RESUMO
El desarrollo de nuevos abordajes terapéuticos ha generado un aumento en la esperanza de vida de los pacientes con enfermedades neuromusculares (ENM). Se trata de un grupo de enfermedades heterogéneas desde la clínica y los posibles tratamientos. La transición en los pacientes con ENM, implica un gran desafío por presentar niveles intelectuales dentro de rangos promedio, compromisos motor, respiratorio y cardiológico progresivos que resulta en aumento de la dependencia física conforme aumenta la necesidad de autonomía emocional del adolescente. La descripción de transiciones exitosas en ENM incluye intervenciones psicosociales individuales o grupales con un enfoque multidimensional e interdisciplinario, que contemple la participación de la familia para reducir la ansiedad y la preocupación sobre sus hijos. En el Hospital Garrahan los pacientes con ENM son atendidos dentro del Programa de Atención, Docencia e Investigación de Pacientes con Enfermedad Neuromuscular desde 2008. En este trabajo nos proponemos describir la experiencia en transición pre y post pandemia, de los adolescentes con ENM en seguimiento en el Hospital de Pediatría Garrahan (AU)
The development of new care and therapeutic approaches has generated an increase in the life expectancy of patients with neuromuscular diseases (NMD), a group of heterogeneous diseases from a clinical point of view. The transition in patients with MND involves a great challenge due to progressive motor, respiratory and cardiological compromises that result in an increase in physical dependence as the adolescent needs emotional autonomy. The description of successful transitions in patients with MND includes individual and psychosocial interventions with a multidimensional and interdisciplinary approach with family participation. Since 2008, we developed a Care, Teaching and Research Program for Patients with NMD Disease at the Garrahan Hospital. The objective of this work is to describe the pre- and post-pandemic transition experience of adolescents with NMD follow-up in our hospital (AU)
Assuntos
Humanos , Adolescente , Planejamento de Assistência ao Paciente , Transição para Assistência do Adulto/organização & administração , Doenças Neuromusculares/terapia , Equipe de Assistência ao Paciente , Família , Doença Crônica , Hospitais PediátricosRESUMO
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)
Assuntos
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
Introducción: El desarrollo de la tolerancia inmunológica frente a los autoantígenos se denomina autotolerancia. La Diabetes Mellitus tipo 1A (1ADM) es un trastorno metabólico secundario a la destrucción autoinmune de las células beta pancreáticas e insulitis. La miastenia grave (MG) es una enfermedad autoinmune causada por el bloqueo postsináptico de la placa mioneural por AAcs contra los receptores de acetilcolina (ACRA) o contra moléculas de la membrana postsináptica. La asociación entre DM1A y MG se puede observar en el síndrome poliglandular tipo III, caracterizado por enfermedad autoinmune de la glándula tiroides asociada con otras entidades autoinmunes. Método: Reporte de Casos, cuatro pacientes entre 7-19 años, con asociación de MG y DM1A atendidos en el Hospital Garrahan. Conclusión: La Tiroiditis de Hashimoto y la Enfermedad Celíaca son las enfermedades autoinmunes relacionadas más frecuentemente con DM1A en nuestra población. La bibliografía describe la asociación de MG y Tiroiditis de Hashimoto y su coexistencia con DM1A se describe en el Síndrome Poliglandular III. En este trabajo presentamos 4 casos de DM1A asociado con MG fuera de dicho síndrome (AU)
Introduction: The development of immune tolerance to autoantibodies (AAbs) is referred to as self-tolerance. Type 1A Diabetes Mellitus (1ADM) is a metabolic disorder secondary to autoimmune destruction of pancreatic beta cells and insulitis. Myasthenia gravis (MG) is an autoimmune disease caused by postsynaptic blockade of the myoneural plate by AAbs against acetylcholine receptors (Acra) or against postsynaptic membrane molecules. The association between 1ADM and MG may be observed in polyglandular syndrome type III, characterized by autoimmune disease of the thyroid associated with other autoimmune conditions. Methods: Case report; four patients between 7-19 years old, with an association of MG and 1ADM seen at the Garrahan Hospital. Conclusion: Hashimoto's thyroiditis and celiac disease are autoimmune diseases most frequently related to 1ADM in our population. In the literature, the association of MG and Hashimoto's thyroiditis has been described and its coexistence with 1ADM is reported in polyglandular syndrome III. In this study we present 4 cases of 1ADM associated with MG unrelated to this syndrome. (AU)
