cohort, an increased proportion of persons with MS were born in spring and a decreased proportion in autumn (odds ratio (OR) to be born in spring versus autumn = 1.158, χ² = 36.347, P < 0.001). There was no significantly increased fluctuation of MS births with increased quartile of ambient UV-light fluctuation (Ptrend = 0.086). CONCLUSION: Seasonal fluctuation of MS births as found in this worldwide cohort of patients with MS did not correlate with variation in seasonal fluctuation of UV-light. Most likely, it results from a complex interplay between fluctuation of sunlight, behavioural factors, other environmental factors and (epi)genetic factors.
Assuntos
Esclerose Múltipla/epidemiologia , Efeitos Tardios da Exposição Pré-Natal , Estações do Ano , Luz Solar , Raios Ultravioleta , Bases de Dados Factuais , Feminino , Saúde Global , Humanos , Masculino , Gravidez , Sistema de Registros , Fatores de RiscoRESUMO
BACKGROUND: With the advent of MRI scanning, the value of lumbar puncture to assess oligoclonal band (OCB) status-for the diagnosis of multiple sclerosis (MS) is increasingly uncertain. One major issue is that the reported frequency of cerebrospinal fluid (CSF)-restricted oligoclonal banding for the diagnosis of MS varies considerably in different studies. In addition, the relationship between OCB positivity and disease outcome remains uncertain, as reported studies are generally too small to assess comparative disability outcomes with sufficient power. METHODS: In order to further investigate variation of OCB positivity in patients with MS, we utilized MSBase, a longitudinal, Web-based collaborative MS outcomes registry following clinical cohorts in several continents and latitudes. We also assessed whether OCB positivity affects long-term disability outcome. RESULTS: A total of 13,242 patient records were obtained from 37 MS specialist centres in 19 different countries. OCB status was documented in 4481 (34%) patients and 80% of these were OCB positive. The presence of OCB was associated with degree of latitude (p = 0.02). Furthermore, the outcome of patients negative for CSF-specific OCB was significantly better in comparison to the OCB positive patients, as assessed by Expanded Disability Status Scale change (p < 0.001). CONCLUSIONS: The results of this study indicate that latitude could explain some of the inconsistencies in OCB status reported in different populations. The study confirms that OCB positivity in MS is associated with a worse long-term prognosis.
Assuntos
Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/epidemiologia , Bandas Oligoclonais/líquido cefalorraquidiano , Adulto , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Sistema de RegistrosRESUMO
OBJECTIVES: Fatigue is one of the most common and troubling symptoms of multiple sclerosis (MS), and heat is often reported as a trigger. Although it is assumed that this heat sensitivity is specific for MS, the evidence for disease specificity is limited. We studied the relationship between fatigue, heat sensitivity, and environmental temperature, and its specificity for MS. MATERIALS AND METHODS: We compared 88 MS patients with 76 patients with ulcerative colitis (UC), another chronic auto-immune disease. As most important outcome measures, heat sensitivity, physical fatigue, mental fatigue, environmental temperature, and ambient UV-light levels were determined. RESULTS: More patients with MS reported heat sensitivity for fatigue, compared to patients with UC (53.4% vs 35.5%, respectively, P = 0.016). However, heat-sensitive patients were equally fatigued as heat-insensitive patients. Climatological data, including day temperature and amount of ambient UV light, were not related to fatigue in both heat-sensitive and heat-insensitive patients with MS. CONCLUSIONS: Our findings support the assumption that heat sensitivity regarding fatigue has an MS-specific component. Although patients with MS experience a relationship between environmental temperature and fatigue, objective assessment by climatological data could not confirm this.
Assuntos
Fadiga/etiologia , Temperatura Alta/efeitos adversos , Esclerose Múltipla/complicações , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Depressive symptoms and fatigue are frequent and disabling symptoms of multiple sclerosis (MS). Depression and fatigue have been associated with a poor vitamin D status, and a poor vitamin D status is often found in MS. AIM: Assess whether vitamin D status contributes to depressive symptoms and fatigue in MS. METHODS: Patients with MS that participated in previous studies in which depression and fatigue were assessed and of whom serum 25-hydroxyvitamin D (25(OH)D) levels were available within a timeframe of less than one half-life of 25(OH)D were included. Depression and fatigue were assessed with the Hospital Anxiety and Depression Scale and the Multidimensional Fatigue Inventory. RESULTS: Fifty-nine patients were included. Mean scores of fatigue and depression were 14.6 (SD 4.2) and 6.2 (SD 4.4), respectively. The mean vitamin D status was 62.3 nm (SD 27.8). Vitamin D status correlated negatively with depression (r=-0.326, P=0.006). No significant correlation was found between vitamin D status and fatigue. In a multiple regression model, vitamin D status was not a significant contributor to depression, after controlling for age Expanded Disability Status Scale score and fatigue (P=0.078). Alternatively, depression and fatigue did not contribute to vitamin D status. DISCUSSION: This study shows a negative correlation between vitamin D status and depressive symptoms in patients with MS. Although multiple confounders exist, we observed an indication that vitamin D status might contribute to the presence of depressive symptoms in MS. Therefore, further studies on vitamin D in MS should include depressive symptoms as outcome measures to confirm these findings.
