Tratamiento con TRIAC en pacientes pediátricos con deficiencia de MCT8 / Treatment with TRIAC in pediatric patients with MCT8

Los transportadores de monocarboxilatos (MCT) permiten el ingreso celular de hormonas tiroideas, especialmente en el sistema nervioso central (SNC), donde son indispensables para el neurodesarrollo. La deficiencia de MCT8 produce la combinación de hipotiroidismo en SNC e hipertiroidismo periférico, caracterizada por T3 elevada. El único tratamiento actualmente disponible es el ácido 3,3',5-triyodotiroacético (TRIAC), un análogo de hormonas tiroideas que tiene como objetivo mejorar la tirotoxicosis periférica y prevenir la progresión del deterioro neurológico. En el presente artículo, se evalúan las características clínicas, imagenológicas, bioquímicas y genéticas de 4 pacientes con deficiencia de MCT8 tratados con TRIAC hasta la fecha, las dosis utilizadas y la respuesta al tratamiento.

Monocarboxylate transporters (MCTs) allow the cellular entry of thyroid hormones, especially into the central nervous system (CNS), where they are crucial for neurodevelopment. MCT8 deficiency results in the combination of hypothyroidism in the CNS and peripheral hyperthyroidism, characterized by elevated T3 levels. The only treatment currently available is 3,3',5-triiodothyroacetic acid (TRIAC), a thyroid hormone analogue aimed at improving peripheral thyrotoxicosis and preventing the progression of neurological impairment. Here we assess the clinical, imaging, biochemical, and genetic characteristics of 4 patients with MCT8 deficiency who have received TRIAC to date, the doses used, and the response to treatment.

Population Pharmacodynamic Modelling of the CD19+ Suppression Effects of Rituximab in Paediatric Patients with Neurological and Autoimmune Diseases.

BACKGROUND: Limited pharmacotherapy and the failure of conventional treatments in complex pathologies in children lead to increased off-label use of rituximab. We aimed to characterize the time course of CD19+ B lymphocytes (CD19+) under treatment with intravenous rituximab in children with neurologic and autoimmune diseases and to evaluate the impact of covariates (i.e., demographics, diagnosis and substitution between innovator and biosimilar product) on rituximab pharmacodynamics and disease activity. METHODS: Pre- and post-drug infusion CD19+ in peripheral blood were prospectively registered. A population pharmacodynamic model describing the time course of CD19+ was developed with NONMEM v7.4. Simulations of three different rituximab regimens were performed to assess the impact on CD19+. Logistic regression analysis was performed to identify predictors of clinical response recorded through disease activity scores. RESULTS: 281 measurements of CD19+ lymphocyte counts obtained from 63 children with neurologic (n = 36) and autoimmune (n = 27) diseases were available. The time course of CD19+ was described with a turn-over model in which the balance between synthesis and degradation rates is disrupted by rituximab, increasing the latter process. The model predicts half-lives (percent coefficient of variation, CV(%)) of rituximab and CD19+ of 11.6 days (17%) and 173.3 days (22%), respectively. No statistically significant effect was found between any of the studied covariates and model parameters (p > 0.05). Simulations of different regimens showed no clinically significant differences in terms of CD19+ repopulation times. A trend towards a lack of clinical response was observed in patients with lower CD19+ repopulation times and higher areas under the CD19+ versus time curve. CONCLUSIONS: Rituximab pharmacodynamics was described in a real-world setting in children suffering from autoimmune and neurologic diseases. Diagnosis, substitution between innovator rituximab and its biosimilars or type of regimen did not affect rituximab-induced depletion of CD19+ nor the clinical response in this cohort of patients. According to this study, rituximab frequency and dosage may be chosen based on clinical convenience or safety reasons without affecting CD19+ repopulation times. Further studies in larger populations are required to confirm these results.

Treatment with TRIAC in pediatric patients with MCT8. / Tratamiento con TRIAC en pacientes pediátricos con deficiencia de MCT8.

