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INTRODUCTION: The primary objective of the core data set is to reduce heterogeneity and promote harmonization among data sources in EM, thereby reducing the time needed to execute real life data collection efforts. Recently, a group led by the Multiple Sclerosis Data Alliance has developed a core data set for collecting real-world data on multiple sclerosis (MS) globally. Our objective was to adapt this global data set to the needs of Latin America, so that it can be implemented by the registries already developed and in the process of development in the region. MATERIAL AND METHODS: A working group was formed regionally, the core data set created globally was adapted (translation process into Spanish, incorporation of regional variables and consensus on variables to be used). Consensus was obtained through the remote Delphi methodology of a round of questionnaires and remote discussion of the core data set variables. RESULTS: A total of 25 professionals from Latin America carried out the adaptation process between November 2022 and July 2023. Agreement was established on a core data set of nine categories and 45 variables, version 2023 to suggest its implementation in developed or developing registries, and MS cohorts in the region. CONCLUSION: The core data set seeks to harmonize the variables collected by registries and cohorts in MS in Latin America in order to facilitate said collection and allow collaboration between sources. Its implementation will facilitate real life data collection and collaboration in the region.
TITLE: Core data set para la generación de datos de la vida real en esclerosis múltiple: adaptación de una iniciativa global para América Latina.Introducción. Los objetivos primarios del core data set son reducir la heterogeneidad y promover la armonización entre las fuentes de datos en la esclerosis múltiple (EM), reduciendo así el tiempo necesario para ejecutar esfuerzos en la recolección de datos de vida real. Recientemente, un grupo liderado por la Multiple Sclerosis Data Alliance ha desarrollado un core data set para la recolección de datos del mundo real en EM a nivel global. Nuestro objetivo ha sido adaptar y consensuar este conjunto de datos globales a las necesidades de América Latina para que pueda ser implementado por los registros ya desarrollados y en proceso de desarrollo en la región. Material y métodos. Se conformó un grupo de trabajo regionalmente y se adaptó el core data set creado globalmente (proceso de traducción al español, incorporación de variables regionales y consenso sobre variables que se iban a utilizar). El consenso se obtuvo a través de la metodología Delphi remoto de ronda de cuestionarios y discusión a distancia de las variables del core data set. Resultados. Veinticinco profesionales de América Latina llevaron adelante el proceso de adaptación entre noviembre de 2022 y julio de 2023. Se estableció un acuerdo sobre un core data set de nueve categorías y 45 variables, versión 2023, con la sugerencia de implementarlo en registros desarrollados o en vías de desarrollo y cohortes de EM en la región. Conclusión. El core data set busca armonizar las variables recolectadas por los registros y las cohortes de EM en América Latina con el fin de facilitar dicha recolección y permitir una colaboración entre fuentes. Su implementación facilitará la recolección de datos de vida real y la colaboración en la región.
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Esclerose Múltipla , Humanos , América Latina/epidemiologia , Esclerose Múltipla/epidemiologia , Comitês Consultivos , Consenso , Sistema de RegistrosRESUMO
Introducción: La encefalitis por anticuerpos contra el receptor N-metil.D.aspartato (NMDA-R) es un trastorno inflamatorio del sistema nervioso central (SNC) en el cual autoanticuerpos dirigidos hacia la subunidad NR1 del receptor N-metil-D aspartato (NMDA) desarrollan un conjunto de síntomas neuropsiquiátricos, convulsiones y movimientos anormales. El tratamiento recomendado incluye metilprednisolona (MP) y gamaglobulina (IVIg), y/o recambio plasmático terapéutico (RPT); y en caso de no respuesta: rituximab (RTX) y/o ciclofosfamida (CFM). Objetivos: Analizar características clínicas, bioquímicas, electroencefalograma (EEG), resonancia magnética (RM) cerebral, tratamientos recibidos y resultados observados en una serie de pacientes con encefalitis autoinmune (EA) probable o confirmada. Materiales y métodos: Analizamos las historias clínicas de pacientes menores a 17 años que cumplían criterios diagnósticos de Graus (2016) para EA probable, con seguimiento mayor a 6 meses, internados en el Hospital Garrahan entre 2008 y 2023. El diagnóstico se definió por la identificación de anticuerpos anti-NMDAR (N-metil D-aspartato) en líquido cefalorraquídeo (LCR) por ensayo basado en células - cell bassed assay (CBA). Resultados: Reunieron criterios de EA probable 94 pacientes con una edad media de 89.5 meses, 51% mujeres. Se dividieron en dos grupos: seropositivos y seronegativos de acuerdo al resultado del biomarcador. Seropositivos 45/94. El síntoma inicial más frecuente fue: convulsiones. El 28% requirió ingreso a Unidad de Cuidados Intensivos (UCI). 4 pacientes seropositivos y 1 seronegativo tuvieron encefalitis por el virus del herpes simple (Om) previamente. En una paciente seronegativa se diagnosticó teratoma ovárico. Hallazgos de estudios complementarios: LCR patológico en el 29%, RM cerebral en el 52%, EEG en el 74%. El tratamiento de primera línea más empleado fue MP + IVIg. El 46% de los pacientes presentó recuperación completa. Entre los pacientes que recibieron RTX, el 65% tuvo una recuperación completa. Ningún paciente que recibió RTX presentó recaída. Conclusión: Ante la sospecha de EA se debe considerar el inicio temprano de inmunoterapia para favorecer la rápida recuperación funcional. Se recomienda el uso temprano de RTX en los casos con presentación grave o respuesta subóptima al tratamiento de primera línea para beneficiar la respuesta clínica y reducir el riesgo de recaída (AU)