Assuntos
Depressão/epidemiologia , Síndrome de Fadiga Crônica/epidemiologia , Esclerose Múltipla/epidemiologia , Deficiência de Vitamina D/epidemiologia , Adulto , Idoso , Comorbidade/tendências , Depressão/sangue , Depressão/diagnóstico , Síndrome de Fadiga Crônica/sangue , Síndrome de Fadiga Crônica/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla/psicologia , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Adulto JovemRESUMO
The effects of dimethyl fumarate (DMF) on the immune system in multiple sclerosis (MS) are not completely elucidated. In this study, an extensive immunophenotypic analysis of innate and adaptive immune cells of DMF-treated MS patients was performed. Peripheral blood immune cell phenotypes were determined using flow cytometry in a follow-up study of 12 MS patients before, after 3 and 12 months of DMF treatment and a cross-sectional study of 25 untreated and 64 DMF-treated MS patients. Direct effects of DMF on B cells were analyzed in vitro. After 12 months of DMF treatment, percentages of monocytes, natural killer cells, naive T and B cells and transitional B cells increased. Percentages of (effector) memory T cells, (non) class-switched memory B cells and double negative B cells decreased together with CD4+ T cells expressing interferon-γ (IFN-γ), granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-17 (IL-17). DMF treatment was fully effective as of 6 months and directly induced apoptosis and decreased expression of costimulatory CD40, antigen presentation molecule MHCII and B cell activating factor receptor (BAFFR) on B cells. DMF induced a persistent change of the immune system of MS patients, directly induced apoptosis and reduced expression of functional markers on B cells.
Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Fumarato de Dimetilo/uso terapêutico , Imunidade Inata/efeitos dos fármacos , Imunossupressores/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Adulto , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Adulto JovemRESUMO
We applied a cDNA phage display method called serological antigen selection (SAS) to identify immunogenic targets that evoke an autoantibody response in the serum of multiple sclerosis (MS) patients. This method involves the display of a cDNA expression library, in this study a MS brain library, on filamentous phage and subsequent selection using patient immunoglobulin G (IgG). To apply the SAS technology for autoantibodies in the serum of MS patients, an optimization was necessary to deplete cDNA products that encode IgG fragments derived from B cells present in the MS brain plaques. We describe a differential screening procedure in which positive selection rounds on MS serum and negative selection rounds on healthy control serum were alternated to optimize the selection procedure. As a result, a substantial decrease of IgG-displaying phage clones was observed after each negative selection round, thereby preventing an overgrowth of IgG-displaying phage clones. Our depletion strategy was therefore successful in preventing the enrichment of IgG-displaying phage clones. This approach will facilitate the identification of possible MS-related antigens.
Assuntos
Autoanticorpos/sangue , Autoanticorpos/genética , Perfilação da Expressão Gênica/métodos , Biblioteca Gênica , Esclerose Múltipla/sangue , Esclerose Múltipla/imunologia , Antígenos/sangue , Antígenos/imunologia , Autoanticorpos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transcrição Gênica/genéticaRESUMO
The NLRP3 inflammasome is a macromolecular complex importantly involved in IL-1ß processing. A role for this has been described in multiple sclerosis (MS). One mechanism by which IL-1ß might be involved in MS is by inducing pathogenic Th17 cells, i.e. GM-CSF+ Th17 cells. In the present study, we show that expression of the inflammasome related genes, NLRP3, caspase-1, IL-1ß and the IL-1ß/IL-1Ra ratio, was increased in PBMC from MS patients compared to healthy controls (HC). However, in an in vitro inflammasome activity assay with PBMC, IL-1ß protein secretion and the IL-1ß/IL-1Ra protein ratio were similar in MS patients and HC. Th cells cultured in the presence of supernatant derived from LPS/ATP inflammasome activated PBMC showed increased Th17 and GM-CSF+ Th17 cell frequencies in HC and MS patients and decreased anti-inflammatory IL-10+Th cell frequency in HC compared to Th cells cultured in the presence of control supernatant. Moreover, addition of the immune modulator calcitriol to the former condition resulted in reduced frequencies of Th17 and GM-CSF+Th17 cells, and also of IL-10+ Th cells. Evidently, our data indicate that inflammasome activity can skew the Th cell population toward a more pro-inflammatory composition, an effect that might be inhibited by vitamin D, and that might be importantly involved in inflammation within the central nervous system.