Monocarboxylate transporters (MCTs) allow the cellular entry of thyroid hormones, especially into the central nervous system (CNS), where they are crucial for neurodevelopment. MCT8 deficiency results in the combination of hypothyroidism in the CNS and peripheral hyperthyroidism, characterized by elevated T3 levels. The only treatment currently available is 3,3',5-triiodothyroacetic acid (TRIAC), a thyroid hormone analogue aimed at improving peripheral thyrotoxicosis and preventing the progression of neurological impairment. Here we assess the clinical, imaging, biochemical, and genetic characteristics of 4 patients with MCT8 deficiency who have received TRIAC to date, the doses used, and the response to treatment.

Los transportadores de monocarboxilatos (MCT) permiten el ingreso celular de hormonas tiroideas, especialmente en el sistema nervioso central (SNC), donde son indispensables para el neurodesarrollo. La deficiencia de MCT8 produce la combinación de hipotiroidismo en SNC e hipertiroidismo periférico, caracterizada por T3 elevada. El único tratamiento actualmente disponible es el ácido 3,3',5-triyodotiroacético (TRIAC), un análogo de hormonas tiroideas que tiene como objetivo mejorar la tirotoxicosis periférica y prevenir la progresión del deterioro neurológico. En el presente artículo, se evalúan las características clínicas, imagenológicas, bioquímicas y genéticas de 4 pacientes con deficiencia de MCT8 tratados con TRIAC hasta la fecha, las dosis utilizadas y la respuesta al tratamiento.

Intensive Safety Monitoring of Rituximab (Biosimilar Novex® and the Innovator) in Pediatric Patients With Complex Diseases.

Although rituximab is widely used off-label for complex pediatric diseases, safety reports are limited. We aimed to report evidence of its use in clinical practice, to describe the incidence of adverse drug reactions (ADR) to rituximab biosimilar Novex® and innovator, and to identify risk factors for the development of ADR in a real-life follow-up cohort of pediatric patients with complex diseases. We conducted a prospective, longitudinal, observational, single-centre study in patients that received rituximab for any complex disease, and as part of an intensive pharmacovigilance program. Demographic, pharmacological, clinical, and drug-related data were collected for all patients. ADR-free survival, including infusion-related reactions (IRR) and delayed ADR (dADR), was estimated using Kaplan-Meier curves. Risk factors were evaluated by multivariable Cox regression models. In total, 77 patients (<19 y.o.) received 187 infusions of rituximab Novex® (n = 155) or innovator rituximab (n = 32) for neurologic (Neu), immune-hematologic-rheumatic (IHR), oncologic (O) diseases, and hematopoietic stem-cell transplantation (HSCT) or solid-organ transplantation (SOT). We recorded 29 IRR and 58 dADR that occurred in 27 (35.1%) and 29 (37.7%) patients, respectively. The respiratory tract was the most affected during IRR (29.6%) and hypogammaglobulinemia (37.9 %) was the most frequent dADR. First versus subsequent infusions (HR 5.4, CI95% 2.4-12.1, p<0.05), sex (boys vs. girls, HR 0.3, CI95% 0.1-0.8, and p<0.05), and diagnosis (Neu-IHR diseases vs. O-HSCT-SOT, HR 2.3, CI95% 1.02-5.4, and p < 0.05) were significantly associated with the development of IRR. For dADR, risk factors were diagnosis (Neu-IHR diseases vs. O-HSCT-SOT, HR 0.4, CI95% 0.2-0.9, and p < 0.05) and cumulative body surface area-normalized dosage (HR 1.0003, CI95% 1.0001-1.0006, and p < 0.05). The present is the largest real-world safety assessment of rituximab in Latin-American children with complex diseases supporting its use based on the overall acceptable safety. Identification of risk factors may contribute to optimization of off-label rituximab treatment in pediatrics.

Prognostic indicators of improvement with therapeutic plasma exchange in pediatric demyelination.