Assuntos
Humanos , Criança , Adolescente , Doenças Autoimunes , Poliendocrinopatias Autoimunes/diagnóstico , Diabetes Mellitus Tipo 1/complicações , Miastenia Gravis/complicações , Doença Crônica , Estudos TransversaisRESUMO
BACKGROUND: SMA1 natural history is characterized by early development of chronic respiratory failure. Respiratory interventions in type 1 SMA infants are subject to great practice variability. Nusinersen, has been recently approved in Argentina. The advent of novel treatments has highlighted the need for natural history studies reporting disease progression in type 1 SMA. OBJECTIVE: To analyze the progression, respiratory interventions and survival based on the type of respiratory support in type 1SMA patients, in a third level pediatric hospital in Argentina. METHODS: Cohort of SMA1 patients followed at the Interdisciplinary Program for the Study and Care of Neuromuscular Patients (IPNM). Patient survival was analyzed by using the Kaplan-Meier method. Log-rank test was performed to compare the survival curve for three respiratory intervention groups. RESULTS: 59 patients. Mean age of symptom onset was 2.19 (±1.4) months, age at diagnosis was 3.9 (±2.1) months. Patients developed respiratory failure at 5.82 months (±2.32) and 13.8 months (±5.6) in Type 1B and Type 1C, respectively (pâ<â0.001) 53 p were SMA1B. Three copies were found in 1/6 SMA1C. Respiratory interventions: SRC 23 p (56.1%); SRCâ+âNIV 8 p (19.5%); SRCâ+âIV 10 p (24.4%). 8 patients were already on invasive ventilation when included in the IPNM. Patients with invasive ventilation showed longer survival. CONCLUSIONS: This series provides valuable information on respiratory intervention requirements and life expectancy in children with SMA1 before the implementation of novel treatments that increase the expression of the SMA protein.
Assuntos
Progressão da Doença , Insuficiência Respiratória , Atrofias Musculares Espinais da Infância , Argentina/epidemiologia , Estudos de Coortes , Hospitais Pediátricos , Humanos , Lactente , Respiração Artificial , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/mortalidade , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia , Atrofias Musculares Espinais da Infância/complicações , Atrofias Musculares Espinais da Infância/mortalidade , Atrofias Musculares Espinais da Infância/fisiopatologia , Atrofias Musculares Espinais da Infância/terapiaRESUMO
Latin America (LA) has a population of ~645 million people distributed over 33 countries with marked political, cultural and economic differences. In LA, patients with inherited neuromuscular diseases (NMDs) often do not have access to specialized medical centers and many of them go undiagnosed. General management and care of spinal muscular dystrophy (SMA) patients in the region varies due to heterogeneous health care. An active generation of young clinical neurologists is being trained for the specialized care of SMA and other neuromuscular (NM) patients, both in the private and public sectors. The Euro-Latin-American Summer School of Myology (EVELAM) as well as efforts of professionals at large public centers in the major cities of LA have a leading role in this development. Different regional academic-scientific organizations as well as the expanding number of telethon centers and the creation of parent organizations, mostly concerning SMA, all together are contributing to the increased quality of the management of NMD patients. Over the past years, academic and clinical research, as well as the establishment of qualified centers for the molecular testing of NMD are pushing forward the creation of patient registries and the development of specific clinical trials, with Argentina and Brazil having a major role in this field. Nevertheless, increased awareness and further training of specialized health professionals are necessary to reach patients that are currently lacking care throughout the region.