Assuntos
Perfilação da Expressão Gênica , Inflamassomos/genética , Leucócitos Mononucleares/metabolismo , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Células Th17/imunologia , Trifosfato de Adenosina/farmacologia , Adulto , Estudos de Casos e Controles , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Regulação para Baixo/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamassomos/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-1beta/sangue , Interleucina-1beta/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/metabolismo , Células Th17/efeitos dos fármacos , Células Th17/patologia , Vitamina D/farmacologia , Adulto JovemRESUMO
BACKGROUND/OBJECTIVE: Data from animal models of MS suggest that GM-CSF(+)CD4(+)T cells are pathogenic cells. Therefore, GM-CSF production by CD4(+)T cells of MS patients and their susceptibility to regulatory mechanisms were investigated. METHODS: Intracellular flowcytometry was performed to determine the GM-CSF(+)CD4(+)T cell fraction in PBMC and CSF of MS patients and controls. The effect of regulatory T cells (Tregs) on GM-CSF production by CD4(+)T cells was studied in MS patients using a proliferation-suppression assay. Finally, GM-CSF(+)CD4(+)T cell fraction and GM-CSF protein levels in supernatant were assessed in anti-CD3-stimulated CD4(+)T cell cultures derived from healthy controls and MS patients, in the presence or absence of the active vitamin D metabolite calcitriol. RESULTS: The GM-CSF(+)CD4(+)T cell fraction in the peripheral blood did not differ between controls and MS patients. This T cell population could also be detected in the CSF of both subjects with MS as well as subjects with another diagnosis. In the CSF, it comprised a significant fraction of the T cell population. Upon in vitro stimulation of PBMC with anti-CD3 antibody, no differences were observed in GM-CSF(+)CD4(+)T cell frequencies. GM-CSF secretion was susceptible to regulation by Treg and vitamin D. Suppression of GM-CSF secretion by vitamin D was reduced in MS patients. CONCLUSIONS: Our study showed no elevation in GM-CSF(+)CD4(+)T cell fractions in MS patients compared to controls. Furthermore, GM-CSF secretion was prone to regulation by Treg and vitamin D, the latter being less effective in MS patients.
Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Esclerose Múltipla/patologia , Linfócitos T Reguladores/fisiologia , Vitamina D/farmacologia , Adulto , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Although the exact etiology of MS remains elusive, there is good evidence that genetic factors play an important role. These factors are likely to be polygenic, exerting both independent and interactive effects on the expression of MS. They may determine susceptibility and/or shape the clinical course. METHODS: The authors studied clinical phenotype in 245 concordant parent-child pairs recruited from a national register of familial disease over a 10-year period. Data were examined in order to determine the effect of parental sex on expression of disease in the offspring. RESULTS: Allowing for the observed sex ratio of 2.6 F:1 M in this group of patients, sex pairings of parents and offspring were close to those expected. When assessed independently there was no evidence that either the sex of the affected offspring or the line of inheritance influenced disability, age at onset, or disease course. However, trends were observed toward greater disability and an increased frequency of primary progressive disease in offspring of affected fathers and an earlier age at onset in offspring of affected mothers. The highest mean Expanded Disability Status Scale score was observed in male offspring of affected fathers (5.64) and this group was also more likely to have primary progressive disease (OR 1.92). Thirty-one percent of families had an additionally affected offspring with no preferential maternal or paternal transmission. CONCLUSIONS: In offspring of concordant parent-child families with MS who are at high risk of inheriting increased numbers of susceptibility genes there is no evidence for a parent of origin effect distorting sex ratios in affected offspring, but parent of origin may influence disability and disease course as well as increasing the risk to additional offspring within the same family. The mechanism of these effects is not clear but may result from interactions between genes encoded at different loci (epistasis), which each independently influence susceptibility and phenotype.
Assuntos
Esclerose Múltipla/epidemiologia , Esclerose Múltipla/fisiopatologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Distribuição por SexoRESUMO
We studied the relationship between infarct size and degree of internal carotid artery stenosis in 227 stroke patients without a source of embolism in the heart, who had a CT-verified territorial brain infarct. We used logistic regression analysis adjusting for differences between groups in co-associated variables such as age, sex, hypertension, diabetes mellitus, and a history of ischaemic heart disease. Ipsilateral carotid stenosis greater than 50% was more strongly associated with large than small infarcts; adjusted odds ration [(a)OR]: 4.56; 95% confidence interval (CI): 1.21-17.2; P = 0.02. For ipsilateral carotid occlusion the association was even stronger--(a)OR: 36.80; 95% CI: 2.54-533; P = 0.007. When large infarcts were compared with infarcts of small and moderate size together the ORs were 2.29, 95% CI 1.14-4.58 and 2.57, 95% CI 1.17-5.67 for carotid stenosis or occlusion, respectively. Our data show a relationship between greater than 50% carotid stenosis or occlusion and large brain infarcts. We suggest that haemodynamic impairment may contribute to infarct size in territorial infarcts of non-cardiac origin.