OBJECTIVES: To determine the safety and clinical benefit of therapeutic plasma exchange (TPE) as rescue therapy in children with acute inflammatory demyelinating CNS syndromes and to identify baseline prognostic indicators of treatment improvement. METHODS: This single-center retrospective pediatric cohort included all consecutive patients admitted to our hospital over the period from 2003 to 2017 because of a steroid-refractory acute CNS event presumed to be inflammatory who required TPE. Functional status assessment to identify improvement included the following performance category scales: visual outcome, bladder control, gait, and Expanded Disability Status Scale (EDSS). These assessments were performed before and after TPE in every patient. RESULTS: Sixty-five children requiring TPE to treat 78 CNS attacks were included for analysis. Median age at TPE was 10.5 years (1.9-18 years); 45% were girls. Seropositivity (aquaporin-4 water channel-immunoglobulin G [IgG] or myelin oligodendrocyte glycoprotein-IgG) was found in 20 of 42 (48%) patients. Attack phenotypes leading to TPE were optic neuritis (ON) in 42%, longitudinally extensive transverse myelitis (LETM) in 31%, ON + LETM in 15%, and other combined syndromes in 11%. Overall, moderate to marked neurologic improvement was observed in 72% of children at the end of TPE and in 88.5% at 6 months of follow-up. Lower baseline scores on the EDSS, visual outcome, and gait scales were found to be independent prognostic indicators of treatment benefit. Sex, age at onset and at TPE, attack phenotype, disease duration, and time from attack onset to TPE initiation were not significantly associated with treatment outcome. Adverse events were observed in 31 of 524 (5.9%) procedures, being severe in 4. CONCLUSIONS: TPE was an effective rescue therapy associated with functional improvement. No therapeutic window for TPE initiation was identified in this pediatric cohort. Overall frequency of adverse events was low; however, serious events should be anticipated and avoided. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for children with acute inflammatory demyelinating CNS syndromes, TPE leads to functional improvement.

[Demyelinating disorders]. / Enfermedades desmielinizantes.

Demyelinating diseases are a group of conditions of autoimmune etiology directed against the myelin of the central nervous system. In many cases, the onset of the illness is preceded by a nonspecific viral infection. Multiple sclerosis is a disease that evolves with relapses and remissions with polyfocal neurological deficits, being the most frequent optic neuritis, transverse myelitis and encephalic trunk involvement. Typically, magnetic resonance image (MRI) shows peri-ventricular, peri-callosal, cerebellum, brain stem and spinal cord hyperintensive lesions in T2 and FLAIR weighted images. Optic neuromyelitis is characterized by the presence of optic neuritis and transverse myelitis associated with the postrema and diencephalic area syndrome. MRI lesions are distributed in sectors rich with aquaporine-4 channels (AQP-4): hypothalamus, third and fourth ventricle, optic nerves and spinal cord. Finding anti AQP4 antibodies is useful for the diagnosis although they are not essential for it. Acute disseminated encephalomyelitis is typically a monophasic condition characterized by acute encephalopathy associated with hyperintense MRI large, bilateral and irregular asymmetric lesion in T2 and FLAIR weighted images. In all three cases, cerebral spine fluid (CSF) can show pleocytosis and hyperproteinorrachia. The presence of oligoclonal bands in CSF is characteristic of multiple sclerosis. In all cases, acute treatment includes high dose intravenous corticosteroids and plasmapheresis in non-responsive cases. Both multiple sclerosis and optic neuromyelitis require long-term treatment to prevent relapse and recurrent diseases.