Assuntos
Gerenciamento Clínico , Atrofia Muscular Espinal/terapia , Sistema de Registros , Ensaios Clínicos como Assunto , Humanos , América Latina , Atrofia Muscular Espinal/epidemiologia , Participação do PacienteRESUMO
Objetivo: Describir el espectro clínico de pacientes con diagnóstico definitivo de Enfermedad Mitocondrial, y su correlación con hallazgos bioquímicos, neuroimagenológicos, neuropatológicos, y moleculares. Método: Se revisaron las historias clínicas de pacientes con Enfermedad Mitocondrial evaluados durante el período 1990-2011. Resultados: Se incluyeron 41 pacientes, con una edad media inicial de 3,7 años. Identificamos cuatro grupos:1) Síndromes clásicos (65%): a) MELAS del inglés Mitochondrial encephalomyopathy, lacticacidosis, and stroke-like episodes, (diez), b) Síndrome de Leigh (diez) c) Síndrome de Kearns Sayre (cinco), d) PEO del inglés Progressive External Ophthalmoplegia plus (OEP plus) (dos), 2) Miopatía: nueve (21,5%) 3) Encefalomiopatías inespecíficas: cinco (12%). Se realizó biopsia muscular en 37 pacientes. Un 70% evidenció fibras rojo rasgadas, cuatro (10,5%) fibras citocromo oxidasa negativas y ocho (14,7%) incremento de la actividad oxidativa subsarcolemal y en la microscopia electrónica alteraciones del tamaño y número de mitocondrias. En 14 se completaron estudios moleculares: Siete presentaron una mutación puntual A3243G en el ADN mitocondrial (MELAS), un paciente una mutación en el ADN mitocondrial A1351G (Síndrome de Leigh) y un paciente una deleción del ADN mitocondrial (OEP plus). Conclusiones: Se pudo corroborar la existencia en nuestro medio de síndromes asociados a patología mitocondrial tradicionalmente reconocidos. Un grupo de pacientes con encefalomiopatías denominadas inespecíficas presentaron un cuadro clínico variable, hallazgos de laboratorio y de imágenes poco orientadores y fue la sospecha de una enfermedad mitocondrial lo que nos llevó a realizar la biopsia que finalmente fue diagnóstica. Es posible que este grupo sea más numeroso y las limitaciones que implica realizar una biopsia muscular se facilite con los estudios moleculares.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Doença de Leigh/diagnóstico , Doença de Leigh/etiologia , Doenças Mitocondriais/classificação , Doenças Mitocondriais/complicações , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/patologia , Doenças Mitocondriais , Síndrome MELAS/diagnóstico , Síndrome MELAS/etiologia , Argentina , Encefalopatias/diagnóstico , Encefalopatias/etiologia , Oftalmoplegia Externa Progressiva Crônica/diagnóstico , Oftalmoplegia Externa Progressiva Crônica/etiologiaRESUMO
Objetivo: Describir el espectro clínico de pacientes con diagnóstico definitivo de Enfermedad Mitocondrial, y su correlación con hallazgos bioquímicos, neuroimagenológicos, neuropatológicos, y moleculares. Método: Se revisaron las historias clínicas de pacientes con Enfermedad Mitocondrial evaluados durante el período 1990-2011. Resultados: Se incluyeron 41 pacientes, con una edad media inicial de 3,7 años. Identificamos cuatro grupos:1) Síndromes clásicos (65%): a) MELAS del inglés ôMitochondrial encephalomyopathy, lacticacidosis, and stroke-like episodesö, (diez), b) Síndrome de Leigh (diez) c) Síndrome de Kearns ûSayre (cinco), d) PEO del inglés ôProgressive External Ophthalmoplegiaö plus (OEP plus) (dos), 2) Miopatía: nueve (21,5%) 3) Encefalomiopatías inespecíficas: cinco (12%). Se realizó biopsia muscular en 37 pacientes. Un 70% evidenció fibras rojo rasgadas, cuatro (10,5%) fibras citocromo oxidasa negativas y ocho (14,7%) incremento de la actividad oxidativa subsarcolemal y en la microscopia electrónica alteraciones del tamaño y número de mitocondrias. En 14 se completaron estudios moleculares: Siete presentaron una mutación puntual A3243G en el ADN mitocondrial (MELAS), un paciente una mutación en el ADN mitocondrial A1351G (Síndrome de Leigh) y un paciente una deleción del ADN mitocondrial (OEP plus). Conclusiones: Se pudo corroborar la existencia en nuestro medio de síndromes asociados a patología mitocondrial tradicionalmente reconocidos. Un grupo de pacientes con encefalomiopatías denominadas inespecíficas presentaron un cuadro clínico variable, hallazgos de laboratorio y de imágenes poco orientadores y fue la sospecha de una enfermedad mitocondrial lo que nos llevó a realizar la biopsia que finalmente fue diagnóstica. Es posible que este grupo sea más numeroso y las limitaciones que implica realizar una biopsia muscular se facilite con los estudios moleculares
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Doença de Leigh/diagnóstico , Doença de Leigh/etiologia , Oftalmoplegia Externa Progressiva Crônica/diagnóstico , Oftalmoplegia Externa Progressiva Crônica/etiologia , ArgentinaRESUMO
AIMS: In this paper we describe the clinical characteristics, and particularly the epileptic seizures and electroencephalographic findings, in 15 patients with a pathology diagnosis of late infantile neuronal ceroid lipofuscinosis (NCL). PATIENTS AND METHODS: Nine female and six male patients were studied and their clinical records covering the period February 1990 to June 2003 were analysed. Neuroimaging, neurometabolic studies, ERG, PE and repeated EEG were carried out in all cases. RESULTS: The mean age on onset of the disease was 3 years (range: 1-5 years). The initial symptom was epilepsy in all cases. Massive myoclonias and myoclonic-atonic seizures were the most frequent kinds of attacks. Focal myoclonias were observed in six patients. Other types of epileptic seizures observed included generalised tonic-clonic, absence, motor focal and complex focal. The epileptic seizures were resistant to therapy. Progressive neurological and visual impairment, pyramidal and cerebellar signs, as well as mental retardation were present in all cases. Intercritical EEG recordings showed diffuse paroxysms with spike and polyspike waves, multifocal spikes and, less often, focal spikes that were predominant in posterior regions. Photostimulation showed high amplitude (300-450) occipital spikes during the application of light stimulation between 1 and 8 Hz. ERG, VEP and SSEP results were pathological. Images showed signs of brain and cerebellar atrophy. Seven of the patients died between 8.5 and 11 years of age. CONCLUSIONS: Late infantile NCL must be considered in the case of a child aged between 1 and 5 years who presents seizures that are predominantly generalised myoclonias and myoclonic-atonic, in association with progressive neurological deterioration including pyramidal, cerebellar and visual signs and an EEG trace showing occipital paroxysms triggered by low frequency photostimulation.