Introduction: Encephalitis due to antibodies against the N-methyl-D-aspartate receptor (NMDA-R) is an inflammatory disorder of the central nervous system (CNS) in which autoantibodies directed against the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor develop a set of neuropsychiatric symptoms, seizures, and abnormal movements. The recommended treatment includes methylprednisolone (MP) and intravenous immunoglobulin (IVIg), and/or therapeutic plasma exchange (TPE); and in case of non-response: rituximab (RTX) and/or cyclophosphamide (CFM). Objectives: To analyze clinical, biochemical, electroencephalogram (EEG), magnetic resonance imaging (MRI) of the brain, treatments received, and outcomes observed in a series of patients with probable or confirmed autoimmune encephalitis (AE). Materials and methods: We analyzed the medical records of patients under 17 years of age who met Graus' diagnostic criteria (2016) for probable AE, with follow-up of more than 6 months, hospitalized at Hospital Garrahan between 2008 and 2023. Diagnosis was defined by the identification of anti-NMDAR antibodies (N-methyl D-aspartate) in cerebrospinal fluid (CSF) by cell-based assay (CBA). Results: Ninety-four patients met criteria for probable AE with a mean age of 89.5 months, 51% female. They were divided into two groups: seropositive and seronegative according to the biomarker result. Seropositive 45/94. The most frequent initial symptom was seizures. Twenty-eight percent required admission to the Intensive Care Unit (ICU). Four seropositive patients and one seronegative patient had previously had herpes simplex encephalitis (Om). Ovarian teratoma was diagnosed in one seronegative patient. Findings of complementary studies: Pathological CSF in 29%, brain MRI in 52%, EEG in 74%. The most commonly used first-line treatment was MP + IVIg. Forty-six percent of patients experienced complete recovery. Among patients who received RTX, 65% had complete recovery. No patient who received RTX experienced relapse. Conclusion: In the suspicion of AE, early initiation of immunotherapy should be considered to promote rapid functional recovery. Early use of RTX is recommended in cases with severe presentation or suboptimal response to first-line treatment to benefit clinical response and reduce the risk of relapse (AU)
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Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Autoanticorpos , Encefalite , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/tratamento farmacológico , Imunoterapia , Convulsões , Espectroscopia de Ressonância Magnética , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Case introduction: In this work we present a female infant patient with epilepsy of infancy with migrating focal seizures (EIMFS). Although many pharmacological schemes were attempted, she developed an encephalopathy with poor response to antiepileptic drugs and progressive cerebral dysfunction. Aim: To present the pharmacological response and therapeutic drug monitoring of a paediatric patient with a severe encephalopathy carrying a genetic variant in KCNT1 gene, whose identification led to include quinidine (QND) in the treatment regimen as an antiepileptic drug. Case report: Patient showed slow rhythmic activity (theta range) over left occipital areas with temporal propagation and oculo-clonic focal seizures and without tonic spasms three months after birth. At the age of 18 months showed severe impairments of motor and intellectual function with poor eye contact. When the patient was 4 years old, a genetic variant in the exon 24 of the KCNT1 gene was found. This led to the diagnosis of EIMFS. Due to antiepileptic treatment failed to control seizures, QND a KCNT1 blocker, was introduced as a therapeutic alternative besides topiramate (200 mg/day) and nitrazepam (2 mg/day). Therapeutic drug monitoring (TDM) of QND plasma levels needed to be implemented to establish individual therapeutic range and avoid toxicity. TDM for dose adjustment was performed to establish the individual therapeutic range of the patient. Seizures were under control with QND levels above 1.5 mcg/ml (65-70 mg/kg q. i.d). In addition, QND levels higher than 4.0 mcg/ml, were related to higher risk of suffering arrhythmia due to prolongation of QT segment. Despite initial intention to withdrawal topiramate completely, QND was no longer effective by itself and failed to maintain seizures control. Due to this necessary interaction between quinidine and topiramate, topiramate was stablished in a maintenance dose of 40 mg/day. Conclusion: The implementation of Precision Medicine by using tools such as Next Generation Sequencing and TDM led to diagnose and select a targeted therapy for the treatment of a KCNT1-related epilepsy in a patient presented with EIMFS in early infancy and poor response to antiepileptic drugs. QND an old antiarrhythmic drug, due to its activity as KCNT1 channel blocker, associated to topiramate resulted in seizures control. Due to high variability observed in QND levels, TDM and pharmacokinetic characterization allowed to optimize drug regimen to maintain QND concentration between the individual therapeutic range and diminish toxicity.
