Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 83
Filtrar
Más filtros

Bases de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
J Intern Med ; 289(6): 771-791, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33258193

RESUMEN

The treatment of multiple sclerosis (MS), the most common chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS), continues to transform. In recent years, a number of novel and increasingly effective disease-modulatory therapies (DMTs) have been approved, including oral fumarates and selective sphingosine 1-phosphate modulators, as well as cell-depleting therapies such as cladribine, anti-CD20 and anti-CD52 monoclonals. Amongst DMTs in clinical development, inhibitors of Bruton's tyrosine kinase represent an entirely new emerging drug class in MS, with three different drugs entering phase III trials. However, important remaining fields of improvement comprise tracking of long-term benefit-risk with existing DMTs and exploration of novel treatment targets relating to brain inherent disease processes underlying the progressive neurodegenerative aspect of MS, which accumulating evidence suggests start already early in the disease process. The aim here is to review current therapeutic options in relation to an improved understanding of the immunopathogenesis of MS, also highlighting examples where controlled trials have not generated the desired results. An additional aim is to review emerging therapies undergoing clinical development, including agents that interfere with disease processes believed to be important for neurodegeneration or aiming to enhance reparative responses. Notably, early trials now have shown initial evidence of enhanced remyelination both with small molecule compounds and biologicals. Finally, accumulating evidence from clinical trials and post-marketing real-world patient populations, which underscore the importance of early high effective therapy whilst maintaining acceptable tolerability, is discussed.


Asunto(s)
Esclerosis Múltiple , Ensayos Clínicos como Asunto , Humanos , Inmunosupresores , Esclerosis Múltiple/tratamiento farmacológico
2.
Eur J Neurol ; 27(2): 297-307, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31454130

RESUMEN

BACKGROUND AND PURPOSE: The aim was to study the prevalence of epilepsy in a hospital-based systemic lupus erythematosus (SLE) cohort and to investigate the relationship between epilepsy and other manifestations of neuropsychiatric SLE (NPSLE). METHODS: The study population consisted of 440 SLE patients recruited from 1998 to 2012. An epilepsy-screening questionnaire was sent to all patients, where those screening positive were invited to a neurological examination with documentation of NPSLE symptoms according to the American College of Rheumatology nomenclature. Occurrences of autoantibodies (double stranded DNAantibody, antinuclear antibody, lupus anticoagulant, Sjögren's syndrome A, Sjögren's syndrome B) and the antiphospholipid syndrome (APS) were tabulated. RESULTS: Out of 440 patients, 14% were dead and 2.7% were lost to follow-up. The questionnaire was sent to 368 patients; 312 (85%) responded. Of these, 131 (42%) screened positive. Epilepsy was confirmed in 36 (11.5%), of whom 30 (83%) had focal onset. Ten (3.2%) patients had isolated or provoked seizures. Manifestations of NPSLE occurred in 50%. The rates of cerebrovascular disease and psychosis were elevated two- and three-fold in NPSLE patients with epilepsy versus NPSLE patients without epilepsy, respectively (P = 0.001 and P = 0.0006). APS was more common in patients with epilepsy compared to epilepsy-free SLE patients with or without NPSLE (P = 0.02). In 50% of patients with epilepsy, no other etiology than SLE was detected. CONCLUSIONS: A high prevalence of epilepsy in SLE patients is reported, with association to concurrent cerebrovascular disease, APS and psychosis. Our findings support the notion of a multifactorial background for epilepsy in SLE including both vascular disease and features consistent with autoimmunity.


