Síndrome opsoclono-mioclono: características clínicas, aspectos terapéuticos y factores pronósticos en una cohorte pediátrica española / Opsoclonus-myoclonus syndrome: clinical characteristics, therapeutic considerations, and prognostic factors in a Spanish paediatric cohort

Introducción: El síndrome opsoclono-mioclono-ataxia es un raro trastorno de inicio pediátrico; de base neuroinflamatoria y origen paraneoplásico, parainfeccioso o idiopático. Actualmente no hay biomarcadores, siendo el diagnóstico clínico. El pronóstico cognitivo parece estar relacionado con el inicio temprano de la terapia inmunomoduladora.MétodoSe describen las características epidemiológicas, clínicas, terapéuticas y pronósticas a largo plazo de una cohorte de 20 pacientes españoles.ResultadosLa edad media de debut fue de 21 meses (2-59 meses). La ataxia y el opsoclonus fueron los síntomas de inicio más frecuentes y predominantes en la evolución. El tiempo medio desde los primeros síntomas hasta el diagnóstico fue de 1,1 mes. Un tumor de extirpe neuroblástica fue detectado en el 45%, realizándose resección quirúrgica en siete y quimioterapia en dos pacientes. En el estudio de líquido cefalorraquídeo se constató pleocitosis en cuatro (25%), con negatividad de anticuerpos antineuronales y bandas oligoclonales en todos los casos estudiados. En el 100% se emplearon fármacos inmunomoduladores. En nueve pacientes el tratamiento combinado inmunomodulador se inició desde el momento del diagnóstico, y en cinco el tiempo medio de implementación fue de 2,2 meses. A largo plazo, seis de 10 pacientes con seguimiento superior a cinco años presentaban secuelas cognitivas leves o moderadas; cuatro pacientes presentaron recaídas, generalmente coincidiendo con el descenso de la corticoterapia.ConclusionesEl inicio precoz de la inmunoterapia, así como de la triple terapia en los casos que lo precisaron, se relacionó con una menor frecuencia de afectación cognitiva a los dos años del debut. (AU)

Introduction: Opsoclonus-myoclonus-ataxia syndrome is a rare neuroinflammatory disorder with onset during childhood; aetiology may be paraneoplastic, para-infectious, or idiopathic. No biomarkers have yet been identified, and diagnosis is clinical. Better cognitive prognosis appears to be related to early onset of immunomodulatory therapy.MethodsWe describe the epidemiological, clinical, therapeutic, and long-term prognostic characteristics of a cohort of 20 Spanish patients.ResultsThe mean age of onset was 21 months (range, 2-59). Ataxia and opsoclonus were the most frequent symptoms both at disease onset and throughout disease progression. The mean time from onset to diagnosis was 1.1 months. Neuroblast lineage tumours were detected in 45% of patients; these were treated with surgical resection in 7 cases and chemotherapy in 2. Cerebrospinal fluid analysis revealed pleocytosis in 4 cases (25%) and neither antineuronal antibodies nor oligoclonal bands were detected in any patient. Immunomodulatory drugs were used in all cases. Nine patients started combined immunomodulatory treatment at the time of diagnosis, and 5 patients after a mean of 2.2 months. In the long term, 6 of the 10 patients followed up for more than 5 years presented mild or moderate cognitive sequelae. Four patients presented relapses, generally coinciding with the decrease of corticosteroid doses.ConclusionsEarly initiation of immunotherapy, as well as triple combination therapy, where needed, was associated with a lower frequency of cognitive impairment 2 years after onset. (AU)

Opsoclonus-myoclonus syndrome: Clinical characteristics, therapeutic considerations, and prognostic factors in a Spanish paediatric cohort.

INTRODUCTION: Opsoclonus-myoclonus-ataxia syndrome is a rare neuroinflammatory disorder with onset during childhood; aetiology may be paraneoplastic, para-infectious, or idiopathic. No biomarkers have yet been identified, and diagnosis is clinical. Better cognitive prognosis appears to be related to early onset of immunomodulatory therapy. METHODS: We describe the epidemiological, clinical, therapeutic, and long-term prognostic characteristics of a cohort of 20 Spanish patients. RESULTS: The mean age of onset was 21 months (range, 2-59). Ataxia and opsoclonus were the most frequent symptoms both at disease onset and throughout disease progression. The mean time from onset to diagnosis was 1.1 months. Neuroblast lineage tumours were detected in 45% of patients; these were treated with surgical resection in 7 cases and chemotherapy in 2. Cerebrospinal fluid analysis revealed pleocytosis in 4 cases (25%) and neither antineuronal antibodies nor oligoclonal bands were detected in any patient. Immunomodulatory drugs were used in all cases. Nine patients started combined immunomodulatory treatment at the time of diagnosis, and 5 patients after a mean of 2.2 months. In the long term, 6 of the 10 patients followed up for more than 5 years presented mild or moderate cognitive sequelae. Four patients presented relapses, generally coinciding with the decrease of corticosteroid doses. CONCLUSIONS: Early initiation of immunotherapy, as well as triple combination therapy, where needed, was associated with a lower frequency of cognitive impairment 2 years after onset.

Opsoclonus-myoclonus syndrome: clinical characteristics, therapeutic considerations, and prognostic factors in a Spanish paediatric cohort. / Síndrome opsoclono-mioclono: características clínicas, aspectos terapéuticos y factores pronósticos en una cohorte pediátrica española.

INTRODUCTION: Opsoclonus-myoclonus-ataxia syndrome is a rare neuroinflammatory disorder with onset during childhood; aetiology may be paraneoplastic, para-infectious, or idiopathic. No biomarkers have yet been identified, and diagnosis is clinical. Better cognitive prognosis appears to be related to early onset of immunomodulatory therapy. METHODS: We describe the epidemiological, clinical, therapeutic, and long-term prognostic characteristics of a cohort of 20 Spanish patients. RESULTS: The mean age of onset was 21 months (range, 2-59). Ataxia and opsoclonus were the most frequent symptoms both at disease onset and throughout disease progression. The mean time from onset to diagnosis was 1.1 months. Neuroblast lineage tumours were detected in 45% of patients; these were treated with surgical resection in 7 cases and chemotherapy in 2. Cerebrospinal fluid analysis revealed pleocytosis in 4 cases (25%) and neither antineuronal antibodies nor oligoclonal bands were detected in any patient. Immunomodulatory drugs were used in all cases. Nine patients started combined immunomodulatory treatment at the time of diagnosis, and 5 patients after a mean of 2.2 months. In the long term, 6 of the 10 patients followed up for more than 5 years presented mild or moderate cognitive sequelae. Four patients presented relapses, generally coinciding with the decrease of corticosteroid doses. CONCLUSIONS: Early initiation of immunotherapy, as well as triple combination therapy, where needed, was associated with a lower frequency of cognitive impairment 2 years after onset.

Déficit de carnitina palmitoil transferasa II: peculiaridades en su diagnóstico / Rhabdomyolysis due to carnitine palmitoyl transferase II deficiency

Introducción: El déficit de carnitina palmitoil transferasa II (CPT-II) es la miopatía metabólica más frecuente causante de crisis recurrentes de rabdomiólisis en la infancia, especialmente después del ejercicio. Caso clínico: Niño de 13 años que consulta por dolor muscular y orinas oscuras tras haber realizado ejercicio físico intenso. Como antecedentes personales destaca un episodio hace un año de similares características. Los hallazgos analíticos más relevantes fueron: CPK 283.400 UI/L [38-190], AST 4.178 UI/L [5-35], ALT 768 UI/L [5-26], LDH 4.100 UI/L [135-225] y mioglobinuria 17.446 µg/24 horas, con resto de parámetros analíticos dentro de la normalidad. Se realiza estudio metabólico en sangre y orina incluyendo: ácidos orgánicos, carnitina, acilcarnitinas, piruvato y lactato sin hallazgos patológicos. Ante la alta sospecha clínica y a pesar de la normalidad del estudio metabólico, se solicita estudio del gen de la CPT-II, encontrando la mutación c338C>T en homocigosis en dicho gen, lo cual confirma el diagnóstico. Conclusiones: El déficit de CPT-II es la causa más frecuente de rabdomiólisis recurrente en la infancia dentro de las miopatías metabólicas. Para su diagnóstico es fundamental una alta sospecha clínica. Los estudios que confirman el diagnóstico son el análisis genético o la medición de la actividad enzimática en músculo, a pesar de un estudio metabólico normal. Las medidas higiénico-dietéticas, evitando los periodos de ayuno y siguiendo una dieta rica en hidratos de carbono de absorción lenta permiten a estos niños llevar a cabo una vida normal

Introduction: Carnitine palmitoyl transferase II deficiency (CPT-II) is the most common inherited cause of recurrent episodes of rhabdomyolysis in childhood, especially after exertion. Case report: 13 year-old child with dark urine and myalgia after prolonged exercise. His medical history included a similar event a year ago. The main laboratory findings were: CPK 283,400 IU / L [38-190], AST 4,178 IU / L [5-35], ALT 768 IU / L. [5-26], LDH 4100 IU / L [135-225] and myoglobinuria 17,446 µg / 24 hours. Metabolic study in plasma and urine was performed including: organic acids, carnitine, acylcarnitines, pyruvate and lactate without abnormal findings. Given the high clinical suspicion and despite normal metabolic study, study of gene CPT-II is requested showing c338C>T homozygous mutation which confirms the diagnosis. Conclusions: CPT-II deficiency is the most common cause of recurrent episodes of rhabdomyolysis in childhood. High clinical suspicion is the main factor in the diagnostic process. Genetic analysis or enzyme activity measurement in muscle will confirm the diagnosis despite normal metabolic studies in plasma and urine. Treatment consists of nutritional modifications including avoidance of fasting and a high slow burning carbohydrates diet