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INTRODUCTION: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed. OBJECTIVE: To survey the current global clinical practice of clinicians treating MOGAD. METHOD: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019). RESULTS: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT. CONCLUSION: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.
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Autoanticorpos , Imunoglobulinas Intravenosas , Adulto , Criança , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Glicoproteína Mielina-Oligodendrócito , Plasmaferese , Inquéritos e QuestionáriosRESUMO
Neuromyelitis optica (NMO) is an inflammatory autoimmune disease of the central nervous system that preferentially targets the optic nerves and spinal cord. The clinical presentation may suggest multiple sclerosis (MS), but a highly specific serum autoantibody against the astrocytic water channel aquaporin-4 present in up to 80% of NMO patients enables distinction from MS. Optic neuritis may occur in either condition resulting in neuro-anatomical retinal changes. Optical coherence tomography (OCT) has become a useful tool for analyzing retinal damage both in MS and NMO. Numerous studies showed that optic neuritis in NMO typically results in more severe retinal nerve fiber layer (RNFL) and ganglion cell layer thinning and more frequent development of microcystic macular edema than in MS. Furthermore, while patients' RNFL thinning also occurs in the absence of optic neuritis in MS, subclinical damage seems to be rare in NMO. Thus, OCT might be useful in differentiating NMO from MS and serve as an outcome parameter in clinical studies.
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Esclerose Múltipla/diagnóstico , Neuromielite Óptica/diagnóstico , Neurite Óptica/diagnóstico , Neurônios Retinianos/ultraestrutura , Tomografia de Coerência Óptica/métodos , HumanosRESUMO
INTRODUCTION. Multiple sclerosis (MS) it is not considered any more a rare disease in Latin America. Most of the Latin American countries have reported moderate or lower prevalence data. However only very few countries have developed therapeutic guidelines. LACTRIMS prepared this consensus document with specific recommendations for the treatment of the disease. DEVELOPMENT. Experts on treatment and clinical research on MS were invited by LACTRIMS in order to generate a initial document to be discussed in Quito, Ecuador. Several groups were organized in relation of the different clinical variants. These groups were coordinated by experts leaders and prepared a preliminary document that was discussed in Quito during July 8th and 9th, 2011. Finally the final version was submitted to the members and delegates of LACTRIMS in most of the Latin American countries who were able to make modifications and suggest changes to the final manuscript. CONCLUSIONS. Based on the different evidence levels and the AGREE criteria, the clinical variants were reviewed and recommendations were made for the use of drugs and different modifying disease therapeutic agents.
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Esclerose Múltipla/tratamento farmacológico , Humanos , Esclerose Múltipla/complicaçõesRESUMO
New therapies are being evaluated by clinical trials and, if efficacious, introduced for the treatment of adult MS. The role of these new and existing agents in the management of pediatric MS has yet to be defined. Pediatric investigation plans are now required by the Food and Drug Administration and European Medicines Agency for approval of new biological agents, providing an important opportunity to gather much-needed data for clinicians caring for children and adolescents with MS. However, challenges include the small number of patients, and the need for efficient yet comprehensive study designs incorporating factors necessary to inform the clinical care of children with MS. The elected Steering committee of the International Pediatric MS Study Group (IPMSSG) conducted a structured review of existing data on the disease-modifying therapies in pediatric MS and developed a consensus statement, which was further modified by the IPMSSG general membership, using an online survey tool. Fifty-one IPMSSG members from 21 countries responded to the survey, and 50 approved the final statement. Consensus recommendations regarding use of existing first- and second-line therapies, as well as a proposed definition for inadequate treatment response, are presented. Recommendations for the use and evaluation of emerging therapies (currently in phase III clinical trials or recently approved for adult MS) are discussed. The IPMSSG endorses the inclusion of pediatric MS patients in trials evaluating appropriate new and emerging therapies. Mechanisms for conducting high-impact, multicenter studies, including long-term follow-up in pediatric MS, are required to ensure that all MS patients, irrespective of age, benefit from advances in MS therapeutics.