Asunto(s)
Epilepsia , Lupus Eritematoso Sistémico , Epilepsia/epidemiología , Epilepsia/etiología , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , Prevalencia , Factores de Riesgo
3.
Mol Psychiatry ; 23(5): 1244-1250, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-28289277

RESUMEN

Schizophrenia is characterized by a multiplicity of symptoms arising from almost all domains of mental function. γ-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain and is increasingly recognized to have a significant role in the pathophysiology of the disorder. In the present study, cerebrospinal fluid (CSF) concentrations of GABA were analyzed in 41 first-episode psychosis (FEP) patients and 21 age- and sex-matched healthy volunteers by high-performance liquid chromatography. We found lower CSF GABA concentration in FEP patients compared with that in the healthy volunteers, a condition that was unrelated to antipsychotic and/or anxiolytic medication. Moreover, lower CSF GABA levels were associated with total and general score of Positive and Negative Syndrome Scale, illness severity and probably with a poor performance in a test of attention. This study offers clinical in vivo evidence for a potential role of GABA in early-stage schizophrenia.


Asunto(s)
Trastornos Psicóticos/líquido cefalorraquídeo , Esquizofrenia/líquido cefalorraquídeo , Ácido gamma-Aminobutírico/líquido cefalorraquídeo , Adulto , Antipsicóticos/uso terapéutico , Encéfalo/metabolismo , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión/métodos , Femenino , Humanos , Masculino , Trastornos Psicóticos/diagnóstico , Esquizofrenia/tratamiento farmacológico , Adulto Joven
4.
Eur J Neurol ; 26(8): 1060-1067, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30762259

RESUMEN

BACKGROUND AND PURPOSE: Breakthrough disease on first-line injectables in relapsing-remitting multiple sclerosis (RRMS) is a common clinical situation where comparative studies between different escalation therapies are lacking. The aim of this study was to compare the efficacy, safety and medication persistence of natalizumab (NTZ), rituximab (RTX) and fingolimod (FGL) as escalation therapy in RRMS. METHODS: Patients switching from interferon or glatiramer acetate to NTZ, RTX or FGL due to breakthrough disease were identified through the Swedish multiple sclerosis (MS) registry at four large MS centers in this retrospective observational study. Data were collected from the MS registry and medical charts. Hazard ratios (HRs) for relapses, adverse events and drug discontinuation with 95% confidence interval (CI) were calculated using multivariable confounder-adjusted Cox proportional hazard models. RESULTS: A total of 241 patients were included. The annualized relapse rates were 0.02 for NTZ, 0.03 for RTX and 0.07 for FGL. Compared with NTZ, the adjusted HR for relapse was 1.0 (95% CI, 0.2-5.6) for RTX and 3.4 (95% CI, 1.3-9.2) for FGL. The annualized drug discontinuation rates were 0.15, 0.01 and 0.15 for NTZ, RTX and FGL, respectively. The adjusted HR for drug discontinuation was 0.05 (95% CI, 0.01-0.38) for RTX and 1.0 (95% CI, 0.6-1.7) for FGL vs. NTZ. CONCLUSIONS: In patients with RRMS on interferon/glatiramer acetate with breakthrough disease, switching to NTZ or RTX was associated with less disease activity compared with FGL. RTX displayed superior medication persistence compared with both NTZ and FGL.


Asunto(s)
Clorhidrato de Fingolimod/uso terapéutico , Factores Inmunológicos/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/uso terapéutico , Rituximab/uso terapéutico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Suecia , Resultado del Tratamiento
5.
Acta Psychiatr Scand ; 138(5): 432-440, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30132802

RESUMEN

OBJECTIVE: Accumulating evidence implicates immune activation in the development of schizophrenia. Here, monocyte numbers, monocyte chemoattractant protein-1 (MCP-1) and chitinase-3-like protein 1 (YKL-40) were investigated in plasma and cerebrospinal fluid (CSF) in first-episode psychosis (FEP) patients. METHOD: CSF and blood were sampled from 42 first-episode psychosis (FEP) patients and 22 healthy controls. The levels of YKL-40 and MCP-1 were measured using electrochemiluminescence assay, and blood monocytes were counted using an XN-9000-hematology analyzer. RESULTS: We found higher plasma levels of MCP-1 and YKL-40 in FEP patients compared with healthy controls, a condition that was unrelated to antipsychotic and/or anxiolytic medication. This was combined with an increased number of blood monocytes and a borderline significant increase in YKL-40 levels in the CSF of tobacco-free FEP patients. Plasma or CSF chemokines or blood monocytes did not correlate with the severity of symptoms or the level of functioning. CONCLUSION: These data demonstrate activation of monocytes in FEP and strengthens the idea of an immune dysfunction of psychotic disorders. Further studies are required to perceive a role of YKL-40 and MCP-1 in the initiation and progression of schizophrenia.


