ABSTRACT
INTRODUCTION: Natalizumab (NTZ) is a very effective treatment approved for highly active multiple sclerosis. The main risk of treatment with NTZ is the possibility of developing progressive multifocal leukoencephalopathy, which is related to JC virus positivity and the number of NTZ infusions. This risk decreases with the extended dosage interval (EDI), which involves 9 or fewer infusions/year. However, it is a matter of controversy as to whether EDI remains effective in reducing recurrences and the presence of new lesions in magnetic resonance imaging (MRI). PATIENTS AND METHODS: A prospective observational study was conducted from 1 April 2019 to 30 June 2021, following up patients on NTZ treatment who switched to EDI. Patients should have at least one MRI six months after the start of EDI. The presence of attacks or MRI activity (new lesions in T2) during the EDI was recorded. RESULTS: Twenty-three patients with a mean age of 43.5 ± 9.4 years were included. The median number of NTZ infusions was 68 (minimum, 25; maximum, 127). The median interval between the start of the EDI and the last MRI was 14 months (minimum, 6; maximum, 25), and 23 months from the last medical follow-up visit (minimum, 7; maximum, 28). Two patients (8.7%) presented with attacks and two others (8.7%) showed MRI activity. CONCLUSIONS: EDI with NTZ maintains high clinical and activity effectiveness in MRI.
TITLE: Efectividad clínica y radiológica del intervalo extendido de dosis con natalizumab en pacientes con esclerosis múltiple recurrente.Introducción. El natalizumab (NTZ) es un tratamiento de alta eficacia aprobado para la esclerosis múltiple de alta actividad. El principal riesgo del tratamiento con NTZ es la posibilidad de desarrollar una leucoencefalopatía multifocal progresiva, que está en relación con la positividad al virus JC y el número de infusiones del NTZ. Este riesgo disminuye con el intervalo extendido de dosis (IED), lo que supone 9 infusiones/año o menos. Sin embargo, es materia de controversia si el IED mantiene la efectividad sobre la reducción de las recurrencias y la presencia de nuevas lesiones en la resonancia magnética (RM). Pacientes y métodos. Se ha realizado un estudio observacional prospectivo desde el 1 de abril de 2019 hasta el 30 de junio de 2021, siguiendo a los pacientes en tratamiento con NTZ que se pasaron al IED. Los pacientes deberían tener al menos una RM a los seis meses del inicio del IED. Se registró la presencia de brotes o de actividad en la RM (nuevas lesiones en T2) durante el IED. Resultados. Se incluyó a 23 pacientes con una media de edad de 43,5 ± 9,4 años. La mediana de infusiones de NTZ fue de 68 (mínimo, 25; máximo, 127). La mediana del intervalo entre el inicio del IED y la última RM fue de 14 meses (mínimo, 6; máximo, 25), y de 23 meses respecto a la última visita de seguimiento médico (mínimo, 7; máximo, 28). Dos pacientes (8,7%) presentaron brotes y otros dos pacientes (8,7%) presentaron actividad en la RM. Conclusiones. El IED de NTZ mantiene una alta efectividad clínica y de actividad en la RM.