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Fatores Imunológicos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adolescente , Criança , HumanosRESUMO
Anti-myelin basic protein (MBP) antibodies in pediatric-onset MS and controls were characterized. Serum samples were obtained from 94 children with MS and 106 controls. Paired CSF and serum were obtained from 25 children with MS at time of their initial episode of acute demyelinating syndrome (ADS). Complementary assays were applied across samples to evaluate the presence, and the physical binding properties, of anti-MBP antibodies. While the prevalence and titers of serum anti-MBP antibodies against both immature and mature forms of MBP were similar in children with MS and in controls, binding characteristics and formal Surface Plasmon Resonance (SPR) studies indicated surprisingly high binding affinities of all pediatric anti-MBP antibodies. Serum levels of anti-MBP antibodies correlated significantly with their CSF levels, and their presence in children with MS was associated with significantly increased risk of an acute disseminated encephalomyelitis-like initial clinical presentation. While antibodies to both immature and mature forms of MBP can be present as part of the normal pediatric humoral repertoire, these anti-myelin antibodies are of surprisingly high affinity, can access the CNS during inflammation, and have the capacity to modulate disease expression. Our findings identify an immune mechanism that could contribute to the observed heterogeneity in spectrum of clinical presentations in early-onset MS.
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Autoanticorpos/fisiologia , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/imunologia , Bainha de Mielina/imunologia , Proteínas do Tecido Nervoso/imunologia , Fatores de Transcrição/imunologia , Doença Aguda , Adolescente , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Esclerose Múltipla/sangue , Esclerose Múltipla/líquido cefalorraquidiano , Proteína Básica da Mielina , Proteínas do Tecido Nervoso/sangue , Proteínas do Tecido Nervoso/líquido cefalorraquidiano , Fatores de Risco , Síndrome , Fatores de Transcrição/sangue , Fatores de Transcrição/líquido cefalorraquidiano , Adulto JovemRESUMO
OBJECTIVE: To determine seroprevalence of neuromyelitis optica (NMO)-IgG in childhood CNS inflammatory demyelinating disorders. METHODS: We analyzed demographic, clinical, and radiologic data in a blinded fashion and assessed serum NMO-IgG status for 87 children: 41 with relapsing-remitting multiple sclerosis (RRMS), 17 with NMO, 13 with monophasic/recurrent optic neuritis (ON), 13 with transverse myelitis, of whom 10 were longitudinally extensive on MRI spine (LETM), and another 3 with LETM in the context of acute disseminated encephalomyelitis (ADEM). RESULTS: Ten of the 87 children (11%) were seropositive. Eight of 17 with NMO (47%) were seropositive (7 of 9 with relapsing NMO [78%], 1 of 8 with monophasic NMO [12.5%]). Two other children were seropositive: 1 of 5 with recurrent ON and one child with recurrent LETM. No seropositive case was identified among 41 with RRMS (14% of whom had LETM at some point in their clinical course), 8 with monophasic ON, 9 with monophasic LETM, or 3 with LETM in the context of ADEM. CONCLUSIONS: The similar frequency of neuromyelitis optica (NMO)-IgG in both childhood and adult cases of NMO, and its rarity in relapsing-remitting multiple sclerosis, supports the concept that these diseases have a similar pathogenesis in childhood and adulthood. It is noteworthy that none of nine children with monophasic longitudinally extensive transverse myelitis (LETM) was NMO-IgG-seropositive. Furthermore, LETM does not appear to be as predictive of an NMO spectrum disorder in children as it is in adults. Longitudinal studies of larger pediatric LETM cohorts are required to ascertain whether the absence of NMO-IgG is a negative predictor for relapse in this childhood entity.