Asunto(s)
Quimiocina CCL2/sangre , Proteína 1 Similar a Quitinasa-3/sangre , Monocitos , Trastornos Psicóticos/sangre , Esquizofrenia/sangre , Adulto , Quimiocina CCL2/líquido cefalorraquídeo , Proteína 1 Similar a Quitinasa-3/líquido cefalorraquídeo , Femenino , Humanos , Recuento de Leucocitos , Masculino , Trastornos Psicóticos/líquido cefalorraquídeo , Trastornos Psicóticos/inmunología , Esquizofrenia/líquido cefalorraquídeo , Esquizofrenia/inmunología , Adulto Joven
6.
Acta Neurol Scand ; 136(5): 427-433, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28244170

RESUMEN

OBJECTIVE: To validate the diagnosis of idiopathic intracranial hypertension (IIH) from the Swedish National Patient Register (NPR) and investigate the incidence of IIH, as well as co-morbidities and medication use in a large Swedish population-based sample. METHODS: We searched the NPR to find all patients ≥18 years old with the ICD-10 diagnosis code (G93.2) for IIH in Stockholm County from Jan 1, 2006, to Dec 31, 2013. All medical records were reviewed to validate the diagnosis and to collect additional information. RESULTS: We included 207 patients with an IIH diagnosis, of which 135 (65%) were correctly diagnosed when validated by charts review. Eighty-three patients had disease onset during the study period. This gave a yearly incidence of 0.65/100 000. Female-to-male ratio was 6.1:1. Females, mean age 31.0 (CI 28.8-33.1), were younger at time of diagnosis compared to males, mean age 42.9 (CI 36.4-49.5), P<.001. The most common co-morbidities were obesity (92%), hormonal conditions (21%) and recent infections preceding the diagnosis (21%). Prior treatment with tetracycline derivatives were seen in 9%. CONCLUSION: The incidence of IIH in Stockholm is in the lower range of previously reported rates, possibly due to a lower prevalence of obesity. A substantial proportion of patients (35%) did not fulfill diagnostic criteria. Disease onset occurs at younger age in females. Co-morbidities were mainly associated with diseases affecting hormonal balance or causing inflammatory activation. These findings raise new hypothetical theories regarding mechanisms involved in IIH pathogenesis.


Asunto(s)
Obesidad/epidemiología , Seudotumor Cerebral/epidemiología , Adulto , Comorbilidad , Femenino , Humanos , Incidencia , Masculino , Registros Médicos , Persona de Mediana Edad , Prevalencia , Suecia/epidemiología
7.
Acta Neurol Scand ; 135(1): 17-24, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27558404

RESUMEN

Multiple sclerosis (MS) is associated with inflammatory lesions in the brain and spinal cord. The detection of such inflammatory lesions using magnetic resonance imaging (MRI) is important in the consideration of the diagnosis and differential diagnoses of MS, as well as in the monitoring of disease activity and predicting treatment efficacy. Although there is strong evidence supporting the use of MRI for both the diagnosis and monitoring of disease activity, there is a lack of evidence regarding which MRI protocols to use, the frequency of examinations, and in what clinical situations to consider MRI examination. A national workshop to discuss these issues was held in Stockholm, Sweden, in August 2015, which resulted in a Swedish consensus statement regarding the use of MRI in the care of individuals with MS. The aim of this consensus statement is to provide practical advice for the use of MRI in this setting. The recommendations are based on a review of relevant literature and the clinical experience of workshop attendees. It is our hope that these recommendations will benefit individuals with MS and guide healthcare professionals responsible for their care.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico por imagen , Guías de Práctica Clínica como Asunto , Humanos , Imagen por Resonancia Magnética/normas , Neurología/organización & administración , Sociedades Médicas , Suecia
9.
Scand J Immunol ; 84(5): 262-271, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27607184