Assuntos
Epilepsias Mioclônicas/fisiopatologia , Lipofuscinoses Ceroides Neuronais/fisiopatologia , Criança , Pré-Escolar , Eletroencefalografia , Eletrorretinografia , Epilepsias Mioclônicas/diagnóstico , Epilepsias Mioclônicas/etiologia , Feminino , Humanos , Lactente , Masculino , Lipofuscinoses Ceroides Neuronais/complicações , Lipofuscinoses Ceroides Neuronais/diagnóstico , Lipofuscinoses Ceroides Neuronais/genética , Estudos RetrospectivosAssuntos
Humanos , Masculino , Criança , Hipóxia Encefálica/diagnóstico , Hipóxia Encefálica/terapia , PediatriaRESUMO
INTRODUCTION: We analyze the clinical, neurological, EEG, neuroradiological features and evolution of two patients with subacute measles encephalitis. CASE REPORTS: The patients, aged five years and eleven months respectively showed an acute, progressive neurological compromise and deterioration of consciousness, epilepsia partialis continua and progressive damage on neuroimaging, with a history of measles in the first case and exposure to the virus in the second. The first patient had Hodgkin's disease and the other had a familial C4 deficit disorder. Fundoscopic examination showed lesions on the retina. The EEG showed unilateral slow waves and spikes. Brain CT and MRI revealed progressive cerebral atrophy and a unilateral corticosubcortical lesion. Measles antibodies in CSF were found in the first child and oligoclonal bands in the second. Our first patient died after three months and the second has a severe neurological damage. CONCLUSION: In immunocompromised patients with the exposure to a history of measles, acute neurological compromised and deterioration of consciousness, epilepsia partialis continua and progressive damage on neuroimaging, subacute measles encephalitis should be considered.
Assuntos
Encefalite Viral/complicações , Epilepsia/etiologia , Sarampo/complicações , Doença Aguda , Pré-Escolar , Encefalite Viral/diagnóstico , Feminino , Humanos , Masculino , Sarampo/diagnóstico , Fatores de TempoRESUMO
CASE REPORTS: We report a clinical and EEG study of 8 children with reflex myoclonic epilepsy of infancy to further confirm the existence of this syndrome first described by Ricci et al in 1995. RESULTS: Between February 1990 to July 2002, we identified 64 epileptic patients with myoclonic seizures with an onset in the first six years of life. Eight (12.5%) of these patients had myoclonic seizure stimuli sensible. The seizures were characterized by generalized, myoclonic jerks triggered by tactile stimuli in six patients and acoustic stimuli in two, in one of them myoclonic jerks were triggered by both types of stimuli. The seizures appeared between 5 and 20 months of age. Two of the 8 patients had spontaneous myoclonic attacks during sleep. Interictal EEG was normal during wakefulness and occasional discharges were evident during sleep. In contrast, the ictal EEG during both wakefulness and sleep showed generalized spike wave and polyspike slow wave paroxysms. Neurologic examination, neuroimaging and neurometabolic studies were normal. Myoclonic jerks disappeared in 6 patients after valproic acid administration and in two after clobazan administration. Antiepileptic treatment was discontinued in 6 patients and no seizure recurrence was observed during a median follow up of 6 years. CONCLUSION: Our patients presented electro clinical criteria compatible with the syndrome of reflex myoclonic epilepsy of infancy. This syndrome could be considered to be a new reflex epileptic syndrome or a variant of benign myoclonic epilepsy in infancy.