Subject(s)
Leukoencephalopathy, Progressive Multifocal , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Adult , Humans , Immunologic Factors/adverse effects , Immunologic Factors/therapeutic use , Leukoencephalopathy, Progressive Multifocal/chemically induced , Middle Aged , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Natalizumab/adverse effects , Natalizumab/therapeutic use , RecurrenceABSTRACT
Introducción: El natalizumab (NTZ) es un tratamiento de alta eficacia aprobado para la esclerosis múltiple de alta actividad. El principal riesgo del tratamiento con NTZ es la posibilidad de desarrollar una leucoencefalopatía multifocal progresiva, que está en relación con la positividad al virus JC y el número de infusiones del NTZ. Este riesgo disminuye con el intervalo extendido de dosis (IED), lo que supone 9 infusiones/año o menos. Sin embargo, es materia de controversia si el IED mantiene la efectividad sobre la reducción de las recurrencias y la presencia de nuevas lesiones en la resonancia magnética (RM). Pacientes y métodos: Se ha realizado un estudio observacional prospectivo desde el 1 de abril de 2019 hasta el 30 de junio de 2021, siguiendo a los pacientes en tratamiento con NTZ que se pasaron al IED. Los pacientes deberían tener al menos una RM a los seis meses del inicio del IED. Se registró la presencia de brotes o de actividad en la RM (nuevas lesiones en T2) durante el IED. Resultados: Se incluyó a 23 pacientes con una media de edad de 43,5 ± 9,4 años. La mediana de infusiones de NTZ fue de 68 (mínimo, 25; máximo, 127). La mediana del intervalo entre el inicio del IED y la última RM fue de 14 meses (mínimo, 6; máximo, 25), y de 23 meses respecto a la última visita de seguimiento médico (mínimo, 7; máximo, 28). Dos pacientes (8,7%) presentaron brotes y otros dos pacientes (8,7%) presentaron actividad en la RM. Conclusiones: El IED de NTZ mantiene una alta efectividad clínica y de actividad en la RM.(AU)
Introduction: Natalizumab (NTZ) is a very effective treatment approved for highly active multiple sclerosis. The main risk of treatment with NTZ is the possibility of developing progressive multifocal leukoencephalopathy, which is related to JC virus positivity and the number of NTZ infusions. This risk decreases with the extended dosage interval (EDI), which involves 9 or fewer infusions/year. However, it is a matter of controversy as to whether EDI remains effective in reducing recurrences and the presence of new lesions in magnetic resonance imaging (MRI). Patients and methods: A prospective observational study was conducted from 1 April 2019 to 30 June 2021, following up patients on NTZ treatment who switched to EDI. Patients should have at least one MRI six months after the start of EDI. The presence of attacks or MRI activity (new lesions in T2) during the EDI was recorded. Results: Twenty-three patients with a mean age of 43.5 ± 9.4 years were included. The median number of NTZ infusions was 68 (minimum, 25; maximum, 127). The median interval between the start of the EDI and the last MRI was 14 months (minimum, 6; maximum, 25), and 23 months from the last medical follow-up visit (minimum, 7; maximum, 28). Two patients (8.7%) presented with attacks and two others (8.7%) showed MRI activity. Conclusions: EDI with NTZ maintains high clinical and activity effectiveness in MRI.(AU)
Subject(s)
Humans , Male , Female , Middle Aged , Natalizumab/administration & dosage , Multiple Sclerosis/complications , Multiple Sclerosis/drug therapy , Risk Management , Leukoencephalopathy, Progressive Multifocal , JC Virus , Prospective Studies , Neurology , Nervous System DiseasesABSTRACT
No disponible
Subject(s)
Humans , Female , Aged , Carbamazepine , Anticonvulsants , Pancreatitis , Pancreatitis , Liver Function TestsABSTRACT
INTRODUCTION: Multiple sclerosis (MS) is the neurological non-traumatic disease that produces permanent incapacity in the young people with the greatest frequency. An almost total consensus exists on the implication of environmental and genetic factors in the pathogenesis of the disease. In a considerable percentage of patients, antecedent relatives of other cases of MS exist, who are separated by other healthy relatives sometimes. AIMS: We try to study the familial antecedents of the MS patients, to locate to the healthy members of the family including in the forced line of the possible genetic transmission of the disease and ruling out subclinical involvement by the use of magnetic resonance imaging (MRI). PATIENTS AND METHODS: We reviewed the familial antecedents of the MS patients followed by the MS Unit of the Service of Neurology of the Hospital Virgen Macarena of Seville. After the accomplishment of their genealogical trees, we identified the cases of familial MS. We locate and practice MRI on the healthy subjects of the family, who are in the genetic line of communication of the disease (obligate carriers). RESULTS AND CONCLUSIONS: We were able to identify 14 obligate carriers of the gene in 12 of the families. In the MRIs that were done, we found MS-compatible lesions in 10 subjects. These findings confirm the existence of silent forms of the disease, that make difficult the knowledge of the genetic implications in the pathogenesis of the disease.