RESUMEN

Tryptophan degradation along the kynurenine pathway is of central importance for the immune function. Toll-like receptors (TLRs), representing the first line of immune defence against pathogens, are expressed in various cell types. The most abundant expression is found on monocytes, macrophages and dendritic cells. The aim of this study was to investigate whether stimulation with different TLR ligands induces the kynurenine pathway in human peripheral monocytes. Cell supernatants were analysed using a liquid chromatography/mass spectrometry to measure kynurenine, kynurenic acid (KYNA), quinolinic acid (QUIN) and tryptophan. Stimulation of TLR-2, TLR-3, TLR-4, TLR-7/8 and TLR-9 was found to induce the production of kynurenine, but only stimulation of TLR-3 increased levels of further downstream metabolites, such as KYNA and QUIN. Stimulation of TLR-1, TLR-5 and TLR-6 did not induce the kynurenine pathway. Taken together, this study provides novel evidence demonstrating that TLR activation induces a pattern of downstream tryptophan degradation along the kynurenine pathway in monocytes. The results of this study may implicate that TLRs can be used as new drug targets for the regulation of aberrant tryptophan metabolism along this pathway, a potential therapeutic strategy that may be of importance in several disorders.


Asunto(s)
Quinurenina/inmunología , Monocitos/inmunología , Receptores Toll-Like/inmunología , Triptófano/inmunología , Flagelina/farmacología , Regulación de la Expresión Génica , Humanos , Hidrólisis , Imidazoles/farmacología , Ácido Quinurénico/inmunología , Ácido Quinurénico/metabolismo , Quinurenina/agonistas , Quinurenina/metabolismo , Lipopéptidos/farmacología , Lipopolisacáridos/farmacología , Listeria monocytogenes/química , Monocitos/citología , Monocitos/efectos de los fármacos , Poli I-C/farmacología , Cultivo Primario de Células , Isoformas de Proteínas/agonistas , Isoformas de Proteínas/genética , Isoformas de Proteínas/inmunología , Ácido Quinolínico/inmunología , Ácido Quinolínico/metabolismo , Transducción de Señal , Receptores Toll-Like/agonistas , Receptores Toll-Like/genética , Triptófano/metabolismo
10.
Mult Scler ; 22(1): 85-93, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25921036

RESUMEN

BACKGROUND: Natalizumab (NTZ) and fingolimod (FGL) are mainly used second line in relapsing-remitting multiple sclerosis (MS), although pivotal trials included mainly treatment-naïve patients. OBJECTIVE: This study aims to provide real-world data on safety and discontinuation rates. METHODS: Using IMSE, a drug monitoring registry for all newer MS drugs in Sweden, we analysed differences in baseline characteristics and 1-year drug survival for patients registered 2011-2013, initiating treatment with NTZ (n=640) or FGL (n=876). Among FGL initiators, n=383 (44%) had previously used NTZ (FGL(afterNTZ)). RESULTS: Compared with NTZ, the FGL cohort was older and more often male (36/38 years, 24%/33% males). Baseline Expanded Disability Status Scale was similar across groups, but MS Severity Score was higher in NTZ patients, and Symbol Digit Modalities Test and MS Impact Scale (MSIS-29) was higher in FGL(afterNTZ) versus FGL(NTZ-naïve) patients. Proportion on drug after 1 year was high, NTZ=87%, FGL(NTZ-naïve)=83% and FGL(afterNTZ)=76%. Adverse events was the most frequent reason for discontinuing FGL (FGL(NTZ-naïve)=9%, FGL(afterNTZ)=12%), and was significantly higher than on NTZ (3%). In contrast, the proportion of patients stopping treatment due to lack of effect was more similar: NTZ=4%, FGL(NTZ-naïve)=3%, FGL(afterNTZ)=8%. CONCLUSION: FGL and NTZ were both well tolerated, but FGL less so than NTZ, especially in patients switching to FGL from NTZ. Group differences were not explained by differences in recorded baseline characteristics.