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Autoanticorpos/sangue , Encefalomielite/sangue , Imunoglobulina G/sangue , Esclerose Múltipla Recidivante-Remitente/sangue , Mielite Transversa/sangue , Neuromielite Óptica/sangue , Doença Aguda , Adolescente , Autoanticorpos/imunologia , Criança , Pré-Escolar , Encefalomielite/diagnóstico , Encefalomielite/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia , Lactente , Masculino , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Esclerose Múltipla Recidivante-Remitente/imunologia , Mielite Transversa/diagnóstico , Mielite Transversa/imunologia , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/imunologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estudos Soroepidemiológicos , Medula Espinal/patologiaRESUMO
Studies in adult patients with multiple sclerosis (MS) suggest significant benefit of early treatment initiation. However, there are no approved therapies for children and adolescents with MS. For adult MS, tolerability and efficacy of several immunomodulatory and immunosuppressive drugs have been demonstrated. Guidelines for the use of these MS therapies in children do not exist. Several small cohort studies of the safety and tolerability of disease-modifying therapies (DMT) in children and adolescents with MS have been recently reported. The side effects of interferon beta (IFNB) and glatiramer acetate (GA) appear to be similar to those reported by adults. The long-term tolerability and safety have yet to be established and efficacy data have yet to be studied. In view of the potential for significant long-term physical and cognitive disability in children with MS, and recent evidence that initiation of immunomodulatory therapy early in the course of MS improves long-term prognosis, an increasing number of children and adolescents with MS are being offered the DMT approved for adults. This review summarizes current knowledge of DMT in pediatric MS and experience in several centers treating pediatric MS and MS variants such as neuromyelitis optica or Devic disease, Balo concentric sclerosis, Marburg acute MS, and Schilder disease (myelinoclastic diffuse sclerosis). Finally, an overview of symptomatic MS therapies and experiences with these treatments in pediatric patients is provided.
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Esclerose Múltipla/terapia , Adolescente , Adulto , Criança , Progressão da Doença , Humanos , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/fisiopatologia , Pediatria , Prognóstico , Recidiva , Resultado do TratamentoRESUMO
INTRODUCTION: Considerable progress has been made in the treatment of patients with relapsing-remitting multiple sclerosis (MS) over the last decade. Exactly how these changes are reflected in daily practice, however, is still not very well known. AIM: To hold interactive workshops so as to be able to evaluate the opinions of Latin-American neurologists about the therapeutic decisions taken with regard to MS. MATERIALS AND METHODS: By means of an interactive voting system, professionals attending each workshop replied to ten pre-established questions about when to start treatment, the use of magnetic resonance imaging (MRI) to supervise treatment, the definition of therapeutic failure and the role of treatment using immunosuppressants. The results were compared with those obtained in similar workshops attended by European and North American neurologists held six months earlier. RESULTS: The use of immunomodulators was considered to be useful in isolated demyelinating syndromes, as 40-50% endorsed their use in clinically stable patients. MRI was seen to be the most sensitive method of monitoring the effectiveness of the therapy -70.6% of them proposed the application of annual scans, which suggests a more frequent use in Latin America than in Europe or the USA. On defining therapeutic failure, the clinical criteria were more important than the MRI scan, and a switch from beta interferons to glatiramer acetate or vice versa was recommended. Treatment with immunosuppressants was considered to be useful in reducing the accumulated disability, but there was no agreement on how to use them. In Latin America, decisions about when to begin treatment seem to lie somewhere between the more favourable posture adopted in USA and the more conservative stance in Europe. CONCLUSIONS: This survey reflects the controversies that affect the therapeutic decisions concerning MS in Latin America and highlights the areas in which more data are needed to optimise the standards of treatment.
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Tomada de Decisões , Esclerose Múltipla Recidivante-Remitente/terapia , Padrões de Prática Médica/normas , Conferências de Consenso como Assunto , Humanos , Imunossupressores/uso terapêutico , América Latina , Imageamento por Ressonância Magnética , Esclerose Múltipla Recidivante-Remitente/patologia , Neurologia , Inquéritos e Questionários , Falha de Tratamento , Recursos HumanosRESUMO
BACKGROUND: Immunomodulatory therapies are widely used in adults with multiple sclerosis (MS) and safety and tolerability is well-established. Although at least 5% of all patients with MS experience the clinical onset of their disease prior to age 18 years, the available literature on safety and tolerability of immunomodulatory therapies for pediatric-onset MS is limited. METHODS: The authors retrospectively reviewed safety and tolerability of interferon beta-1b (IFNbeta-1b) in a cohort of 43 children and adolescents treated for a mean of 29.2 months (SD 22.3 months). RESULTS: Mean age at start of IFNbeta-1b treatment was 13 years. Eight children were < or =10 years. Most common adverse events included flu-like syndrome (35%), abnormal liver function test (26%), and injection site reaction (21%). No serious or unexpected adverse events were reported. CONCLUSIONS: Although data on long-term effects on the maturing organ systems are lacking, the safety profile supports the safety and tolerability of interferon beta-1b (IFNbeta-1b) in children with multiple sclerosis and related diseases. All patients treated with IFNbeta-1b should undergo regular monitoring of liver function.
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Adjuvantes Imunológicos/uso terapêutico , Interferon beta/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Adolescente , Criança , Humanos , Interferon beta-1b , Interferon beta/efeitos adversos , Testes de Função Hepática , Monitorização Fisiológica , Estudos Retrospectivos , SegurançaRESUMO
Objetivos: conocer el nivel cognitivo global y el impacto familiar en un grupo de niños con epilepsias de dificil control, posibles candidatos a tratamiento quirúrgico. Material y método: la muestra estuvo constituida por 100 niños (edad media 11.2 años). El nivel cognitivo global se evaluó con un test de inteligencia general (Stanford-Binet, Wechsler). El impacto sobre la familia se estimó a través de una encuesta donde se consideró la percepción subjetiva de los padres acerca del nivel de calidad de vida de sus hijos. Resultados. Nivel cognitivo: el 58 por ciento registra retraso mental de grado leve a grave (Organización Mundial de la Salud OMS) el 11 por ciento tiene un cociente intelectual promedio y el 31 por ciento restante se sitúa en la franja de normal bajo y limítrofe. Percepción subjetiva de calidad de vida: 12 por ciento mala o muy mala, 40 por ciento regular, 37 por ciento buena, y 11 por ciento muy buena. Conclusiones. coincidente con otras investigaciones los niños con epilepsias refractantes registran un nivel intelectual inferior al término medio, lo cual refleja un grado variable pero claramente significativo de afectación cognitiva. De acuerdo a la percepción de sus padres, la calidad de vida es mala o regular en el 52 por ciento de los casos. Estos datos confirman la importancia de buscar medidas terapéuticas más efectivas, incluyendo un eventual tratamiento quirúrgico con el objeto de evitar o detener el deterioro cognitivo y mejorar la calidad de vida (presente y futura)de estos niños
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Humanos , Pré-Escolar , Criança , Adolescente , Qualidade de Vida , Cognição , Epilepsia , Processos Mentais , Relações Familiares , Deficiência IntelectualRESUMO
BACKGROUND AND PURPOSE: Moyamoya syndrome is an uncommon chronic occlusive cerebrovascular disease in children. The origin of moyamoya syndrome remains undetermined. The role of the prothrombotic disorders contributing to its pathogenesis has not been completely elucidated. The purpose of this study was to determine the frequency of prothrombotic disorders in a pediatric population with moyamoya syndrome. METHODS: From May 1992 to April 2000, a prospective study of 10 consecutive children with moyamoya syndrome was carried out at a single center. Evaluation included the following assays: protein C, protein S, antithrombin, plasminogen, activated protein C resistance, factor V Leiden, and prothrombin gene mutations. Lupus anticoagulant, anticardiolipin antibodies, and anti-beta(2)-glycoprotein I antibodies assays were also performed. The clinical characteristics, underlying diseases, family history of thrombosis, radiological findings, treatment, and outcome were also recorded. RESULTS: In our series, prothrombotic disorders were detected in 4 patients (40%). Inherited protein S deficiency was found in 1 patient; lupus anticoagulant and anticardiolipin antibodies were detected in the remaining 3 patients. One presented persistent lupus anticoagulant for 2.7 years until his death. In the case of the other 2 patients, 1 has maintained lupus anticoagulant for 9 months, whereas the other has kept anticardiolipin/anti-beta(2)-glycoprotein I antibodies for 10 months. CONCLUSIONS: We report the hemostatic data of the largest prospective pediatric study carried out at a single center in the western hemisphere. In 4 patients (40%), a prothrombotic disorder was detected. It is tempting to speculate that these hemostatic abnormalities may contribute to the pathogenesis of moyamoya syndrome in some of our patients.
Assuntos
Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/diagnóstico , Doença de Moyamoya/complicações , Adolescente , Adulto , Anticorpos Anticardiolipina/sangue , Anticorpos Antifosfolipídeos/sangue , Aspirina/uso terapêutico , Transtornos da Coagulação Sanguínea/terapia , Testes de Coagulação Sanguínea , Revascularização Cerebral/efeitos adversos , Criança , Pré-Escolar , Feminino , Fibrinolíticos/uso terapêutico , Glicoproteínas/imunologia , Humanos , Lactente , Inibidor de Coagulação do Lúpus/sangue , Masculino , Pessoa de Meia-Idade , Doença de Moyamoya/imunologia , Doença de Moyamoya/terapia , Estudos Prospectivos , Deficiência de Proteína S/complicações , Deficiência de Proteína S/diagnóstico , Deficiência de Proteína S/terapia , Fatores de Risco , Taxa de Sobrevida , Falha de Tratamento , Resultado do Tratamento , beta 2-Glicoproteína IRESUMO
OBJECTIVES: To stress that different atypical evolutions occur in the course of disease in some patients with the so called benign partial epilepsies of childhood (BPEC). To promote interest in finding clinical and/or electroencephalographic clues to recognize which patients might be prone to present these risks. METHODS: Follow up of 26 pediatric patients who started with typical clinical and EEG features of benign childhood epilepsy with centro-temporal spikes (BCECTS) but presented reversible or persistent serious epileptic events including status epilepticus and language, cognitive or behavioral impairments. Repeated neurological examinations, EEG records and neuropsychological evaluations were done in the course of up to 14 years. Brain imaging studies (CAT and/or MRI) were obtained in all patients. RESULTS: Four groups of patients were recognized: 11 children with atypical benign partial epilepsy of childhood (ABPEC) followed during 4 to 13 years. All have finally recovered and attend normal schools, although five have learning difficulties. Three patients met diagnostic criteria for Landau-Kleffner syndrome (LKS). Two of them recovered from aphasia and in one, some language difficulties persist. Seven children showed status epilepticus of BCECTS but all of them are now normal after 3 to 14 years of follow-up. Five children showed mixed features of the three groups mentioned above and three of them fulfilled the criteria for diagnosis of the syndrome of continuous spike-wave during slow sleep (CSWS). CONCLUSIONS: A small proportion of cases starting with BCECTS evolve into either ABPEC, LKS, status of BCECTS or the syndrome of CSWS. Then, BCECTS is not always benign. Clinical and EEG markers should be sought to predict these atypical evolutions.