Assuntos
Artérias Carótidas/diagnóstico por imagem , Infarto Cerebral/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
Borderzone infarcts are usually regarded as being caused by low cerebral blood flow distal to a severely stenosed or occluded artery, particularly the internal carotid artery. To explore this hypothesis we have related borderzone infarction, defined by CT both in the classical way and by taking into account the variable extent of the territory of the blood supply of the cerebral arteries, to the severity of any disease of the symptomatic artery in 384 patients in the European Carotid Surgery Trial in whom a scan showing infarction was available. Although there was a tendency for borderzone infarction to occur more often distal to severe carotid disease, this was not significant, and many cases of borderzone infarcts occurred in patients with mild or moderate carotid disease. Therefore, the topography of infarction on CT cannot be used to imply a particular pathophysiology based on the severity of disease of the artery supplying that area of the brain. Severe carotid stenosis is neither sufficient nor necessary to produce borderzone infarction. However, it has to be emphasized that patients with carotid occlusion are not included in this study.
Assuntos
Estenose das Carótidas/complicações , Infarto Cerebral/etiologia , Idoso , Artéria Carótida Interna/diagnóstico por imagem , Angiografia Cerebral , Infarto Cerebral/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Tomografia Computadorizada por Raios XRESUMO
A case of tuberculous brain abscess occurred in spite of 4 months' treatment of pulmonary tuberculosis with a triple drug anti-tuberculous regimen. Surgical removal and further chemotherapy were successful.
Assuntos
Abscesso Encefálico/cirurgia , Tuberculose/cirurgia , Abscesso Encefálico/diagnóstico por imagem , Abscesso Encefálico/tratamento farmacológico , Abscesso Encefálico/patologia , Etambutol/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Pirazinamida/uso terapêutico , Tomografia Computadorizada por Raios X , Tuberculose/diagnóstico por imagem , Tuberculose/tratamento farmacológico , Tuberculose/patologiaRESUMO
Two patients are presented with progressive invalidating uremic peripheral neuropathy. The peripheral neuropathy developed despite frequent hemodialysis with a polyacrylonitrile membrane and afterwards in combination with CAPD. The first patient with a long history of progressive peripheral neuropathy before renal transplantation recovered incompletely after renal transplantation, whereas the second patient with a short history of a severe progressive UPN recovered completely after renal transplantation.
Assuntos
Falência Renal Crônica/cirurgia , Transplante de Rim , Doenças do Sistema Nervoso Periférico/terapia , Uremia/terapia , Adulto , Humanos , Masculino , Doenças do Sistema Nervoso Periférico/etiologia , Diálise Peritoneal Ambulatorial Contínua , Uremia/complicaçõesRESUMO
OBJECTIVE: In 4% to 31% of patients with acute subarachnoid hemorrhage (SAH), no underlying cause is identified. Blood is restricted to the perimesencephalic cisterns in about two thirds of these patients. These patients are identified as having perimesencephalic nonaneurysmal subarachnoid hemorrhage (PNSAH), a syndrome based on the interpretation of computed tomography (CT) findings on admission, with an excellent prognosis, far better than other patients with SAH with or without an aneurysm. However, the diagnosis is subject to interrater variability, and differentiation between PNSAH and ruptured supratentorial aneurysm by means of CT has not been investigated. Therefore we investigated the validity of prediction of PNSAH with CT scan. METHODS: A total of 303 consecutive patients, admitted within 72 hours after the initial bleeding with symptoms and signs of spontaneous SAH, which was confirmed by CT or spectrophotometric analysis of the cerebrospinal fluid (CSF) in whom either a selective 4-vessel angiogram (n = 293) or postmortem examination (n = 10) was performed, were studied. RESULTS: We found an interrater agreement for the diagnosis perimesencephalic nonaneurysmal subarachnoid hemorrhage of 93% and a kappa value of 0.65. Sensitivity was 30% for observer 1 and 46% for observer 2. The positive predictive value was 73% for observer 1 and 76% for observer 2. Among those diagnosed as having PNSAH, we found vertebrobasilar artery aneurysms in 19% (both raters) and internal carotid artery aneurysms in 5% (observer 1) and 8% (observer 2). CONCLUSION: We conclude that PNSAH can be distinguished on CT in the majority of patients; however, the angiographical management in PNSAH should not differ from other SAHs.