Asunto(s)
Clorhidrato de Fingolimod/uso terapéutico , Factores Inmunológicos/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Natalizumab/uso terapéutico , Sistema de Registros , Adulto , Femenino , Clorhidrato de Fingolimod/efectos adversos , Humanos , Factores Inmunológicos/efectos adversos , Masculino , Persona de Mediana Edad , Natalizumab/efectos adversos , Índice de Severidad de la Enfermedad , Factores Sexuales , Suecia , Factores de Tiempo , Resultado del Tratamiento
11.
Acta Neurol Scand ; 134 Suppl 200: 47-54, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27580906

RESUMEN

Multiple sclerosis (MS) is a neuroinflammatory condition with a prominent progressive neurodegenerative facet that typically affects young- or middle-aged adults. Although physical disabilities have been in the foreground by being easier to assess, there is an increasing interest in mental disabilities and psychiatric co-morbidities, which have a disproportionally high impact on important outcome measures such as quality of life and occupational disability. In particular, cognitive impairment, depression and mental fatigue, which mutually interact with each other, seem to be of importance in this context. In recent decades, major efforts have been invested in developing more effective disease modulatory treatments. This has resulted in novel therapeutic options and awareness of the importance of early intervention. In comparison, good quality and adequately powered studies on symptomatic treatments of fatigue and psychiatric co-morbidities in MS are rare, and awareness of treatment options is much lower. We here review the existing evidence base for symptomatic treatment of fatigue and depression in MS patients. With regard to fatigue, off-label prescription of alertness improving drugs is common, in spite of all but absent evidence of efficacy. In contrast, a number of smaller studies suggest that physical exercise and fatigue management courses may have some clinical benefit. Very few studies have addressed the efficacy of antidepressants and non-pharmaceutical interventions specifically in MS patients. Therefore, treatment guidelines largely rely on data from non-MS populations. In the future, there is a strong motive to direct additional resources to the study of these important aspects of MS.


Asunto(s)
Depresión/terapia , Fatiga/terapia , Esclerosis Múltiple/complicaciones , Depresión/tratamiento farmacológico , Depresión/etiología , Fatiga/tratamiento farmacológico , Fatiga/etiología , Humanos
12.
J Intern Med ; 277(5): 594-604, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25251578

RESUMEN

OBJECTIVES: To determine the prevalence of myasthenia gravis (MG) and the rate of concurrent autoimmune diseases in patients with MG. DESIGN AND SETTING: Using the Swedish health and population registers, during the period 2005-2010, we conducted a nested case-control study of patients with MG (n = 2045) with five age- and sex-matched population-based controls per case. Register-based MG diagnosis was validated against the Stockholm MG Cohort. Similar nested case-control studies were conducted in patients with multiple sclerosis (MS), as a neuroinflammatory disease control, and siblings of patients with MG. MAIN OUTCOME MEASURE: Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated as a measure of the association between MG and other autoimmune diseases. RESULTS: The prevalence of MG was 24.8/100,000, and patients with MG had an increased risk of another autoimmune disease compared to controls (22.0% vs. 8.9%; OR: 2.82, 95% CI: 2.49-3.20); this risk was stronger amongst younger persons and women. Polymyositis/dermatomyositis, systemic lupus erythematosus and Addison's disease, three conditions regulated by the HLA-B8-DR3 haplotype, were most strongly associated with MG, especially early-onset disease. HLA typing in the Stockholm MG Cohort showed that early-onset MG was indeed dominated by HLA-B8-DR3. The risk of another autoimmune disease was increased in both patients with MS and siblings of patients with MG, compared to their respective controls, but to a lesser extent than in patients with MG. CONCLUSIONS: Our results suggest that MG shares risk factors with other autoimmune diseases, to a greater degree than MS, with a particular role of the HLA-B8-DR3 haplotype, especially amongst younger and female patients.