Subject(s)
Brain/pathology , Magnetic Resonance Imaging , Multiple Sclerosis/genetics , Aged , Cohort Studies , Female , Heterozygote , Humans , Male , Middle Aged , Multiple Sclerosis/pathology , Pedigree , Retrospective Studies , Spain/epidemiologyABSTRACT
We have analyzed a CA repeat polymorphism localized 46-kb upstream of the Fas ligand gene in Spanish and American populations that include 139 healthy controls and a cohort of 177 unrelated relapsing and remitting multiple sclerosis (MS) patients. The MS patients consisted of two groups, one with a family history of MS and one without. The frequency of the 13 CA repeats (allele B) was lower (p=0.01) in MS patients than in controls, 0.45 and 0.55 respectively. The odds ratio (BB vs. AB/AA) for MS patients vs. healthy controls was 0.51 (95% CI 0.3-0.9; p=0.01). The odds ratio (BB vs. AB/AA) for MS patients extracted from multiply affected families vs. healthy controls was 0.22 (95% CI 0.07-0.62; p=0.002). The HLA DRB1*1501-DQB1*0602 haplotype is associated with B allele with a relative frequency higher than A allele (0.52 and 0.48 in patients vs. 0.68 and 0.32 in controls). The results suggest that chromosomes with B allele have a genetic background that reduces susceptibility to MS, particularly in the familial forms.
Subject(s)
Membrane Glycoproteins/genetics , Multiple Sclerosis/genetics , Polymorphism, Genetic , Alleles , Apoptosis/immunology , Fas Ligand Protein , Genotype , HLA-DQ Antigens/genetics , HLA-DQ beta-Chains , HLA-DR Antigens/genetics , HLA-DRB1 Chains , Humans , Multiple Sclerosis/immunology , Phenotype , Repetitive Sequences, Nucleic AcidSubject(s)
Brain/pathology , Lateral Medullary Syndrome/diagnosis , Acute Disease , Adult , Humans , Magnetic Resonance Imaging , MaleABSTRACT
No disponible
Subject(s)
Adult , Adolescent , Male , Humans , Gene Expression , Lateral Medullary Syndrome , Point Mutation , Dystonia Musculorum Deformans , Acute Disease , Magnetic Resonance Imaging , TelencephalonABSTRACT
INTRODUCTION: Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system (CNS) with a clear proved genetic susceptibility. The real frequency and clinical features of familial MS is although not well established in Spain. OBJECTIVE: We studied the clinical and CSF features of familial MS (FMS) patients in comparison with the rest of our patients. PATIENTS AND METHODS: We reviewed 308 definite MS patients looking for patients with other familial members with MS. We analyzed clinical characteristics (age, age at onset, sex, evolution time, evolution course, symptoms at onset, disability measured by EDSS scale) and IgG synthesis measured by Tibbling-Link index. RESULTS: We found 23 patients (10 men and 13 women) in 18 independent families with at least other family member diagnosed of definite MS (7.47% of our total MS population). Age and age at onset were no different from non FMS cases. The clinical course was relapsing-remitting in 21 out of 23 FMS cases and secondary progressive in two. No primary progressive cases were found among FMS. At onset the symptom most frequently found in FMS was optic neuritis. Mean EDSS score was lower in FMS cases in comparison with the rest of cases. Link index was increase in 93.7% of patients with FMS. CONCLUSION: In comparison with non familiar forms FMS patients in Spain, present more often remitting courses, are less disabled, optical neuritis is more frequently seen as onset symptom and IgG synthesis is more often increased.