Enfermedades desmielinizantes / Demyelinating disorders

Las enfermedades desmielinizantes constituyen un grupo de afecciones de etiología autoinmune dirigida contra la mielina del sistema nervioso central. En muchos casos, el inicio del cuadro es precedido por una infección viral inespecífica. La esclerosis múltiple evoluciona con recaídas y remisiones con déficit neurológicos polifocales, siendo los más frecuentes la neuritis óptica, la mielitis transversa y el compromiso de tronco encefálico. Se caracteriza por lesiones hiperintensas que se observan en una resonancia magnética nuclear (RMN) en T2 y FLAIR peri-ventriculares y peri-callosas, cerebelo, tronco y médula espinal. La neuromielitis óptica se caracteriza por la presencia de neuritis óptica y mielitis transversa asociada a síndrome de área postrema y diencefálico. Las lesiones en RMN se distribuyen en los sectores ricos en acuaporina-4 (AQP-4): hipotálamo, peri tercer y cuarto ventrículo, nervios ópticos y médula espinal. Los anticuerpos anti AQP4 ayudan al diagnóstico aunque no son esenciales para el mismo. La encefalomielitis diseminada aguda es un cuadro clásicamente monofásico caracterizado por una encefalopatía aguda asociada a lesiones en RMN hiperintensas en T2 y FLAIR bilaterales, asimétricas, de gran tamaño y de bordes irregulares. En los tres casos, el líquido cefalorraquídeo (LCR) puede mostrar pleocitosis e hiperproteinorraquia. La presencia de bandas oligoclonales en LCR es característica de la esclerosis múltiple. En todos los casos, el tratamiento agudo incluye corticoides a altas dosis por vía endovenoso y en caso de no respuesta, plasmaféresis. Tanto la esclerosis múltiple como la neuromielitis óptica requieren tratamiento a largo plazo para evitar nuevas recaídas ya que se trata de enfermedades recurrentes.

Demyelinating diseases are a group of conditions of autoimmune etiology directed against the myelin of the central nervous system. In many cases, the onset of the illness is preceded by a nonspecific viral infection. Multiple sclerosis is a disease that evolves with relapses and remissions with polyfocal neurological deficits, being the most frequent optic neuritis, transverse myelitis and encephalic trunk involvement. Typically, magnetic resonance image (MRI) shows peri-ventricular, peri-callosal, cerebellum, brain stem and spinal cord hyperintensive lesions in T2 and FLAIR weighted images. Optic neuromyelitis is characterized by the presence of optic neuritis and transverse myelitis associated with the postrema and diencephalic area syndrome. MRI lesions are distributed in sectors rich with aquaporine-4 channels (AQP-4): hypothalamus, third and fourth ventricle, optic nerves and spinal cord. Finding anti AQP4 antibodies is useful for the diagnosis although they are not essential for it. Acute disseminated encephalomyelitis is typically a monophasic condition characterized by acute encephalopathy associated with hyperintense MRI large, bilateral and irregular asymmetric lesion in T2 and FLAIR weighted images. In all three cases, cerebral spine fluid (CSF) can show pleocytosis and hyperproteinorrachia. The presence of oligoclonal bands in CSF is characteristic of multiple sclerosis. In all cases, acute treatment includes high dose intravenous corticosteroids and plasmapheresis in non-responsive cases. Both multiple sclerosis and optic neuromyelitis require long-term treatment to prevent relapse and recurrent diseases.

Parálisis ácida aguda "polio-like" (Brote de 10 casos presentados en Buenos Aires - Argentina en 2016) / Acute acid paralysis "polio-like" (Outbreak of 10 cases presented in Buenos Aires - Argentina in 2016)

Resumen Objetivo Reportar un brote de 10 casos de mielopatías ácida aguda asimétrica por compromiso de la motoneurona espinal. Material y métodos: Relación V/M: 6/4 media de edad de 3 años, todos con parálisis ácida aguda, analizamos sus aspectos clínicos, etiológicos, neurorradiológicos, terapéuticos y evolutivos. Resultados: 8 presentaron parálisis áccida de miembros superiores asimétrica, 1 monoplejía de miembro inferior izquierdo, 1 hemiparesia, 5 sumaron compromiso de pares craneanos y 4 requirieron asistencia respiratoria mecánica. Todos coincidieron con catarro de vía aérea superior y/o ebre. La resonancia magnética medular fue anormal en todos, identi cando dos patrones de imágenes: uno lineal relacionado al compromiso del asta anterior y otro más heterogéneo con médula espinal engrosada, sin refuerzo con contraste, 5/10 presentaron además compromiso bulbo-protuberancial. Ninguno presento lesiones supratentoriales. En 4/10 identi camos enterovirus humano subtipo D68 HEV-D68) en secreciones de vía aérea y en 1/10 de ellos también en LCR. En el resto se detectaron otros enterovirus A, B y C, en uno rinovirus y otro In uenza. Nueve pacientes recibieron como tratamiento gammaglobulina y corticoides y 4 además recambio plasmático terapéutico sin mejoría clínica. Conclusiones: Ante una parálisis ácida aguda es importante descartar el HEV-D68. Consideramos los casos no detectados como "falsos negativos" dado que las muestras fueron tomadas tardíamente. Los otros virus identi cados no se han relacionado a mielopatías. Si bien la siopatología no es clara la ausencia de respuesta a tratamiento antin amatorio e inmunomodulador orienta a un mecanismo de agresión directa del virus. Se trata del primer reporte por HEV-D68 en Latinoamérica.

Abstract Objective: To report an outbreak of 10 cases of acute asymmetric accid myelopathy due to spinal motor neuron injury. Material and methods: Ten children, six male, with a mean age of 3 years presented with acute accid myelitis. We analyzed clinical features, etiology, neuroradiological images, treatment, and outcome. Results: Eight children had bilateral and asymmetric accid myelitis of the upper limbs, 1 had upper limb monoplegia, and 1 presented with hemiparesis. The cranial nerves were involved in 5 patients and 4 required mechanical ventilation. In all cases acute accid myelitis co-occurred with upper airway infection and/or fever. Spinal cord magnetic resonance imaging was abnormal in all, showing 2 di erent patterns: A linear pattern involving the anterior horns and another that was more heterogeneous showing spinal cord expansion. The lesions were non-enhancing in all. In 5/10 patients involvement of the medulla oblongata and pons was also observed. None of the patients presented with supratentorial lesions. In 4/10 children, the human enterovirus subtype D68 (HEV-D68) was identi ed in the airway and in 1/10 in the cerebrospinal uid as well. In the remaining patients di erent enterovirus species A, B, and C variants were detected, as well as rhinovirus in 1 and in uenza in another. Nine children received treatment with intravenous immunoglobulin and steroids and 4 of these children also underwent plasma exchange. Treatment did not lead to clinical improvement. Conclusions: In a patient with acute accid myelitis, HEV-D68 infection should be ruled out. Cases in which the virus was not detected were considered as "false negatives" as samples were collected late in course of the disease. The lack of response to anti-in ammatory and immunomodulatory treatment suggests a direct viral mechanism. This study is to our knowledge the rst on an HEV-D68-infection-related report in Latin America.

Aumento inusual de casos de mielitis en un hospital pediátrico en Argentina / Unusual increase of cases of myelitis in a pediatric hospital in Argentina

Introducción: La asociación entre enterovirus D68 y cuadros de mielitis aguda fláccida ha sido descrita en Estados Unidos, en 2014. Desde ese año, se han reportado casos esporádicamente en Canadá y Europa. Se describe, en este estudio, una serie de casos con mielitis aguda fláccida en el Hospital de Pediatría "Prof. Dr. Juan P. Garrahan" en Buenos Aires, Argentina, en 2016. Métodos: Estudio descriptivo, retrospectivo. Se incluyeron todos los pacientes internados desde el 1/04/2016 al 1/07/2016 con mielitis fláccida aguda con lesiones en la médula espinal que comprometieran la sustancia gris en la resonancia magnética nuclear. Se procesaron, para la búsqueda etiológica, muestras de secreciones nasofaríngeas, hisopados de materia fecal y líquido cefalorraquídeo. Resultados: Se incluyeron 10 pacientes. La mediana de edad fue 4 años (rango de 3 meses a 5 años). Ocho pacientes tuvieron una enfermedad febril autolimitada antes del inicio de los síntomas neurológicos. Los hallazgos neurológicos fueron debilidad fláccida de, al menos, un miembro, cervicoplejia (n= 2) y parálisis facial (n= 2). Todos los pacientes presentaron lesiones longitudinales en la médula espinal, con compromiso de sustancia gris, predominantemente, en el asta anterior. En todos los casos, se realizó una punción lumbar. En 7 pacientes, se observó pleocitosis. En cuatro niños, se identificó enterovirus D68 en secreciones nasofaríngeas y, en uno, se identificó el enterovirusD68 en el líquido cefalorraquídeo. Todos los pacientes persistieron con déficits neurológicos al momento del alta. Conclusiones: Se reporta el primer brote de mielitis aguda fláccida asociada a enterovirusD68 en Argentina. La vigilancia epidemiológica activa permitirá conocer la verdadera incidencia, epidemiología y etiología de esta enfermedad.

Introduction: The association between enterovirus D68 and acute flaccid myelitis was first described in the United States in 2014. Since then, sporadic cases have been reported in Canada and Europe. This study describes a series of cases of acute flaccid myelitis at Hospital de Pediatría "Prof. Dr. Juan P. Garrahan," in Buenos Aires, Argentina, during 2016. Methods: Descriptive, retrospective study. All patients with acute flaccid myelitis and lesions in the spinal cord involving the gray matter, as observed in the magnetic resonance imaging (MRI) scan, hospitalized from 04/01/2016 to 07/01/2016, were included in the study. Samples of nasopharyngeal secretions, fecal swabs and cerebrospinal fluid were collected and processed to look for the causative agent. Results: Ten patients were included. The median age was 4 years old (range from 3 months to 5 years old). Eight patients had a self-limiting febrile condition before the onset of neurological symptoms. Neurological findings were flaccid weakness in, at least, one limb, cervical paralysis (n= 2) and facial paralysis (n= 2). All patients had longitudinal lesions in the spinal cord, with gray matter involvement, mainly in the anterior horn. In all cases, a lumbar puncture (spinal tap) was performed. Pleocytosis was observed in 7 patients. In four children, enterovirus D68 was identified in nasopharyngeal secretions, and in one, it was detected in the cerebrospinal fluid. Neurological deficit persisted in all patients at the time of discharge. Conclusions: The first outbreak of acute flaccid myelitis associated to enterovirus D68 is reported in Argentina. Active epidemiological surveillance will help to determine the true incidence, epidemiology and etiology of this disease.

Enterovirus D68 infection in a cluster of children with acute flaccid myelitis, Buenos Aires, Argentina, 2016.

OBJECTIVE: To report a outbreak of 11 cases of acute asymmetric flaccid myelopathy due to spinal motor neuron injury. MATERIAL AND METHODS: Eleven children, six male, with a mean age of 3 years presented with acute flaccid myelitis. We analyzed clinical features, etiology, neuroradiological images, treatment, and outcome. RESULTS: Nine children had bilateral and asymmetric flaccid myelitis of the upper limbs, 1 had upper limb monoplegia, and 1 presented with hemiparesis. The cranial nerves were involved in 6 patients and 4 required mechanical ventilation. In all cases acute flaccid myelitis co-occurred with upper airway infection and/or fever. Spinal cord magnetic resonance imaging was abnormal in all, showing 2 different patterns: A linear pattern involving the anterior horns and another that was more heterogeneous showing spinal cord expansion. The lesions were non-enhancing in all. In 5/11 patients involvement of the medulla oblongata and pons was also observed. None of the patients presented with supratentorial lesions. In 4/11 children, the human enterovirus subtype D68 (HEV-D68) was identified in the airway and in 1/11 in the cerebrospinal fluid as well. In the remaining patients different enterovirus species A, B, and C variants were detected, as well as rhinovirus in 1 and influenza in another. Ten children received treatment with intravenous immunoglobulin and steroids and 4 of these children also underwent plasma exchange. Treatment did not lead to clinical improvement. CONCLUSIONS: In a patient with acute flaccid myelitis, HEV-D68 infection should be ruled out. Cases in which the virus was not detected were considered as "false negatives" as samples were collected late in course of the disease. The lack of response to anti-inflammatory and immunomodulatory treatment suggests a direct viral mechanism. This study is to our knowledge the first on an HEV-D68-infection-related cluster in Latin America.