Asunto(s)
Enfermedades Autoinmunes/epidemiología , Adulto , Distribución por Edad , Anciano , Enfermedades Autoinmunes/complicaciones , Estudios de Casos y Controles , Femenino , Antígeno HLA-B8/genética , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Miastenia Gravis/complicaciones , Miastenia Gravis/epidemiología , Fenotipo , Prevalencia , Factores de Riesgo , Distribución por Sexo , Suecia/epidemiología
13.
Mult Scler ; 21(8): 1013-24, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25680984

RESUMEN

BACKGROUND AND OBJECTIVE: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. METHODS: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. RESULTS: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. CONCLUSIONS: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.


Asunto(s)
Esclerosis Múltiple/patología , Adulto , Estudios de Cohortes , Progresión de la Enfermedad , Endonucleasas , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina G/análisis , Imagen por Resonancia Magnética , Masculino , Esclerosis Múltiple/líquido cefalorraquídeo , Proteínas Nucleares/análisis , Bandas Oligoclonales/genética , Valor Predictivo de las Pruebas , Pronóstico , Medición de Riesgo , Análisis de Supervivencia , Vitamina D/sangre
14.
Genes Immun ; 15(3): 162-7, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24430172

RESUMEN

The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.


Asunto(s)
Epistasis Genética , Variación Genética , Antígenos HLA/genética , Esclerosis Múltiple/genética , Proteínas Nucleares/genética , Transactivadores/genética , Alelos , Estudios de Casos y Controles , Frecuencia de los Genes , Genotipo , Antígenos HLA/inmunología , Humanos , Desequilibrio de Ligamiento , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/inmunología , Oportunidad Relativa , Polimorfismo de Nucleótido Simple
15.
J Intern Med ; 275(4): 364-81, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24444084

RESUMEN

Multiple sclerosis (MS) is primarily an autoimmune disease of the central nervous system, but also encompasses prominent neurodegenerative aspects. A significant proportion of MS patients will develop neurological disability over time and up until recently treatment options have been limited. However, MS treatment is now at a stage of rapid progress, with several new drugs that have reached the market or will be launched in the near future. This provides new opportunities for individualized treatment, but also creates new challenges regarding monitoring of disease activity, long-term safety issues and efficacy, not least in patients with progressive disease.


Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Ensayos Clínicos como Asunto , Medicina Basada en la Evidencia , Humanos , Factores Inmunológicos/uso terapéutico , Inmunosupresores/administración & dosificación , Monitoreo Fisiológico , Resultado del Tratamiento
16.
Mult Scler ; 19(7): 863-70, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23175382

RESUMEN

BACKGROUND: The mechanisms of multiple sclerosis (MS) pathogenesis are still largely unknown. The heterogeneity of disease manifestations make the prediction of prognosis and choice of appropriate treatment protocols challenging. Recently, increased cerebrospinal fluid (CSF) levels of the B-cell chemokine CXCL13 was proposed as a possible marker for a more severe disease course and conversion from clinically isolated syndrome (CIS) to relapsing-remitting MS (RRMS). OBJECTIVE: To investigate whether there are genetic susceptibility variants in MS that correlate with the levels of CXCL13 present in the CSF of MS patients. METHODS: We genotyped the human leukocyte antigens HLA-DRB1 and HLA-A, plus a panel of single nucleotide polymorphisms (SNPs) that have been associated with susceptibility to MS and then correlated the genotypes with the levels of CXCL13, as measured with ELISA in the CSF of a total of 663 patients with MS, CIS, other neurological diseases (OND) or OND with an inflammatory component (iOND). RESULTS: Presence of the HLA-DRB1*15 and the MS risk genotypes for SNPs in the RGS1, IRF5 and OLIG3/TNFAIP3 gene regions correlated significantly with increased levels of CXCL13. CONCLUSION: Our results pointed towards a genetic predisposition for increased CXCL13 levels, which in MS patients correlates with the severity of the disease course. These findings encourage further investigation and replication, in an independent patient cohort.