Assuntos
Encéfalo/fisiopatologia , Epilepsia Rolândica/fisiopatologia , Anticonvulsivantes/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Criança , Pré-Escolar , Eletroencefalografia , Epilepsia Rolândica/diagnóstico , Epilepsia Rolândica/tratamento farmacológico , Potenciais Somatossensoriais Evocados/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Sono/fisiologia , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: To emphasize that, in some patients, different atypical evolutions occur in the course of so-called benign focal epilepsies of childhood (BFEC) and to promote interest in finding clinical and/or electroencephalographic (EEG) clues to which patients might be prone to these risky evolutions. METHODS: Twenty-six patients who started with the typical clinical and EEG features of benign childhood epilepsy with centrotemporal spikes (BCECTS) but who had reversible or persistent, serious epileptic events including status epilepticus and language, cognitive, or behavioral impairments were followed for =14 years. Repeated neurologic examinations, EEG records, and neuropsychological evaluations were done, and brain-imaging studies [computerized axial tomography (CAT) or magnetic resonance imaging (MRI)] were obtained in all patients. RESULTS: The 26 patients were in four separate groups according to the nature of their atypical evolution. Eleven children had atypical benign focal epilepsy of childhood (ABFEC), three with Landau-Kleffner syndrome (LKS), seven with status epilepticus of BCECTS, and five with mixed features of the other three groups. All the children whose BCECTS evolved into ABFEC have finally recovered and are attending normal schools, although five have learning difficulties. Two of the three patients diagnosed with LKS recovered from aphasia, although some language difficulties persist in one. The seven who showed status epilepticus of BCECTS are now normal after 3-14 years of follow-up, and three of the five children showing mixed features fulfilled the criteria for a diagnosis of epilepsy with continuous spikes and waves during slow sleep (CSWS). CONCLUSIONS: A small proportion of cases starting with BCECTS evolve into ABFEC, LKS, status of BCECTS, or epilepsy with CSWS. In such cases, BCECTS is not always benign. Clinical and EEG markers should be sought to predict these atypical evolutions.
Assuntos
Epilepsia Rolândica/diagnóstico , Adolescente , Fatores Etários , Idade de Início , Encéfalo/anatomia & histologia , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Comorbidade , Eletroencefalografia/estatística & dados numéricos , Epilepsia Rolândica/epidemiologia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos/estatística & dados numéricos , Prognóstico , Estudos Prospectivos , Sono/fisiologia , Estado Epiléptico/diagnóstico , Estado Epiléptico/epidemiologia , Tomografia Computadorizada por Raios XRESUMO
From June 1988 to June 1998, 60 children with extratemporal epilepsies (EE), most of whom were symptomatic, underwent surgery. All patients were studied by means of CT scanning, MRI and scalp EEG. Video-telemetry was used in 40 cases. Intracranial electrodes were placed in 10. Intraoperative ECoG was used in the 35 children who underwent resective procedures and in the 25 in whom disconnection was performed. Surgical procedures were as follows: 24 lesionectomies, 25 disconnecting procedures, 7 polectomies and/or lobectomies, 3 corticectomies and 1 anatomical hemispherectomy. After at least 1 year's follow-up in 48 children, to date 38 are in Engel class I, 7 in class II, 1 in class III and 2 in class IV. That is to say, in 46 of the 48, surgical outcomes ranges from very good to at least worthwhile, as reflected in their classification in Engel class III.
