ABSTRACT
To expand current knowledge, we examined the safety and tolerability of subcutaneous interferon ß-1a in patients with pediatric-onset multiple sclerosis. Records from 307 patients who had received at least 1 injection of subcutaneous interferon ß-1a for demyelinating events when aged younger than 18 years were reviewed. Overall, 168 (54.7%) patients had at least 1 prespecified medical event related to or under close monitoring with subcutaneous interferon ß-1a or specific to pediatric patients, 184 (59.9%) had nonserious medical events related to treatment or of unknown causality, and 12 (3.9%) had serious medical events irrespective of causality. The most common laboratory abnormalities were increased alanine (74/195; 37.9%) and aspartate aminotransferase levels (59/194; 30.4%). Annualized relapse rates were 1.79 before treatment and 0.47 during treatment. In conclusion, adult doses of subcutaneous interferon ß-1a (44 and 22 µg, 3 times weekly) were well tolerated in pediatric patients and were associated with reduced relapse rates.
Subject(s)
Adjuvants, Immunologic/administration & dosage , Interferon-beta/administration & dosage , Multiple Sclerosis/drug therapy , Adolescent , Child , Disability Evaluation , Female , Humans , Injections, Subcutaneous , Interferon beta-1a , International Cooperation , Male , Retrospective Studies , Severity of Illness Index , Treatment OutcomeABSTRACT
PURPOSE OF REVIEW: Pediatric-onset multiple sclerosis (MS) is increasingly recognized. Conversely, MS diagnosis in the pediatric population continues to be challenging, particularly in the youngest group of patients. An interesting amount of data has been recently published concerning immunopathogenesis, environmental factors, diagnosis, and treatment of MS in pediatric patients. RECENT FINDINGS: Recent studies have demonstrated that brain MRI criteria may distinguish MS from acute disseminated encephalomyelitis, and from nondemyelinating disorders in children. The presence of native myelin oligodendrocyte glycoprotein antibodies strongly correlates with a particular pediatric MS phenotype. Vitamin D, Epstein-Barr virus infection, and cigarette smoke are risk factors likely to act at specific stages during life. Diffuse tissue damage was confirmed in normal-appearing white matter at early stages of disease in children with MS, pointing to the need for early treatment interventions. The cognitive involvement of MS in children is progressive. SUMMARY: Pediatric-onset MS needs a prompt identification and early treatment. Further multinational research studies are still necessary to advance on genetic, immunologic, and imaging features on the initial and ongoing aspects of this disorder in the pediatric population.
Subject(s)
Multiple Sclerosis , Child , Diagnosis, Differential , Disease Progression , Environment , Humans , Magnetic Resonance Imaging , Multiple Sclerosis/diagnosis , Multiple Sclerosis/drug therapy , Multiple Sclerosis/epidemiology , Multiple Sclerosis/etiologyABSTRACT
BACKGROUND: Paediatric multiple sclerosis accounts for up to 10% of all MS cases. The initial course of the disease is relapsing-remitting in most children, with a relapse rate generally higher than that observed in adult patients. There is published experience on the use of first-line disease modifying therapies in children with MS. However, about 1/3 of paediatric MS cases do not respond to IFN-beta or glatiramer acetate and continue to develop relapses and disease progression. These patients could be proposed to a second-line treatment. METHODS: A comprehensive review of the published literature related to pharmacologic treatment of MS in adults and paediatric patients was performed. The recent literature has been extracted for new evidence from controlled trials in adult patients, and open treatment studies and reported expert opinion in paediatric patients. RESULTS: No disease modifying drug has been approved for the treatment of children and adolescents with MS, although the currently available first-line therapies for adults seem to be safe and well tolerated in this population. Further studies are required to assess the safety and efficacy of second-line treatments in children with MS. CONCLUSION: The present article constitutes an update of the existing publications regarding treatment of acute events of CNS demyelination in children and adolescents as well as considerations for the use of immunomodulatory therapies.
Subject(s)
Multiple Sclerosis/therapy , Adolescent , Adrenal Cortex Hormones/therapeutic use , Child , Clinical Trials as Topic , Glatiramer Acetate , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunomodulation , Immunosuppressive Agents/therapeutic use , Interferon-beta/administration & dosage , Interferon-beta/therapeutic use , Interferons/therapeutic use , Multiple Sclerosis/drug therapy , Peptides/therapeutic use , Plasma ExchangeABSTRACT
The advent of MRI has contributed to increase the interest and awareness in childhood white matter disorders. A major priority is to distinguish transient and self-limited demyelinating syndromes like disseminated encephalomyelitis (DEM), from life-long diseases like multiple sclerosis (MS). However, the term DEM has been inconsistently applied across studies due to the lack of clear clinical and neuroimaging diagnostic criteria. The present review summarizes the available literature on DEM in children, outlines the main clinical and neuroimaging features at presentation, pathogenesis and outcome, and its differentiation from other conditions with acute impact in the CNS. The recently proposed clinical definitions for monophasic disseminated encephalomyelitis and its relapsing variants are discussed, and controversies surrounding the diagnosis of MS in children are addressed.
Subject(s)
Encephalomyelitis, Acute Disseminated/pathology , Autoimmune Diseases/pathology , Child , Diagnosis, Differential , Encephalomyelitis, Acute Disseminated/diagnosis , Encephalomyelitis, Acute Disseminated/epidemiology , Encephalomyelitis, Acute Disseminated/therapy , Humans , Magnetic Resonance Imaging , Multiple Sclerosis/diagnosis , Multiple Sclerosis/pathology , Prognosis , Recurrence , Terminology as TopicABSTRACT
Multiple sclerosis (MS) is usually a disease of young adulthood, its clinical onset occurring between 20 and 40 years of age; however, today there is general consensus that MS can also occur in children, adolescents and even in infants. In order to gain further insight into the T-cell repertoire present in this particular group of patients myelin basic protein (MBP)-, MBP exon-2- and myelin oligodendrocyte glycoprotein (MOG)Igd-specific T-cell lines (TCLs) were isolated from 18 patients whose symptoms had started before the age of 16. Epitope specificity was established by measuring proliferative responses, and interferon-y (IFN-y) secretion by using a panel of overlapping synthetic peptides. For MOGIgd, the T-cell response was focused on three main immunodominant epitopes comprising residues 1-26, 36-60 and 63-87. For MBP the predominant immune responses were directed against peptides 83-102, 139-153 and 146-162. When compared to those observed in adult-onset MS patients, anti-MOGIgd specificity and anti-MBP responses showed similar results. Moreover, the number of MBP exon-2 TCLs isolated, and the magnitude of the specific IFN-gamma secretion induced were similar, both in childhood/juvenile-onset and adult-onset MS patients. Thus, despite differences in the clinical and neuroimaging manifestations of MS, these results would seem to indicate that both the spectrum of MBP found, as well as the MOGIgd epitopes recognized by peripheral blood T cells in MS, appear to be similar for childhood/juvenile-onset and adult-onset patients.
Subject(s)
Multiple Sclerosis, Relapsing-Remitting/immunology , Myelin Basic Protein/immunology , Myelin-Associated Glycoprotein/immunology , T-Lymphocytes/immunology , Adolescent , Age of Onset , Cell Line , Child , Child, Preschool , Cohort Studies , Epitope Mapping , Epitopes, T-Lymphocyte/immunology , Female , Humans , Interferon-gamma/metabolism , Male , Myelin Proteins , Myelin-Oligodendrocyte Glycoprotein , Peptide Fragments/immunology , T-Lymphocytes/cytology , T-Lymphocytes/metabolismABSTRACT
The authors studied the safety and tolerability of subcutaneous interferon beta-1a at different doses in 24 children with clinically definite multiple sclerosis. After a mean treatment period of 44 months, interferon beta-1a was well tolerated in 22 patients, although two experienced possible serious adverse events. Although effectiveness cannot be inferred from this study, the authors did observe a significant reduction in the relapse rate at 22 mug, three times weekly, in the relapsing-remitting subgroup.
Subject(s)
Interferon-beta/therapeutic use , Multiple Sclerosis/drug therapy , Adolescent , Age of Onset , Child , Female , Humans , Immunotherapy , Interferon beta-1a , Interferon-beta/immunology , Male , Multiple Sclerosis/immunology , Prospective Studies , Treatment OutcomeABSTRACT
La encefalomielitis aguda diseminada, la esclerosis múltiple, la neuritis óptica, la mielitis transversa y la neuromielitis óptica son algunos ejemplos de trastornos desmielinizantes, cuyos criterios diagnósticos en adultos son objeto de revisión permanente. Se actualizarán los aspectos importantes de las dos enfermedades desmielinizantes más frecuentes en pediatría. La encefalomielitis aguda diseminada puede ocurrir a cualquier edad, es más frecuente en niños y presenta curso monofásico. Sin embargo, se han descrito algunas formas con recaídas, haciendo difícil su distinción de la esclerosis múltiple. Los pacientes con encefalomielitis aguda diseminada inicial que evolucionan a la esclerosis múltiple varían entre 9.5-27 por ciento. No existe tratamiento estandarizado más allá de las medidas iniciales de sostén. No se ha realizado hasta el momento un ensayo controlado y asignado al azar para su tratamiento en niños o en adultos. El tratamiento con corticoides constituye la terapia más utilizada y mejor tolerada en pacientes pediátricos. El diagnóstico de esclerosis múltiple en pacientes menores de diez años es excepcional. Las características de las neuroimágenes en niños difieren del patrón usual del adulto. La esclerosis múltiple se define como una enfermedad del sistema nervioso central caracterizada por desmielinización, inflamación y daño axonal. La forma evolutiva más frecuente, en niños, es la esclerosis múltiple con recaídas y remisiones (80 por ciento a los diez años), seguida por las formas: secundaria progresiva (26 por ciento) y primaria progresiva (6-14 por ciento). Es necesario reconsiderar el límite inferior de edad para el diagnóstico de esclerosis múltiple, o bien, desarrollar criterios diagnósticos clínicos y radiológicos específicos para pacientes pediátricos. Debe considerarse la particular forma de presentación en los niños menores de diez años y establecer claramente el diagnóstico diferencial con las formas recurrentes y multifásicas ...
Subject(s)
Humans , Encephalomyelitis, Acute Disseminated , Demyelinating Diseases , Multiple SclerosisABSTRACT
La encefalomielitis diseminada aguda (EMDA) es una enfermedad desmielinizante son retrospectivas, con seguimiento a corto plazo. El objetivo de este trabajo es describir una extensa cohorte pediátrica con EMDA, su pronóstico a largo plazo y establecer indicadores clínicos o neuroradiológicos pronósticos. Pacientes y método: estudio prospectivo y longitudinal (1989 2004) en 111 pacientes que cumplieron criterios diagnósticos para EMDA. Resultados: edad de inicio (media) 6 más o menos 3.9 años (rango, 0.4 menos16 años). Antecedente viral o vaccinal en el 79 por ciento. El cuadro de presentación incluyó compromiso de la conciencia (86 por ciento), signos piramidales (82 por ciento), hemi o cuadriparesia aguda (76 por ciento) y ataxia (53 por ciento). Se identificaron cuatro subgrupos por RMN. Los pacientes estudiados no presentaron bandas oligocionales intratecales. El tratamiento con altas dosis de corticoides se asoció con una buena recuperación neurológica y resolución de las lesiones. Seguimiento: media de 8.6 más o menos 3.8 años (rango, 1 a 17 años). El 94 por ciento tuvo una evolución monofásica, y el 6 por ciento restante bifásica. Noventa y ocho niños (88 por ciento) mostraron buena recuperación , con evaluaciones normales o hallazgos semiológicos sin discapacidad actual. No encontramos asociación significativa entre los subgrupos radiológicos y el pronóstico final. La discapacidad residual se asoció con compromiso inicial del nervio óptico. Conclusiones: la EMDA pediátrica puede considerarse una enfermedad de buen pronóstico. Su frecuencia real es mayor que la publicada. Las características de la RMN no tienen valor predictivo pronóstico. Aún en los casos con recaídas, es posible establecer la diferencia entre EMDA y esclorosis múltiple infantil
Subject(s)
Humans , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Encephalomyelitis, Acute Disseminated/diagnosis , Demyelinating Diseases , Magnetic Resonance Spectroscopy , Longitudinal Studies , Prospective Studies , Cohort StudiesABSTRACT
La encefalomielitis diseminada aguda (EMDA) es una enfermedad desmielinizante son retrospectivas, con seguimiento a corto plazo. El objetivo de este trabajo es describir una extensa cohorte pediátrica con EMDA, su pronóstico a largo plazo y establecer indicadores clínicos o neuroradiológicos pronósticos. Pacientes y método: estudio prospectivo y longitudinal (1989 2004) en 111 pacientes que cumplieron criterios diagnósticos para EMDA. Resultados: edad de inicio (media) 6 más o menos 3.9 años (rango, 0.4 menos16 años). Antecedente viral o vaccinal en el 79 por ciento. El cuadro de presentación incluyó compromiso de la conciencia (86 por ciento), signos piramidales (82 por ciento), hemi o cuadriparesia aguda (76 por ciento) y ataxia (53 por ciento). Se identificaron cuatro subgrupos por RMN. Los pacientes estudiados no presentaron bandas oligocionales intratecales. El tratamiento con altas dosis de corticoides se asoció con una buena recuperación neurológica y resolución de las lesiones. Seguimiento: media de 8.6 más o menos 3.8 años (rango, 1 a 17 años). El 94 por ciento tuvo una evolución monofásica, y el 6 por ciento restante bifásica. Noventa y ocho niños (88 por ciento) mostraron buena recuperación , con evaluaciones normales o hallazgos semiológicos sin discapacidad actual. No encontramos asociación significativa entre los subgrupos radiológicos y el pronóstico final. La discapacidad residual se asoció con compromiso inicial del nervio óptico. Conclusiones: la EMDA pediátrica puede considerarse una enfermedad de buen pronóstico. Su frecuencia real es mayor que la publicada. Las características de la RMN no tienen valor predictivo pronóstico. Aún en los casos con recaídas, es posible establecer la diferencia entre EMDA y esclorosis múltiple infantil(AU)