Asunto(s)
Quimiocina CXCL13/líquido cefalorraquídeo , Predisposición Genética a la Enfermedad/genética , Esclerosis Múltiple/líquido cefalorraquídeo , Esclerosis Múltiple/genética , Biomarcadores/líquido cefalorraquídeo , Ensayo de Inmunoadsorción Enzimática , Genotipo , Antígenos HLA-A/genética , Cadenas HLA-DRB1/genética , Humanos , Polimorfismo de Nucleótido Simple , Pronóstico , Factores de Riesgo , Transcriptoma
17.
Mult Scler ; 19(6): 765-74, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23124789

RESUMEN

BACKGROUND: It is currently unknown whether early immunomodulatory treatment in relapsing-remitting MS (RRMS) can delay the transition to secondary progression (SP). OBJECTIVE: To compare the time interval from onset to SP in patients with RRMS between a contemporary cohort, treated with first generation disease modifying drugs (DMDs), and a historical control cohort. METHODS: We included a cohort of contemporary RRMS patients treated with DMDs, obtained from the Swedish National MS Registry (disease onset between 1995-2004, n = 730) and a historical population-based incidence cohort (onset 1950-64, n = 186). We retrospectively analyzed the difference in time to SP, termed the "period effect" within a 12-year survival analysis, using Kaplan-Meier and Cox regression analysis. RESULTS: We found that the "period" affected the entire severity spectrum. After adjusting for onset features, which were weaker in the contemporary material, as well as the therapy initiation time, the DMD-treated patients still exhibited a longer time to SP than the controls (hazard ratios: men, 0.32; women, 0.53). CONCLUSION: Our results showed there was a longer time to SP in the contemporary subjects given DMD. Our analyses suggested that this effect was not solely driven by the inclusion of benign cases, and it was at least partly due to the long-term immunomodulating therapy given.


Asunto(s)
Factores Inmunológicos/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Adulto , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/inmunología , Esclerosis Múltiple Recurrente-Remitente/mortalidad , Modelos de Riesgos Proporcionales , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Suecia/epidemiología , Factores de Tiempo , Resultado del Tratamiento
18.
Pilot Feasibility Stud ; 9(1): 41, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36922859

RESUMEN

BACKGROUND: Balance training interventions with a gradual progression of difficulty and highly challenging tasks designed specifically for people with multiple sclerosis (MS) are rare. The objective was to adapt a balance training intervention originally developed for Parkinson's disease through a co-design process and then conduct a pilot trial in MS to evaluate the feasibility of a large, full-scale study. METHODS: Twelve people with MS with mild to moderate overall MS-disability were included in this single-group feasibility trial. Participants received one-hour training sessions twice or three times weekly for 10 weeks. The assessment included tests of physical and cognitive functioning and patient-reported quality of life-related outcomes. Data on feasibility aspects were collected at baseline and follow-up assessments and three times during the intervention period to inform the recruitment process, as well as to monitor retention and inclusion rates, study procedures, intervention delivery, and dynamic changes in the selected potential outcome measures. Progression criteria were used to determine whether to proceed to a full-scale trial. Descriptive statistics were used to present the data. RESULTS: Out of six progression criteria, only retention and attendance at training sessions were not met. Reasons reported for not completing the intervention period mainly depended on external circumstances beyond the control of the study. In contrast, study procedures, intervention delivery, and intervention content (progression, adjustment, and control of challenge level of exercises) were considered feasible for a future, full-scale trial. The Mini-BESTest, which was used for the assessment of balance control, was considered suitable as the primary outcome in a full-scale trial with no ceiling or floor effects. Further, the Mini-BESTest showed a positive trend in outcome response with a median difference of 3.5 points between baseline and follow-up assessments. The power calculation performed suggests a feasible number of participants for recruitment. CONCLUSIONS: Overall trial aspects and intervention delivery were deemed feasible for a full-scale trial, but adjustments are needed to increase retention and attendance.