Assuntos
Epilepsia/cirurgia , Procedimentos Neurocirúrgicos , Seleção de Pessoal , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Epilepsia/diagnóstico , Epilepsia/diagnóstico por imagem , Epilepsia/fisiopatologia , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Monitorização Intraoperatória , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: Rasmussen's encephalitis is a neurological disorder probably of immunological origin, characterized by intractable epilepsy, neurological deterioration and the presence of antibodies against R3 glutamate receptors. OBJECTIVE: To present the experience of an Argentinian Paediatric Neurology Service during the past 7 years. MATERIAL AND METHODS: We analyzed the clinical histories of 12 patients with RS as defined by the diagnostic criteria proposed by Hart et al. We evaluated the following parameters: neurological examination, neuropsychological assessment, types of crises, age of onset, frequency, distribution, electroencephalogram, video EEG, evoked potentials, neuro-radiological studies; CT and cerebral MR using gadolinium, SPECT, lumbar puncture and cerebral biopsy. RESULTS: The crises were of simple partial motor type in 12 cases, secondarily generalized partial crises in 7 cases, complex partial crises in 4 cases and partial and generalized motor states in 8 cases. RESULTS. The ictal EEGs during the continuous partial crises showed contralateral focal slow activity of the affected side of the body in 30% of cases. The neuro-radiological studies (CT and MR) showed signs of cerebral hemiatrophy in all 12 cases, hyper-intense images in the T2 sequences of the fronto-temporo-parietal regions in 5 cases, an asymmetric megacisterna magna in 1 case and hypoplasia of the cerebellar vermis in another case. CONCLUSIONS: The continuous partial crises showed little correlation with the electro-encephalography. Following administration of i.v. gammaglobulin there was a transient halt in progression of the neurological deterioration and control of the crises in 55% of the cases. Surgery continued to be the treatment recommended for control of the epileptic crises.
Assuntos
Doenças Autoimunes/epidemiologia , Encefalite/epidemiologia , Epilepsias Parciais/epidemiologia , Hemiplegia/epidemiologia , Adolescente , Adulto , Idade de Início , Atrofia , Autoanticorpos/imunologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Encéfalo/patologia , Criança , Diagnóstico por Imagem , Eletroencefalografia , Encefalite/diagnóstico , Encefalite/imunologia , Encefalite/terapia , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/imunologia , Epilepsias Parciais/terapia , Potenciais Evocados , Feminino , Hemiplegia/diagnóstico , Hemiplegia/imunologia , Hemiplegia/terapia , Humanos , Masculino , Testes Neuropsicológicos , Receptores de Glutamato/imunologia , SíndromeRESUMO
INTRODUCTION: Prospective study to evaluate efficacy of ketogenic diet (KD) in the treatment of children with intractable epilepsies (IE). Tolerability of the KD was also considered. MATERIAL AND METHODS: Criteria for inclusion were: 1. Epilepsy refractary to treatments with antiepileptic drugs (AED) in monotherapy and combining two or three AED. 2. Acknowledgment of blood levels of these drugs in therapeutic range. 3. Absence of liver or kidney disease, metabolic abnormalities, inborn errors of metabolism or other progressive encephalopathies. 4. Family supposedly in economic and psychologic conditions to accept the difficulties of strictly maintaining KD. We used a classic KD following the criteria suggested by the John Hopkins Pediatrics Epilepsy Center. Baseline neurological and physical examination, EEG, blood chemistry including lipid profile were obtained prior to initiative and during the KD. KD efficacy was measured as percent reduction of baseline seizures frequency, considering positive results as reductions of 50% or over. Acceptance of the diet and quality of life were specially considered. Eighteen patients with ages from 2 to 11 years were admitted. Ten of them were males. Diagnosis followed the last Classification of Epileptic Syndromes of the ILAE, and distribution was: Symptomatic partial epilepsies, 8 cases (one had West syndrome at age 5 months); cryptogenic partial epilepsies, 1 case; Lennox-Gastaut syndrome, 2 cases; severe myoclonic epilepsy of infancy, 6 cases and epilepsy with myoclonic astatic seizures 1 case. RESULTS: Four patients were not able to achieve persistent ketosis either due to patient's rejection of KD or to parents non compliance. KD was kept for at least two months before considering failures. Five patients did not show significant improvement and KD was stopped. At present nine patients have been on KD from 6 to 24 months (average 16 months). Four of them showed a 75-100% reduction in seizures frequency and in three the reduction was of 50-75%. CONCLUSIONS: KD was fairly well tolerated by 14 of 18 children and their families. Fifty percent of the 14 patients complying KD showed significant improvement in seizure frequency and in quality of life. Due to the small number of patients and short follow-up, we can not speculate about results in relation to each epileptic syndrome, neither the risk of late complications.