Unusual increase of cases of myelitis in a pediatric hospital in Argentina. / Aumento inusual de casos de mielitis en un hospital pediátrico en Argentina.

INTRODUCTION: The association between enterovirus D68 and acute flaccid myelitis was first described in the United States in 2014. Since then, sporadic cases have been reported in Canada and Europe. This study describes a series of cases of acute flaccid myelitis at Hospital de Pediatría "Prof. Dr. Juan P. Garrahan," in Buenos Aires, Argentina, during 2016. METHODS: Descriptive, retrospective study. All patients with acute flaccid myelitis and lesions in the spinal cord involving the gray matter, as observed in the magnetic resonance imaging (MRI) scan, hospitalized from 04/01/2016 to 07/01/2016, were included in the study. Samples of nasopharyngeal secretions, fecal swabs and cerebrospinal fluid were collected and processed to look for the causative agent. RESULTS: Ten patients were included. The median age was 4 years old (range from 3 months to 5 years old). Eight patients had a self-limiting febrile condition before the onset of neurological symptoms. Neurological findings were flaccid weakness in, at least, one limb, cervical paralysis (n= 2) and facial paralysis (n= 2). All patients had longitudinal lesions in the spinal cord, with gray matter involvement, mainly in the anterior horn. In all cases, a lumbar puncture (spinal tap) was performed. Pleocytosis was observed in 7 patients. In four children, enterovirus D68 was identified in nasopharyngeal secretions, and in one, it was detected in the cerebrospinal fluid. Neurological deficit persisted in all patients at the time of discharge. CONCLUSIONS: The first outbreak of acute flaccid myelitis associated to enterovirus D68 is reported in Argentina. Active epidemiological surveillance will help to determine the true incidence, epidemiology and etiology of this disease.

INTRODUCCIÓN: La asociación entre enterovirus D68 y cuadros de mielitis aguda fláccida ha sido descrita en Estados Unidos, en 2014. Desde ese año, se han reportado casos esporádicamente en Canadá y Europa. Se describe, en este estudio, una serie de casos con mielitis aguda fláccida en el Hospital de Pediatría "Prof. Dr. Juan P. Garrahan" en Buenos Aires, Argentina, en 2016. MÉTODOS: Estudio descriptivo, retrospectivo. Se incluyeron todos los pacientes internados desde el 1/04/2016 al 1/07/2016 con mielitis fláccida aguda con lesiones en la médula espinal que comprometieran la sustancia gris en la resonancia magnética nuclear. Se procesaron, para la búsqueda etiológica, muestras de secreciones nasofaríngeas, hisopados de materia fecal y líquido cefalorraquídeo. RESULTADOS: Se incluyeron 10 pacientes. La mediana de edad fue 4 años (rango de 3 meses a 5 años). Ocho pacientes tuvieron una enfermedad febril autolimitada antes del inicio de los síntomas neurológicos. Los hallazgos neurológicos fueron debilidad fláccida de, al menos, un miembro, cervicoplejia (n= 2) y parálisis facial (n= 2). Todos los pacientes presentaron lesiones longitudinales en la médula espinal, con compromiso de sustancia gris, predominantemente, en el asta anterior. En todos los casos, se realizó una punción lumbar. En 7 pacientes, se observó pleocitosis. En cuatro niños, se identificó enterovirus D68 en secreciones nasofaríngeas y, en uno, se identificó el enterovirusD68 en el líquido cefalorraquídeo. Todos los pacientes persistieron con déficits neurológicos al momento del alta. CONCLUSIONES: Se reporta el primer brote de mielitis aguda fláccida asociada a enterovirusD68 en Argentina. La vigilancia epidemiológica activa permitirá conocer la verdadera incidencia, epidemiología y etiología de esta enfermedad.