19.
Genes Immun ; 13(8): 632-40, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23052709

RESUMEN

The major histocompatibility complex class II transactivator (CIITA) gene (16p13) has been reported to associate with susceptibility to multiple sclerosis, rheumatoid arthritis and myocardial infarction, recently also to celiac disease at genome-wide level. However, attempts to replicate association have been inconclusive. Previously, we have observed linkage to the CIITA region in Scandinavian type 1 diabetes (T1D) families. Here we analyze five Swedish T1D cohorts and a combined control material from previous studies of CIITA. We investigate how the genotype distribution within the CIITA gene varies depending on age, and the association to T1D. Unexpectedly, we find a significant difference in the genotype distribution for markers in CIITA (rs11074932, P=4 × 10(-5) and rs3087456, P=0.05) with respect to age, in the collected control material. This observation is replicated in an independent cohort material of about 2000 individuals (P=0.006, P=0.007). We also detect association to T1D for both markers, rs11074932 (P=0.004) and rs3087456 (P=0.001), after adjusting for age at sampling. The association remains independent of the adjacent T1D risk gene CLEC16A. Our results indicate an age-dependent variation in CIITA allele frequencies, a finding of relevance for the contrasting outcomes of previously published association studies.


Asunto(s)
Diabetes Mellitus Tipo 1/genética , Predisposición Genética a la Enfermedad , Proteínas Nucleares/genética , Polimorfismo de Nucleótido Simple , Transactivadores/genética , Población Blanca , Adolescente , Adulto , Factores de Edad , Alelos , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Frecuencia de los Genes , Humanos , Lactante , Recién Nacido , Lectinas Tipo C/genética , Desequilibrio de Ligamiento , Masculino , Proteínas de Transporte de Monosacáridos/genética , Suecia
20.
Mult Scler Relat Disord ; 68: 104106, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36037752

RESUMEN

BACKGROUND: Exercise studies including only fatigued persons with multiple sclerosis (PwMS) with fatigue as primary endpoint are lacking. OBJECTIVE: To evaluate the effects of high-intensity resistance training (HIRT) on self-reported fatigue in fatigued PwMS in a single center randomised controlled trial. METHODS: We recruited 71 PwMS scoring ≥ 53 on the Fatigue Scale for Motor and Cognitive Functions (FSMC), who were randomised 1:1 to either twice (group A) or once (group B) weekly supervised HIRT for twelve weeks. A non-randomised FSMC score-matched group (n=69) served as non-intervention control. RESULTS: Between HIRT-group differences were non-significant for primary and most secondary endpoints. Mean difference in FSMC score (95% confidence intervals) was -10.9 (-14.8; -6.9) in group A and -9.8 (-13.2; -6.3) in group B. Corresponding values for combined HIRT groups vs non-intervention control were -10.3 (-12.9; -7.7) and 1.5 (-0.6;3.6), respectively, p<0.001. Secondary endpoints also improved in both HIRT groups, though only Hospital Anxiety and Depression Scale anxiety and MS Impact Scale-29 psychological subscales significantly favoured the twice a week HIRT (group A). As an exploratory endpoint, changes in plasma inflammatory protein markers were associated with reduced FSMC scores in the pooled material. CONCLUSION: The finding that HIRT in fatigued PwMS leads to clinically relevant reductions in self-reported fatigue, associated with changes in plasma inflammatory protein levels, provide evidence for recommending HIRT for fatigued PwMS.


Asunto(s)
Terapia Cognitivo-Conductual , Esclerosis Múltiple , Entrenamiento de Fuerza , Humanos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/terapia , Terapia por Ejercicio , Fatiga/terapia , Fatiga/complicaciones , Calidad de Vida
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA